Page last updated: 2024-10-15

cyclic gmp

Description

Cyclic GMP: Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed) [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

3',5'-cyclic GMP : A 3',5'-cyclic purine nucleotide in which the purine nucleobase is specified as guanidine. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID135398570
CHEMBL ID395336
CHEBI ID16356
SCHEMBL ID738
SCHEMBL ID19222127
MeSH IDM0009685

Synonyms (65)

Synonym
2-amino-9-[(1s,6r,8r,9r)-3,9-dihydroxy-3-oxo-2,4,7-trioxa-3$l^{5}-phosphabicyclo[4.3.0]nonan-8-yl]-3h-purin-6-one
3',5'-guanosine monophosphate
gtpl2347
guanosine-3',5'-monophosphate
cmc_11906
guanosine 3',5'-phosphate
guanosine cyclic 3',5'-phosphate
guanosine 3',5'-phosphate (cyclic)
guanosine 3',5'-monophosphate
6h-purin-6-one, 2-amino-3,9-dihydro-9-[(4ar,6r,7r,7as)-tetrahydro-2,7-dihydroxy-2-oxido-4h-furo[3,2-d]-1,3,2-dioxaphosphorin-6-yl]-
cmc_11907
guanosine, cyclic 3',5'-(hydrogen phosphate)
35g ,
4h-furo[3,2-d]-1,3,2-dioxaphosphorin, guanosine deriv.
cyclic guanosine 3',5'-monophosphate
guanosine cyclic monophosphate
3',5'-gmp
cyclic guanosine monophosphate
cyclic 3',5'-guanylic acid
cyclic 3',5'-gmp
CHEBI:16356 ,
guanosine 3',5'-(hydrogen phosphate)
3',5'-cyclic gmp
7665-99-8
cyclic gmp
guanosine 3',5'-cyclic phosphate
guanosine-cyclic-phosphoric-acid
C00942
cyclic-gmp
CGMP ,
guanosine 3',5'-cyclic-monophosphate
DB02315
caged cgmp
gmp, cyclic
2-amino-9-[(4ar,6r,7r,7as)-2,7-dihydroxy-2-oxidotetrahydro-4h-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]-1,9-dihydro-6h-purin-6-one
158963B3-56F4-4A85-A160-A80E1460FB19
guanosine-3',5'-cyclic-monophosphate
CHEMBL395336 ,
unii-h2d2x058mu
einecs 231-641-6
h2d2x058mu ,
guanosine cyclic 3',5'-(hydrogen phosphate)
bdbm50369127
EPITOPE ID:149170
9-[(4ar,6r,7r,7as)-2,7-dihydroxy-2-oxo-hexahydro-1,3,5,2$l^{5}-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]-2-amino-6,9-dihydro-1h-purin-6-one
bdbm14391
guanosine-3 ,5 -monophosphate
SCHEMBL738
cyclic gmp [mi]
c-gmp
9-[(4ar,6r,7r,7as)-2,7-dihydroxy-2-oxo-hexahydro-2??-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]-2-amino-6,9-dihydro-1h-purin-6-one
AKOS016845882
ZOOGRGPOEVQQDX-UUOKFMHZSA-N
DTXSID8040646
9-[(4ar,6r,7r,7as)-2,7-dihydroxy-2-oxo-hexahydro-1,3,5,2$l^{5}-furo[3,2-d][1,3,2$l^{5}]dioxaphosphinin-6-yl]-2-amino-6,9-dihydro-1h-purin-6-one
AS-60024
3',5'-guanosine
2-amino-9-[(2s,4ar,6r,7r,7as)-2,7-dihydroxy-2-oxidotetrahydro-4h-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]-1,9-dihydro-6h-purin-6-one
SCHEMBL19222127
Q422511
2-amino-9-((4ar,6r,7r,7as)-2,7-dihydroxy-2-oxidotetrahydro-4h-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl)-1,9-dihydro-6h-purin-6-one
guanosine-3',5'-cyclic monophosphate
mfcd00070129
3',5'-cgmp
9-[(4ar,6r,7r,7as)-2,7-dihydroxy-2-oxo-4a,6,7,7a-tetrahydro-4h-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]-2-amino-1h-purin-6-one

Toxicity

ExcerptReference
" Our data provide evidence that NO, synthesized upon glutamate exposure, has not a primary toxic action in pure hippocampal neuronal cultures."( Blockade of nitric oxide formation does not prevent glutamate-induced neurotoxicity in neuronal cultures from rat hippocampus.
Leysen, JE; Pauwels, PJ, 1992
)
"-) immunoreactivity is colocalized with nicotinamide adenine di-nucleotide phosphate diaphorase in neurons that are uniquely resistant to toxic insults."( Nitric oxide mediates glutamate neurotoxicity in primary cortical cultures.
Bredt, DS; Dawson, TM; Dawson, VL; London, ED; Snyder, SH, 1991
)
" These findings argue strongly for a direct toxic effect of ethanol, and are furthermore compatible with behavioural changes in chronic alcoholics, dominated by memory impairment."( The neurotoxicity of ethanol.
Melgaard, B, 1983
)
"Inclusion of sodium nitroprusside (Na2[Fe(2+)-(CN)5NO]) into the culture medium is toxic to cultured rat cerebellar granule neurons."( Inhibition of excitatory amino acid-induced phosphoinositide hydrolysis as a possible mechanism of nitroprusside neurotoxicity.
Chuang, DM; Yu, O, 1996
)
" The neuropeptide vasoactive intestinal peptide and inhibitors of poly(ADP-ribose) polymerase also prevented this injury, but without inhibiting NO synthesis, both acting by inhibiting a toxic action of NO that is critical to tissue injury."( Excitotoxicity in the lung: N-methyl-D-aspartate-induced, nitric oxide-dependent, pulmonary edema is attenuated by vasoactive intestinal peptide and by inhibitors of poly(ADP-ribose) polymerase.
Berisha, HI; Pakbaz, H; Said, SI, 1996
)
" These results imply that cGMP and NO do not modulate the toxic effects of Glu and are therefore unsuitable as biomarkers of excitotoxicity in these cells."( Glutamate toxicity in primary cerebellar cultures from mouse brain is unaffected by changes in cGMP levels.
Grieve, A; Griffiths, R; Malcolm, CS; Ritchie, L, 1996
)
"Extracellular levels of endogenous glutamate are relatively high in the developing rabbit retina but nonetheless appear to promote cell survival and developmental processes at concentrations considered toxic in the adult."( N-methyl-D-aspartate-mediated glutamate toxicity in the developing rabbit retina.
Haberecht, MF; Lo, GJ; Mitchell, CK; Redburn, DA, 1997
)
"The results presented in this study indicate that the toxic response brought about by increasing concentrations of tert-butylhydroperoxide in CHP100 cells was mitigated significantly by exogenously added nitric oxide donors via a cyclic GMP-independent mechanism."( Different signalling pathways mediate the opposite effects of endogenous versus exogenous nitric oxide on hydroperoxide toxicity in CHP100 neuroblastoma cells.
Cantoni, O; Clementi, E; Guidarelli, A; Sciorati, C, 1999
)
" Furthermore, while the toxic effect of NOR3 was attenuated by replacing the medium at 20 min, 1 or 2 h after drug addition, it was continued by replacing the medium at 3 h or later after drug addition."( Kinetic characterization of the nitric oxide toxicity for PC12 cells: effect of half-life time of NO release.
Kato, T; Nakamura, K; Yamamoto, H; Yamamoto, T; Yuyama, K, 2000
)
" Treatment-related adverse events were experienced by 43% of the patients administered GW660511X 200 mg and 44% of those dosed with placebo with headache the most commonly reported."( A randomized, double-blind, placebo-controlled, parallel-group study to assess the efficacy and safety of dual ACE/NEP inhibitor GW660511X in mild-to-moderate hypertensive patients.
Danoff, TM; Johnson, AG; Pearce, GL, 2006
)
" No serious adverse events were reported; there were no life-threatening events."( Single-dose pharmacokinetics, pharmacodynamics, tolerability, and safety of the soluble guanylate cyclase stimulator BAY 63-2521: an ascending-dose study in healthy male volunteers.
Artmeier-Brandt, U; Frey, R; Mück, W; Unger, S; Weimann, G; Wensing, G, 2008
)
" No serious adverse events were reported."( Pharmacokinetics, pharmacodynamics, tolerability, and safety of the soluble guanylate cyclase activator cinaciguat (BAY 58-2667) in healthy male volunteers.
Artmeier-Brandt, U; Frey, R; Mück, W; Unger, S; Weimann, G; Wensing, G, 2008
)
" The primary outcome measure was the adverse occurrence of any of the following during the treatment period: stroke worsening, new stroke, myocardial infarction, vision loss, hearing loss, or death from any cause."( Sildenafil treatment of subacute ischemic stroke: a safety study at 25-mg daily for 2 weeks.
Chopp, M; Katramados, A; Lewandowski, CA; Lu, M; McCarthy, S; Mitsias, P; Morris, DC; Russman, AN; Silver, B,
)
"Sildenafil (25 mg daily for 2 weeks) appeared to be safe in this group of patients with mild to moderately severe stroke."( Sildenafil treatment of subacute ischemic stroke: a safety study at 25-mg daily for 2 weeks.
Chopp, M; Katramados, A; Lewandowski, CA; Lu, M; McCarthy, S; Mitsias, P; Morris, DC; Russman, AN; Silver, B,
)
" Randomised, controlled trials demonstrate that these therapies can be associated with sexual adverse effects (AEs) such as loss of libido, erectile dysfunction and ejaculatory disorders."( Current benign prostatic hyperplasia treatment: impact on sexual function and management of related sexual adverse events.
Berges, R; Giuliano, F; Kirby, M; Mirone, V; Moncada, I; Sessa, A, 2011
)
" The cytotoxic IC(50) of all synthesized compounds was approximately twofold greater than their required concentration for inhibition of PDE-4 (in terms of elevation of cAMP), and thus, these structures could be used to develop potent and safe inhibitors of PDE-4 enzyme."( Safety and efficacy of new 3,6-diaryl-7H-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazine analogs as potential phosphodiesterase-4 inhibitors in NIH-3T3 mouse fibroblastic cells.
Abdollahi, M; Baeeri, M; Firoozpour, L; Foroumadi, A; Motamedi, M; Ostad, SN; Shafiee, A; Souzangarzadeh, S; Yahya-Meymandi, A, 2011
)
" Nitrite thus appears safe and effective for clinical translation as a promising therapy against cardiac arrest mediated heart and brain injury."( Nitrite therapy is neuroprotective and safe in cardiac arrest survivors.
Alekseyenko, A; Dave, KR; Dezfulian, C; Do, R; Kim, F; Perez-Pinzon, MA; Raval, AP, 2012
)
" OLG treatment at two different doses (15 or 30 mg/kg body weight) and two different time points (1 day or 7 days of treatment) demonstrated that no toxic effects were observed on heart, liver and renal functions."( Safety of oligonol, a highly bioavailable lychee-derived polyphenolic antioxidant, on liver, kidney and heart function in rats.
Bagchi, M; Fujii, H; Moriyama, H; Thirunavukkarasu, M; Wakame, K; Zhan, L, 2012
)
" Therefore, simultaneous administration of iNO during perinatal hypoxic exposure seems able to prevent adverse effects of perinatal hypoxia on the adult pulmonary circulation."( Perinatal nitric oxide therapy prevents adverse effects of perinatal hypoxia on the adult pulmonary circulation.
Delhaes, F; Diaceri, G; Menétrey, S; Peyter, AC; Tolsa, JF, 2014
)
" Whereas wild-type cells tolerated a sudden exposure to a toxic concentration of toluene, a tolR mutant strain or a strain overexpressing a diguanylate cyclase gene lost viability upon toluene shock."( Degradation of cyclic diguanosine monophosphate by a hybrid two-component protein protects Azoarcus sp. strain CIB from toluene toxicity.
Baraquet, C; Blázquez, B; Díaz, E; Harwood, CS; Martín-Moldes, Z; Zamarro, MT, 2016
)
" No serious or severe adverse events (AEs) were reported."( A Randomized, Placebo-Controlled, Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Soluble Guanylate Cyclase Stimulator Praliciguat in Healthy Subjects.
Chickering, JG; Currie, MG; Hall, M; Hanrahan, JP; Mihova, M; Milne, GT; Profy, AT; Ruff, D; Wakefield, JD; Wilson, PJ, 2019
)
" Despite its positive effect on PCa patient survival, ADT causes various adverse effects, including increased cardiovascular risk factors and cardiotoxicity."( Cardiovascular risks and toxicity - The Achilles heel of androgen deprivation therapy in prostate cancer patients.
Batra, SK; Das, A; Datta, K; Kukreja, RC; Muniyan, S; Teply, BA; Xi, L, 2020
)
" There were no deaths or serious adverse events."( Safety, pharmacodynamic, and pharmacokinetic characterization of vericiguat: results from six phase I studies in healthy subjects.
Arens, E; Becker, C; Boettcher, M; Loewen, S; Mueck, W; Thomas, D; Yoshikawa, K, 2021
)

Pharmacokinetics

ExcerptReference
" The rates of relaxation were then used to construct a pharmacodynamic model that described the time course of relaxation for these compounds."( Pharmacodynamic modeling of the in vitro vasodilating effects of organic mononitrates.
Fung, HL; Tzeng, TB, 1992
)
" Synthetic ANF increased plasma ANF concentration by similar amounts, but the elimination half-life (t 1/2) for synthetic ANF was longer in the heart failure group (6."( Atrial natriuretic factor: pharmacokinetics and cyclic GMP response in relation to biologic effects in severe heart failure.
Armstrong, PW; Canepa-Anson, R; Moe, GW, 1992
)
" The plasma half-life of CNP on termination of infusion was rapid (1."( Biological actions and pharmacokinetics of C-type natriuretic peptide in conscious sheep.
Charles, CJ; Espiner, EA; Nicholls, MG; Richards, AM; Yandle, TG, 1995
)
" Clearance was 544+/-24 (440-620), 894+/-164 (470-1190), and 1018+/-230 (710-2130) ml min(-1), and elimination half-life was calculated as 41."( L-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship.
Bode-Böger, SM; Böger, RH; Frölich, JC; Galland, A; Tsikas, D, 1998
)
" The mechanism by which caffeine increases the antinociceptive action of NSAIDs does not appear to include a pharmacokinetic interaction."( A review of the pharmacokinetic and pharmacodynamic factors in the potentiation of the antinociceptive effect of nonsteroidal anti-inflammatory drugs by caffeine.
Castañeda-Hernández, G; Granados-Soto, V, 1999
)
" The pharmacokinetic data indicate that Z13752A administered orally is rapidly absorbed and available to the systemic circulation in humans."( A double-blind, placebo-controlled study to assess tolerability, pharmacokinetics and preliminary pharmacodynamics of single escalating doses of Z13752A, a novel dual inhibitor of the metalloproteases ACE and NEP, in healthy volunteers.
Bani, M; Colantoni, A; Guillaume, M; Macchi, F; Moroni, G; Persiani, S, 2000
)
" The pharmacokinetic and pharmacodynamic effects of omapatrilat are consistent with once-daily dosing."( Pharmacokinetics and pharmacodynamics of the vasopeptidase inhibitor, omapatrilat in healthy subjects.
Delaney, C; Ferreira, I; Ford, N; Jemal, M; Liao, WC; Swanson, B; Uderman, H; Vesterqvist, O, 2003
)
" The clinical efficacy and safety profiles of these medications are related to their molecular mode of action, the selectivity for PDE-5, and the pharmacokinetic properties (absorption, bioavailability, time to onset of action, distribution, metabolism, and elimination)."( Molecular mechanisms and pharmacokinetics of phosphodiesterase-5 antagonists.
Corbin, JD; Francis, SH, 2003
)
"Our objective was to define the pharmacodynamic profile of the new dual neutral endopeptidase (NEP)/angiotensin-converting enzyme (ACE) inhibitor AVE7688."( Pharmacokinetics and pharmacodynamics of the vasopeptidase inhibitor AVE7688 in humans.
Azizi, M; Bissery, A; Floch, A; Guyene, TT; Ménard, J; Ozoux, ML; Peyrard, S, 2006
)
"AVE7688 at a dose of 25 mg has a favorable pharmacodynamic profile compared with other RAS blockers."( Pharmacokinetics and pharmacodynamics of the vasopeptidase inhibitor AVE7688 in humans.
Azizi, M; Bissery, A; Floch, A; Guyene, TT; Ménard, J; Ozoux, ML; Peyrard, S, 2006
)
" The pharmacodynamic and pharmacokinetic properties of BAY 63-2521 suggest that it can offer a unique mode of action in the treatment of pulmonary hypertension."( Single-dose pharmacokinetics, pharmacodynamics, tolerability, and safety of the soluble guanylate cyclase stimulator BAY 63-2521: an ascending-dose study in healthy male volunteers.
Artmeier-Brandt, U; Frey, R; Mück, W; Unger, S; Weimann, G; Wensing, G, 2008
)
" An exploratory analysis of pharmacodynamic parameters was also conducted."( Pharmacokinetics of the soluble guanylate cyclase activator cinaciguat in individuals with hepatic impairment.
Blunck, M; Frey, R; Gnoth, MJ; Mück, W; Scheerans, C; Schmidt, A; Unger, S; Wensing, G, 2012
)
" Pharmacokinetic properties of sildenafil in rodents were investigated using (11) C-radiolabeling followed by in vivo positron emission tomography (PET) and ex vivo tissue dissection and gamma counting."( Pharmacokinetic investigation of sildenafil using positron emission tomography and determination of its effect on cerebrospinal fluid cGMP levels.
Cuadrado-Tejedor, M; Dopeso-Reyes, IG; Franco, R; García-Barroso, C; García-Osta, A; Gómez-Vallejo, V; Lanciego, JL; Llop, J; Oyarzabal, J; Szczupak, B; Ugarte, A, 2016
)
" Given the potential for co-administration of both drugs in patients with heart failure, this study was designed to investigate the potential for a pharmacodynamic drug interaction affecting blood pressure."( Pharmacodynamic interaction between intravenous nitroglycerin and oral sacubitril/valsartan (LCZ696) in healthy subjects.
Ayalasomayajula, S; Buchbjerg, J; Golor, G; Hinder, M; Langenickel, TH; Pal, P; Prescott, MF; Schuehly, U; Sunkara, G, 2018
)
"The results from this study demonstrate no pharmacodynamic drug interaction between nitroglycerin and sacubitril/valsartan in healthy subjects, suggesting that no change of dose selection and escalation recommendations or clinical monitoring during nitroglycerin administration is required."( Pharmacodynamic interaction between intravenous nitroglycerin and oral sacubitril/valsartan (LCZ696) in healthy subjects.
Ayalasomayajula, S; Buchbjerg, J; Golor, G; Hinder, M; Langenickel, TH; Pal, P; Prescott, MF; Schuehly, U; Sunkara, G, 2018
)
" Pharmacokinetics were dose proportional, with an effective half-life of 24-37 hours, supporting once-daily dosing."( A Randomized, Placebo-Controlled, Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Soluble Guanylate Cyclase Stimulator Praliciguat in Healthy Subjects.
Chickering, JG; Currie, MG; Hall, M; Hanrahan, JP; Mihova, M; Milne, GT; Profy, AT; Ruff, D; Wakefield, JD; Wilson, PJ, 2019
)
" Pharmacodynamic study was performed via biochemical analysis of cyclic guanosine monophosphate (cGMP) in rat penis 2-h post-treatment and compared with oral suspension of Cialis® tablets."( Intranasal Tadalafil nanoemulsions: formulation, characterization and pharmacodynamic evaluation.
Abdelmonsif, DA; Boraie, N; Elbardisy, B; Galal, S, 2019
)
"5 h [fasted]) with a mean half-life of about 22."( Safety, pharmacodynamic, and pharmacokinetic characterization of vericiguat: results from six phase I studies in healthy subjects.
Arens, E; Becker, C; Boettcher, M; Loewen, S; Mueck, W; Thomas, D; Yoshikawa, K, 2021
)
"This study shows that pentoxifylline has minimal temperature-dependent pharmacodynamic changes, and that it can inhibit elimination of both cAMP and cGMP at low temperatures."( Pharmacodynamic properties for inhibition of cAMP- and cGMP elimination by pentoxifylline remain unaltered in vitro during hypothermia.
Dietrichs, ES; Fuskevåg, OM; Kondratiev, T; Kuzmiszyn, AK; Sager, G; Selli, AL; Smaglyukova, N, 2022
)

Compound-Compound Interactions

ExcerptReference
"Molsidomine and its vasoactive metabolite SIN-1 elicit anti-ischemic properties by a therapeutically useful pattern of different vasoactive actions combined with a cyclic GMP-mediated inhibition of platelet adhesion and aggregation."( Anti-ischemic actions of molsidomine by venous and large coronary dilatation in combination with antiplatelet effects.
Bassenge, E; Mülsch, A, 1989
)
" The pulmonary vasodilation obtained with NO alone could be prolonged from 12 to 42 min when inhaled NO was combined with IV dipyridamole, accounting for a time-weighted reduction in NO exposure by 72%."( Intermittent nitric oxide combined with intravenous dipyridamole in a piglet model of acute pulmonary hypertension.
De Somer, F; De Wolf, D; Foubert, L; Mortier, E; Reyntjens, K; Van Belleghem, Y; Van Nooten, G, 2003
)
" Intermittent NO inhalation combined with IV dipyridamole decreases pulmonary artery pressure for a prolonged period of time and reduces exposure to NO."( Intermittent nitric oxide combined with intravenous dipyridamole in a piglet model of acute pulmonary hypertension.
De Somer, F; De Wolf, D; Foubert, L; Mortier, E; Reyntjens, K; Van Belleghem, Y; Van Nooten, G, 2003
)
" However, when combined with cAMP elevation substantial regeneration of adult neurites is achieved, superior to that achieved with either cAMP or cGMP alone."( cGMP promotes neurite outgrowth and growth cone turning and improves axon regeneration on spinal cord tissue in combination with cAMP.
Murray, AJ; Peace, AG; Shewan, DA, 2009
)
" These results indicate that procyanidin-induced vasorelaxation is associated with NO-cGMP pathway in combination with hyperpolarization due to multiple activation of Ca(2+)-dependent and -independent K(+) channels."( Apple procyanidins induced vascular relaxation in isolated rat aorta through NO/cGMP pathway in combination with hyperpolarization by multiple K+ channel activations.
Byun, EB; Kanda, T; Korematsu, S; Matsui, T; Nishizuka, T; Ohshima, S, 2009
)
" In this study, a murine model was used to compare sublingual administration with intranasal and intramuscular administration of influenza H5N1 virosomes (2 µg haemagglutinin; HA) in combination with the mucosal adjuvant (3',5')-cyclic dimeric guanylic acid (c-di-GMP)."( Evaluation of the sublingual route for administration of influenza H5N1 virosomes in combination with the bacterial second messenger c-di-GMP.
Bredholt, G; Cox, RJ; Ebensen, T; Gjeraker, IH; Guzmán, CA; Pedersen, GK; Svindland, S, 2011
)
"We investigated if soluble guanylate cyclase stimulation either alone or in combination with phosphodiesterase-5 (PDE5) inhibition could prevent pressure overload-induced right ventricular (RV) hypertrophy and failure."( The effects of cyclic guanylate cyclase stimulation on right ventricular hypertrophy and failure alone and in combination with phosphodiesterase-5 inhibition.
Andersen, A; Holmboe, S; Nielsen, JM; Nielsen-Kudsk, JE; Vildbrad, MD, 2013
)
"Stimulation of soluble guanylate cyclase by BAY 41-2272 alone or in combination with sildenafil failed to prevent the development of RV hypertrophy and failure in rats subjected to pulmonary trunk banding."( The effects of cyclic guanylate cyclase stimulation on right ventricular hypertrophy and failure alone and in combination with phosphodiesterase-5 inhibition.
Andersen, A; Holmboe, S; Nielsen, JM; Nielsen-Kudsk, JE; Vildbrad, MD, 2013
)
"To assess the urodynamic effects of soluble guanylyl cyclase (sGC) stimulator, BAY 41-2272, and activator, BAY 60-2770, (which both are able to induce cGMP synthesis even in the absence of nitric oxide (NO)) alone or in combination with a phosphodiesterase type 5 (PDE5) inhibitor, vardenafil, in a model of partial urethral obstruction (PUO) induced bladder overactivity (BO)."( Reduction of obstruction related bladder overactivity by the guanylyl cyclase modulators BAY 41-2272 and BAY 60-2770 alone or in combination with a phosphodiesterase type 5 inhibitor.
Andersson, KE; Bauer, RM; Füllhase, C; Gratzke, C; Hennenberg, M; Niedworok, C; Sandner, P; Soler, R; Stief, C; Strittmatter, F, 2015
)

Bioavailability

ExcerptReference
" Pharmacokinetic and biotransformation studies indicate that prazosin is well absorbed and is excreted principally in metabolized form with biliary excretion being the major route of elimination."( Prazosin: biochemistry and structure-activity studies.
Hess, HJ, 1975
)
") also decreased basal cGMP levels in mouse cerebellum for up to 3 h, a result suggesting brain bioavailability and a long duration of NMDA receptor antagonism in vivo."( Neurochemical interactions of competitive N-methyl-D-aspartate antagonists with dopaminergic neurotransmission and the cerebellar cyclic GMP system: functional evidence for a phasic glutamatergic control of the nigrostriatal dopaminergic pathway.
Cler, JA; Contreras, PC; Emmett, MR; Farah, JM; Iyengar, S; Mick, SJ; Rao, TS; Wood, PL, 1991
)
") injections of HA-966, demonstrating the bioavailability of this glycine receptor antagonist."( In vivo antagonism of agonist actions at N-methyl-D-aspartate and N-methyl-D-aspartate-associated glycine receptors in mouse cerebellum: studies of 1-hydroxy-3-aminopyrrolidone-2.
Cler, J; Emmett, MR; Iyengar, S; Mick, S; Oei, E; Rao, TS; Wood, PL, 1990
)
"01) in neutrophils incubated with both sodium nitroprusside (SNP), an exogenous source of nitric oxide, and N-acetylcysteine (NAC), which increases the bioavailability of nitric oxide; this increase indicates that neutrophils contain a nitric oxide-sensitive guanylate cyclase."( Nitric oxide regulates endotoxin-induced TNF-alpha production by human neutrophils.
Cobb, JP; Corriveau, CC; Danner, RL; Madara, PJ; Tropea, MM; Van Dervort, AL; Wesley, RA; Yan, L, 1994
)
") did not affect cGMP responses, suggesting poor bioavailability in brain."( Indole-2-carboxylates, novel antagonists of the N-methyl-D-aspartate (NMDA)-associated glycine recognition sites: in vivo characterization.
Cler, JA; Cordi, AA; Dappen, MS; Emmett, MR; Gray, NM; Iyengar, S; Mick, SJ; Monahan, JB; Rao, TS; Wood, PL, 1993
)
" ratio for SR 27897 was near unity, suggesting a high oral bioavailability of the compound."( Neurobehavioural effects of SR 27897, a selective cholecystokinin type A (CCK-A) receptor antagonist.
Arnone, M; Gonalons, N; Gueudet, C; Gully, D; Heaulme, M; Keane, P; Le Fur, G; Poncelet, M; Santucci, V; Thurneyssen, O, 1993
)
" These data show that, in these patients' plasmas, impaired metabolism of reactive oxygen species reduces the bioavailability of NO and impairs normal platelet inhibitory mechanisms."( Decreased platelet inhibition by nitric oxide in two brothers with a history of arterial thrombosis.
Barnard, MR; Benoit, SE; Freedman, JE; Loscalzo, J; Michelson, AD; Valeri, CR, 1996
)
" This may represent a therapeutic strategy for vascular diseases characterized by decreased bioavailability of NO."( Adventitial gene transfer of recombinant endothelial nitric oxide synthase to rabbit carotid arteries alters vascular reactivity.
Barber, DA; Crotty, TB; Gloviczki, P; Katusic, ZS; Kullo, IJ; Mozes, G; O'Brien, T; Schwartz, RS, 1997
)
" The effective lymphatic absorption rate was not different."( Icodextrin with nitroprusside increases ultrafiltration and peritoneal transport during long CAPD dwells.
de Waart, DR; Douma, CE; Hiralall, JK; Krediet, RT; Struijk, DG, 1998
)
" Split-drop micropuncture was performed on anesthetized rats to determine the effects of ANF and the NO donor sodium nitroprusside (SNP) on proximal tubular fluid absorption rate (Jva)."( Inhibition of proximal tubular fluid absorption by nitric oxide and atrial natriuretic peptide in rat kidney.
Eitle, E; Harris, PJ; Hiranyachattada, S; Wang, H, 1998
)
" Oral bioavailability of L-arginine was 68+/-9 (51-87)%."( L-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship.
Bode-Böger, SM; Böger, RH; Frölich, JC; Galland, A; Tsikas, D, 1998
)
" These results suggest that reduced NO bioavailability observed in cholesterol-induced vascular dysfunction can be partially overcome by eNOS gene transfer."( Ex vivo gene transfer of endothelial nitric oxide synthase to atherosclerotic rabbit aortic rings improves relaxations to acetylcholine.
Cable, DG; Crotty, TB; Gloviczki, P; Katusic, ZS; Kullo, IJ; Mohacsi, TG; Mozes, G; O'Brien, T; Spector, DJ, 1998
)
" Pharmacokinetic analysis of several compounds indicated excellent oral bioavailability and a reasonable half-life in rats."( Piperazine imidazo[1,5-a]quinoxaline ureas as high-affinity GABAA ligands of dual functionality.
Belonga, KL; Carter, DB; Im, HK; Im, WB; Jacobsen, EJ; Mickelson, JW; Petke, JD; Sethy, VH; Stelzer, LS; Tang, AH; TenBrink, RE; VonVoigtlander, PF; Zhong, WZ, 1999
)
" This mechanism of vasodilatation may have beneficial effects in the prevention and treatment of vascular disorders characterized by the diminished bioavailability of NO, such as cerebral vasospasm."( Adventitia-dependent relaxations of canine basilar arteries transduced with recombinant eNOS gene.
Iida, Y; Katusic, ZS; O'Brien, T; Onoue, H; Smith, L; Tsutsui, M, 1999
)
"Endothelial dysfunction, as observed in hypertension and atherosclerosis, is associated with a reduction in the bioavailability of endothelium-derived nitric oxide (NO)."( Downregulation of soluble guanylyl cyclase in young and aging spontaneously hypertensive rats.
Linz, W; Ruetten, H; Schmidt, HH; Zabel, U, 1999
)
"Reduced local bioavailability and adverse side effects limit systemic administration of NO to modulate vascular response to injury."( Polymeric-based perivascular delivery of a nitric oxide donor inhibits intimal thickening after balloon denudation arterial injury: role of nuclear factor-kappaB.
Cercek, B; Dimayuga, P; Fishbein, MC; Kaul, S; Molloy, MD; Nilsson, J; Parikh, AK; Rajavashisth, TB; Rengstrom, J; Shah, PK; Xu, XP, 2000
)
" Therefore, we investigated whether endothelial dysfunction and/or vascular NO bioavailability is reflected by decreased vessel wall P-VASP and whether improvement of endothelial dysfunction restores this P-VASP."( Vasodilator-stimulated phosphoprotein serine 239 phosphorylation as a sensitive monitor of defective nitric oxide/cGMP signaling and endothelial dysfunction.
Bodenschatz, M; Hoffmann, N; Meinertz, T; Mollnau, H; Münzel, T; Oelze, M; Skatchkov, M; Smolenski, A; Walter, U; Warnholtz, A, 2000
)
" In conclusion, experimental HC attenuates in vitro endothelium-dependent relaxation of the porcine renal artery, possibly due to low bioavailability of NO."( Impaired renal vascular endothelial function in vitro in experimental hypercholesterolemia.
Caccitolo, JA; Lerman, A; Lerman, LO; Rodriguez Porcel, M; Romero, JC; Schaff, HV; Stulak, JM; Wilson, SH, 2001
)
"05), mimicking the effect of an apparent decrease in bioavailability of endogenous NO."( Chronic nicotine alters NO signaling of Ca(2+) channels in cerebral arterioles.
Gerzanich, V; Simard, JM; West, GA; Zhang, F, 2001
)
" Compound 12 also shows 22% oral bioavailability in rats."( Solution-Phase parallel synthesis of 5-carboxamido 1-benzyl-3-(3-dimethylaminopropyloxy)-1H-pyrazoles as activators of soluble guanylate cyclase with improved oral bioavailability.
Brummell, DG; Glen, RC; Goggin, MC; Reynolds, K; Selwood, DL; Tatlock, MA; Wishart, G, 2001
)
" We previously identified increased vascular superoxide formation and reduced NO bioavailability as one causal mechanism."( Effects of in vivo nitroglycerin treatment on activity and expression of the guanylyl cyclase and cGMP-dependent protein kinase and their downstream target vasodilator-stimulated phosphoprotein in aorta.
Hink, U; Klöss, S; Meinertz, T; Mollnau, H; Mülsch, A; Münzel, T; Oelze, M; Smolenski, A; Stasch, JP; Töpfer, A; Walter, U; Warnholtz, A, 2001
)
"N-acetyl-L-cysteine exerts direct anti-aggregating effects through an increased bioavailability of platelet nitric oxide."( N-acetyl-L-cysteine exerts direct anti-aggregating effect on human platelets.
Anfossi, G; Cavalot, F; Massucco, P; Mattiello, L; Russo, I; Trovati, M, 2001
)
" bioavailability may represent a common factor responsible for the vascular and glomerular dysfunction."( Oxidative stress and renal dysfunction in salt-sensitive hypertension.
Loscalzo, J; Rudd, MA; Trolliet, MR, 2001
)
" High glucose inhibits nitric oxide (NO) bioavailability and decreased NO increases TGF-beta activity and extracellular matrix accumulation."( Nitric oxide and cGMP-dependent protein kinase regulation of glucose-mediated thrombospondin 1-dependent transforming growth factor-beta activation in mesangial cells.
Darley-Usmar, V; Murphy-Ullrich, JE; Poczatek, MH; Shiva, S; Wang, S, 2002
)
"-) generation, thus the bioavailability of (*)NO was increased."( A flavonoid-rich diet increases nitric oxide production in rat aorta.
Benito, S; Buxaderas, S; Lopez, D; Mitjavila, MT; Puig-Parellada, P; Sáiz, MP; Sánchez, J, 2002
)
" Monocrotaline-induced pulmonary hypertension is associated with low bioavailability of nitric oxide."( Effects of monocrotaline on endothelial nitric oxide synthase expression and sulfhydryl levels in rat lungs.
Gewitz, MH; Kumar, A; Mathew, R; Rosenfeld, L; Yuan, N,
)
" Altered superoxide production and NO bioavailability have been implicated in contributing to the development of tolerance, an effect that may be ameliorated by the administration of antioxidants."( Platelet nitric oxide and superoxide release during the development of nitrate tolerance: effect of supplemental ascorbate.
Devine, AB; Dixon, LJ; Hamilton, P; Hanratty, CG; Leahey, WJ; McGrath, LT; McVeigh, GE; Morgan, DG; Wilson, M, 2002
)
"These data show that the bioavailability of nitric oxide is reduced in aortae from diabetic rabbits due to excess production of superoxide, an effect augmented by homocysteine."( Homocysteine enhances impairment of endothelium-dependent relaxation and guanosine cyclic monophosphate formation in aortae from diabetic rabbits.
Angelini, GD; Jeremy, JY; Mikhailidis, DP; Shukla, N; Thompson, CS, 2002
)
"Reduced endothelium-dependent vasorelaxation partly due to loss of nitric oxide (NO) bioavailability occurs in most cases of chronic hypertension."( Altered vascular function in fetal programming of hypertension.
Beauchamp, M; Bernier, S; Chemtob, S; Gobeil, F; Hou, X; Lahaie, I; Lamireau, D; Nuyt, AM; Varma, DR, 2002
)
" NaCl is poorly absorbed in the CF duct because CFTR activity appears to impose a loss of ENaC activity as well."( Functional interaction of CFTR and ENaC in sweat glands.
Quinton, PM; Reddy, MM, 2003
)
" Impaired endothelium-dependent vasodilation in patients with heart failure can be attributed to decreased bioavailability of nitric oxide and attenuated responses to nitric oxide in vascular smooth muscle."( Potential role of type 5 phosphodiesterase inhibition in the treatment of congestive heart failure.
Katz, SD,
)
" This suggests a reduced NO bioavailability to produce vasodilation and an enhanced sensitivity to NO inhibition."( Hyperhomocysteinemia induces renal hemodynamic dysfunction: is nitric oxide involved?
Cuniberti, LA; Dominguez, GN; Fischer, PA; Martinez, V; Masnatta, LD; Ramirez, AJ; Werba, JP, 2003
)
" This effect seems to be mediated by preservation of NO bioavailability in endothelial cells."( Protective effect of chronic vitamin C treatment on endothelial function of apolipoprotein E-deficient mouse carotid artery.
Akiyama, M; D'uscio, LV; Eguchi, D; Katusic, ZS; Matsumoto, T; Smith, LA, 2003
)
" Potential mechanisms underlying impaired endothelial function and decreased bioavailability of nitric oxide under these clinical conditions are discussed."( Potential mechanisms of impaired endothelial function in arterial hypertension and hypercholesterolemia.
John, S; Schmieder, RE, 2003
)
" These results suggest that prolonged exposure of rabbits to oral arsenate may impair the bioavailability of BH(4) in endothelial cells and, as a consequence, disrupt the balance between NO and O2(."( A potential mechanism for the impairment of nitric oxide formation caused by prolonged oral exposure to arsenate in rabbits.
Hayashi, T; Horiguchi, S; Itoh, K; Kumagai, Y; Nikaido, M; Pi, J; Shimojo, N; Sun, G; Sun, Y; Waalkes, MP; Yamamoto, M; Yamauchi, H, 2003
)
" We tested the hypotheses that arginase reciprocally regulates NOS by modulating L-arginine bioavailability and that arginase is upregulated in aging vasculature, contributing to depressed endothelial function."( Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels.
Berkowitz, DE; Burke, S; Cernetich, A; Champion, HC; Hare, JM; Kim, S; Li, D; Minhas, KM; Nyhan, D; Shoukas, AA; White, R, 2003
)
" The close proximity of red blood cells suggests, however, that a significant amount of NO released will be scavenged by blood, and thus the issue of bioavailability of endothelium-derived NO to smooth muscle has been investigated experimentally and theoretically."( A theoretical model of nitric oxide transport in arterioles: frequency- vs. amplitude-dependent control of cGMP formation.
Kavdia, M; Popel, AS; Tsoukias, NM, 2004
)
"We hypothesized that neuronal NO release as well as its bioavailability and vasomotor response could be affected when aging and hypertension are present simultaneously."( Aging increases neuronal nitric oxide release and superoxide anion generation in mesenteric arteries from spontaneously hypertensive rats.
Balfagón, G; Ferrer, M; Minoves, N; Salaices, M; Sánchez, M,
)
" The bioavailability of vascular."( Upregulation of endothelial nitric oxide synthase in rat aorta after ingestion of fish oil-rich diet.
Casós, K; Farriol, M; López, D; Mitjavila, MT; Orta, X; Puig-Parellada, P; Sáiz, MP, 2004
)
"These results indicate that tissue kallikrein protects against renal fibrosis in hypertensive DSS rats through increased nitric oxide bioavailability and suppression of oxidative stress and TGF-beta expression."( Tissue kallikrein attenuates salt-induced renal fibrosis by inhibition of oxidative stress.
Bledsoe, G; Chao, J; Chao, L; Kato, K; Zhang, JJ, 2004
)
" A reduction of NO bioavailability leads to endothelial dysfunction that has been shown to be improved by alpha-tocopherol in certain conditions."( Alpha-Tocopherol and endothelial nitric oxide synthesis.
Heller, R; Werner, ER; Werner-Felmayer, G, 2004
)
" Unfortunately, the low aqueous solubility and poor oral bioavailability rendered them undesirable development candidates."( Pyrroloquinolone PDE5 inhibitors with improved pharmaceutical profiles for clinical studies on erectile dysfunction.
Bhattacharjee, S; Guan, J; Haynes-Johnson, D; Jiang, W; John, TM; Kraft, P; Lundeen, S; Macielag, MJ; Qiu, Y; Sui, Z; Zhang, S, 2005
)
"Acute respiratory distress syndrome (ARDS) is associated with increased superoxide (O(2)(*-)) formation in the pulmonary vasculature and negation of the bioavailability of nitric oxide (NO)."( Sildenafil citrate and sildenafil nitrate (NCX 911) are potent inhibitors of superoxide formation and gp91phox expression in porcine pulmonary artery endothelial cells.
Angelini, GD; Jeremy, JY; Muzaffar, S; Shukla, N; Srivastava, A, 2005
)
" Detection of cGMP was used as a reporter assay for the bioavailability of NO."( Azithromycin reduces Chlamydia pneumoniae-induced attenuation of eNOS and cGMP production by endothelial cells.
Bevers, LM; Bouter, KP; Bouwman, JJ; Diepersloot, RJ; van der Vlist, WE; Visseren, FL, 2005
)
" It has been demonstrated, however, that copper augments the inhibitory effect of homocysteine on nitric oxide (NO)-mediated relaxation of the rat aorta through increased superoxide formation, which reacts with NO thereby reducing the bioavailability of NO."( Penicillamine administration reverses the inhibitory effect of hyperhomocysteinaemia on endothelium-dependent relaxation and superoxide formation in the aorta of the rabbit.
Angelini, GD; Jeremy, JY; Jones, RA; Koupparis, A; Persad, R; Shukla, N, 2006
)
"Reduced nitric oxide (NO) bioavailability and impaired vascular function are the key pathological characteristics of inflammatory diseases such as atherosclerosis."( L-arginine chlorination results in the formation of a nonselective nitric-oxide synthase inhibitor.
Cheng, Y; Jennings, LK; Ji, R; Sun, JZ; Yang, J; Zhang, C, 2006
)
" Dose-response curves of the probucol groups showed an improvement in endothelium-dependent relaxations, associated with increased nitric oxide bioavailability and decreased angiotensin II and hydroperoxide levels."( Role of probucol on endothelial dysfunction of epicardial coronary arteries associated with left ventricular hypertrophy.
Aubin, MC; Carrier, M; Perrault, LP; Shi, YF; Tardif, JC, 2006
)
" These data suggest that dietary RPO may improve myocardial ischaemic tolerance by increasing bioavailability of NO and improving NO-cGMP signaling in the heart."( Proposed mechanisms for red palm oil induced cardioprotection in a model of hyperlipidaemia in the rat.
Bester, D; du Toit, EF; Esterhuyse, JS; Strijdom, H; van Rooyen, J, 2006
)
" These findings suggest that the T-786C polymorphism modulates the effects of atorvastatin on NO bioavailability and oxidative stress."( eNOS gene T-786C polymorphism modulates atorvastatin-induced increase in blood nitrite.
Bem, AF; Metzger, IF; Nagassaki, S; Rocha, JB; Sertório, JT; Tanus-Santos, JE, 2006
)
" Nonetheless, DM may cause uncoupling of nitric oxide synthases (NOSs) with reduction in the bioavailability of nitric oxide (NO), which is critical to maintain oocyte viability and prevent aging."( Activation of the cGMP signaling pathway is essential in delaying oocyte aging in diabetes mellitus.
Abu-Soud, HM; Diamond, MP; Gonik, B; Goud, AP; Goud, PT, 2006
)
" Here we have tested this high NO bioavailability hypothesis in the setting of experimental cerebral malaria (ECM), but find instead that low NO bioavailability contributes to the genesis of ECM."( Low nitric oxide bioavailability contributes to the genesis of experimental cerebral malaria.
Contreras, R; Frangos, JA; Gramaglia, I; Intaglietta, M; Meays, D; Nolan, JP; Sobolewski, P; van der Heyde, HC, 2006
)
" The reduced l-arginine bioavailability to nNOS due to accelerated arginase activity would lead to further impairment of neurogenic NO production, in concert with decreased nNOS protein expression."( Roles of attenuated neuronal nitric-oxide synthase protein expression and accelerated arginase activity in impairing neurogenic relaxation of corpus cavernosum in aged rabbits.
Azuma, H; Kihara, K; Masuda, H; Numao, N; Okada, Y; Sakai, Y, 2007
)
" Basal nitric oxide (NO) bioavailability in the aorta was determined from the contractile response induced by the NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME, 10(-4) mol/L)."( Ferulic acid restores endothelium-dependent vasodilation in aortas of spontaneously hypertensive rats.
Fujii, A; Hase, T; Jokura, H; Saito, I; Suzuki, A; Tokimitsu, I; Yamamoto, M, 2007
)
"Ferulic acid restores endothelial function through enhancing the bioavailability of basal and stimulated NO in SHR aortas."( Ferulic acid restores endothelium-dependent vasodilation in aortas of spontaneously hypertensive rats.
Fujii, A; Hase, T; Jokura, H; Saito, I; Suzuki, A; Tokimitsu, I; Yamamoto, M, 2007
)
" Our results might provide a possible explanation for the in vivo antiplatelet effect of resveratrol despite the poor bioavailability and the weak in vitro activity."( Low concentrations of resveratrol potentiate the antiplatelet effect of prostaglandins.
Wang, WY; Wu, CC; Wu, CI; Wu, YC, 2007
)
" These data demonstrate disruption of NO-cGMP signaling in neonatal rat pups exposed to hyperoxia and show that bioavailability of the substrate l-arginine is implicated in the predisposition of this model to airway hyperreactivity."( Disruption of NO-cGMP signaling by neonatal hyperoxia impairs relaxation of lung parenchyma.
Dreshaj, IA; Haxhiu, MA; Kamath, S; Martin, RJ; Sopi, RB; Zaidi, SI, 2007
)
" Surprisingly, we found doubled NO synthase (NOS) II and III levels, no evidence for attenuated NO bioavailability as evidenced by the nitrosative/oxidative stress marker protein nitro tyrosine, and no changes in the expression and activity of the NO receptor, soluble guanylyl cyclase (sGC)."( Sildenafil in hypoxic pulmonary hypertension potentiates a compensatory up-regulation of NO-cGMP signaling.
Grimminger, F; Kemp-Harper, B; Kirsch, M; Schmidt, HH; Weissmann, N, 2008
)
"Impaired nitric oxide (NO) bioavailability and low levels of circulating endothelial progenitor cells (EPC) are correlated to an increased risk for development of cardiovascular diseases."( Growth hormone treatment improves markers of systemic nitric oxide bioavailability via insulin-like growth factor-I.
Bauersachs, J; Fleissner, F; Jakob, M; Klink, I; Stichtenoth, DO; Thum, T; Tsikas, D, 2007
)
" Before and after GH treatment, we analyzed markers of NO bioavailability and EPC levels."( Growth hormone treatment improves markers of systemic nitric oxide bioavailability via insulin-like growth factor-I.
Bauersachs, J; Fleissner, F; Jakob, M; Klink, I; Stichtenoth, DO; Thum, T; Tsikas, D, 2007
)
"GH treatment induced markers of increased NO bioavailability and enhanced circulating EPC numbers in healthy volunteers."( Growth hormone treatment improves markers of systemic nitric oxide bioavailability via insulin-like growth factor-I.
Bauersachs, J; Fleissner, F; Jakob, M; Klink, I; Stichtenoth, DO; Thum, T; Tsikas, D, 2007
)
")NO bioavailability was reflected in decreased cellular cGMP content, associated with increased superoxide anion radical (O(2)(-."( Hydrogen peroxide promotes endothelial dysfunction by stimulating multiple sources of superoxide anion radical production and decreasing nitric oxide bioavailability.
Ellis, NA; Rayner, BS; Stocker, R; Witting, PK; Wu, BJ, 2007
)
" During this study we investigated the alterations in NO synthesis and bioavailability in a model for dietary modulations of insulin sensitivity."( Nitric oxide bioavailability and not production is first altered during the onset of insulin resistance in sucrose-fed rats.
Blouet, C; Huneau, JF; Mariotti, F; Mathe, V; Tome, D, 2007
)
" The activation of liver pericytes is intrinsic to liver pathogenesis, and leads to endothelial dysfunction, including the low bioavailability of nitric oxide (NO)."( Activated pericyte attenuates endothelial functions: nitric oxide-cGMP rescues activated pericyte-associated endothelial dysfunctions.
Chatterjee, S; Kolluru, GK; Majumder, S; Muley, A; Murty, KV; Nair, CM; Omanakuttan, A; Tamilarasan, KP, 2007
)
" Since nitric oxide bioavailability is decreased in sickle cell disease and nitric oxide may inhibit leukocyte adhesion, we investigated whether stimulation of NO-signaling pathways can reduce the adhesive properties of neutrophils from sickle cell disease individuals (sickle cell diseaseneu)."( Increased adhesive properties of neutrophils in sickle cell disease may be reversed by pharmacological nitric oxide donation.
Canalli, AA; Conran, N; Costa, FF; Franco-Penteado, CF; Saad, ST, 2008
)
" Moreover, diabetes alters the bioavailability of nitric oxide in platelets."( Platelet signalling abnormalities in patients with type 2 diabetes mellitus: a review.
El Haouari, M; Rosado, JA,
)
"Increased formation of reactive oxygen species (ROS) has been identified as a causative factor in endothelial dysfunction by reducing NO bioavailability and uncoupling endothelial nitric oxide synthase (eNOS)."( Paradoxical activation of endothelial nitric oxide synthase by NADPH oxidase.
Banfi, B; Belin de Chantemele, E; Fulton, DJ; Gupta, S; Jagnandan, D; Malik, P; Marrero, MB; Pandey, D; Rudic, RD; Stepp, DW; Zhang, Q, 2008
)
" Increased production of ROS reduces the effect and/or bioavailability of NO, leading to an impaired endothelial function."( Raloxifene protects endothelial cell function against oxidative stress.
Au, CL; Chen, ZY; Cheng, CH; Gollasch, M; Huang, Y; Lau, CW; Leung, FP; Tsang, SY; Wong, CM; Yao, X; Yung, LM, 2008
)
" Findings suggest that DHA enhances eNOS and Akt activity, augments HSP90 expression, and increases NO bioavailability in response to Akt kinase activation."( Effects of dietary decosahexaenoic acid (DHA) on eNOS in human coronary artery endothelial cells.
Hart, CM; Knowlton, AA; Mbai, FN; Stebbins, CL; Stice, JP, 2008
)
"Metabolic syndrome (MetS) denotes a clustering of risk factors that may affect nitric oxide (NO) bioavailability and predispose to cardiovascular diseases, which are delayed by exercise training."( Enhanced concentrations of relevant markers of nitric oxide formation after exercise training in patients with metabolic syndrome.
Casella-Filho, A; Chagas, AC; Gomes, VA; Tanus-Santos, JE, 2008
)
"Reduced bioavailability of nitric oxide (NO) is a hallmark of diabetes mellitus-induced vascular complications."( Enhancement of endothelial nitric oxide synthase production reverses vascular dysfunction and inflammation in the hindlimbs of a rat model of diabetes.
Becher, PM; Mohr, Z; Peters, H; Riad, A; Rütten, H; Schultheiss, HP; Tschöpe, C; Uyulmaz, S; Van Linthout, S; Westermann, D; Wohlfart, P, 2008
)
"Application of BH4 in high doses is safe and enhances formation of cGMP, pointing to increased bioavailability of NO."( Effects of tetrahydrobiopterin on nitric oxide bioavailability and renal hemodynamics in healthy volunteers.
Artunc, F; Artunc, N; Boehmer, G; Erley, CM; Essig, M; Haering, HU; Plachtzik, C; Reich, M; Risler, T,
)
" In aged cells with an uncoupled NOS3 as shown by the reduced BH(4) level, the increase in superoxide anion and the lower production of cGMP and the decrease in NO bioavailability were linearly correlated with the increase in basal [Ca(2+)](i)."( Effect of uncoupling endothelial nitric oxide synthase on calcium homeostasis in aged porcine endothelial cells.
Boucher, JL; Fournet-Bourguignon, MP; Frapart, Y; Gosgnach, W; Lesage, L; Molez, S; Perrier, E; Reure, H; Royere, E; Vilaine, JP; Villeneuve, N, 2009
)
" We hypothesized that the relaxation to BAY 41-2272 is decreased in spontaneously hypertensive rats (SHR) because of the reduced NO bioavailability in this strain and that relaxation would be improved by inhibiting the oxidative stress."( Oxidative stress impairs vasorelaxation induced by the soluble guanylyl cyclase activator BAY 41-2272 in spontaneously hypertensive rats.
Priviero, FB; Teixeira, CE; Webb, RC; Zemse, SM, 2009
)
"Augmented oxidative stress in SHR impaired cGMP-dependent and -independent relaxation induced by BAY 41-2272, by decreasing NO bioavailability and sGC expression and by increasing contractile activity."( Oxidative stress impairs vasorelaxation induced by the soluble guanylyl cyclase activator BAY 41-2272 in spontaneously hypertensive rats.
Priviero, FB; Teixeira, CE; Webb, RC; Zemse, SM, 2009
)
"Starting from a non-selective pyrazolo-pyrimidone lead, the sequential use of parallel medicinal chemistry and directed synthesis led to the discovery of potent, highly selective, and orally bioavailable PDE9 inhibitors."( The discovery of potent, selective, and orally bioavailable PDE9 inhibitors as potential hypoglycemic agents.
Andrews, M; Bell, AS; Chen, Y; Deninno, MP; Eller-Zarbo, C; Eshelby, N; Etienne, JB; Michael Gibbs, E; Moore, DE; Palmer, MJ; Visser, MS; Yu, LJ; Zavadoski, WJ, 2009
)
"The status of nitric oxide (NO) in spontaneously hypertensive rats (SHR) is unclear and its bioavailability may be affected by imbalance with reactive oxygen species."( The effect of an NO donor, pentaerythrityl tetranitrate, on biochemical, functional, and morphological attributes of cardiovascular system of spontaneously hypertensive rats.
Cacányiová, S; Dovinová, I; Fáberová, V; Kristek, F, 2009
)
" Likely arachidonic acid reducing NO bioavailability through all these mechanisms could potentiate its platelet aggregating power."( The arachidonic acid effect on platelet nitric oxide level.
Leoncini, G; Segantin, A; Signorello, MG, 2009
)
" These data provide the first evidence that AM increases NO bioavailability in intact murine myocardium and confirm that the NO/sGC/cGMP pathway is central to the cytoprotective action of AM against ischaemia-reperfusion injury."( Nitric oxide/cGMP signalling mediates the cardioprotective action of adrenomedullin in reperfused myocardium.
Baxter, GF; Drexhage, C; Fowkes, RC; Hamid, SA; Rassaf, T; Thompson, I; Totzeck, M, 2010
)
" Our data suggest that the effect of the sex of the animal on NOS activity and expression is different in the three regions of the SHR kidney and supports the hypothesis that male SHR have lower NO bioavailability compared with females."( Renal NOS activity, expression, and localization in male and female spontaneously hypertensive rats.
Hyndman, KA; Pardieck, JL; Pollock, JS; Sullivan, JC, 2010
)
" This increase in nitric oxide bioavailability by the allyl sulfides was attenuated by wortmannin."( Diallyl disulfide and diallyl trisulfide protect endothelial nitric oxide synthase against damage by oxidized low-density lipoprotein.
Chen, HW; Lei, YP; Lii, CK; Liu, CT; Sheen, LY, 2010
)
"Hypercholesterolemia is associated with decreased nitric oxide (NO) bioavailability and endothelial dysfunction, a phenomenon thought to have a major role in the altered cerebral blood flow evident in stroke."( Alterations in nitric oxide and endothelin-1 bioactivity underlie cerebrovascular dysfunction in ApoE-deficient mice.
Ahluwalia, A; Duchene, J; Hattori, N; Milsom, AB; Panayiotou, C; Urabe, T; Yamashiro, K, 2010
)
" Emphasis was placed on the biphasic effects of the drugs on nitric oxide (NO) bioavailability and cytotoxicity, as well as drug interference with the interaction of endothelial NO synthase (eNOS) with caveolin-1 (Cav-1)."( Effects of statins on nitric oxide/cGMP signaling in human umbilical vein endothelial cells.
Mayer, B; Meda, C; Mykhaylyk, O; Plank, C; Schmidt, K,
)
" These results demonstrate that quercetin-mediated stimulation of eNOS phosphorylation increases NO bioavailability in endothelial cells and can thus play a role in the vascular protective effects associated with improved endothelial cell function."( Dietary flavonoid quercetin stimulates vasorelaxation in aortic vessels.
Constance, C; Inoue, T; Khoo, NK; Parks, DA; Patel, RP; Pozzo-Miller, L; White, CR; Zhou, F, 2010
)
" Endothelial dysfunction and reduced NO bioavailability have a central role in hypertension associated with pregnancy."( Characterization of the L-arginine-NO-cGMP pathway in spontaneously hypertensive rat platelets: the effects of pregnancy.
Brunini, TM; de Moura, RS; Matsuura, C; Mendes-Ribeiro, AC; Moss, MB; Ognibene, DT; Resende, AC, 2010
)
" Pharmacokinetic analysis of linaclotide showed very low oral bioavailability (0."( Linaclotide, through activation of guanylate cyclase C, acts locally in the gastrointestinal tract to elicit enhanced intestinal secretion and transit.
Bartolini, WP; Bryant, AP; Busby, RW; Cordero, EA; Currie, MG; Hannig, G; Kessler, MM; Kurtz, CB; Mahajan-Miklos, S; Pierce, CM; Solinga, RM; Sun, LJ; Tobin, JV, 2010
)
" The link between these risk factors and AD has yet to be identified; however, a common feature is endothelial dysfunction, specifically, decreased bioavailability of nitric oxide (NO)."( Endothelial nitric oxide modulates expression and processing of amyloid precursor protein.
Austin, SA; Katusic, ZS; Santhanam, AV, 2010
)
" We observed the establishment of two cardioprotective mechanisms and we suggest that these mechanisms could lead to increase intracellular cGMP: i) increased expression of BNP could increase "particulate" cGMP pool; ii) increased activation of AMPK, subsequent to increase in PDE4 activity and 5'AMP generation, could elevate "soluble" cGMP pool by enhancing NO bioavailability through NOX2 down-regulation."( Concerted regulation of cGMP and cAMP phosphodiesterases in early cardiac hypertrophy induced by angiotensin II.
Etienne-Selloum, N; Kane, MO; Keravis, T; Lugnier, C; Mokni, W; Schini-Kerth, VB; Walter, A, 2010
)
" The present study demonstrated that iNOS-derived superoxide generation was reduced, and that the NO bioavailability was increased, by treatment with the NOS-cofactor, tetrahydrobiopterin (BH4), before I/R in the hearts isolated from diabetic rats."( Reversal of inducible nitric oxide synthase uncoupling unmasks tolerance to ischemia/reperfusion injury in the diabetic rat heart.
Fujita, M; Ito, S; Iwasaka, T; Katano, T; Okazaki, T; Otani, H; Shimazu, T; Yoshioka, K, 2011
)
" We hypothesized that Ang II augmented PDE1 activation, decreasing the bioavailability of cyclic guanosine 3' 5'-monophosphate (cGMP), and contributing to increased vascular contractility."( Decreased cGMP level contributes to increased contraction in arteries from hypertensive rats: role of phosphodiesterase 1.
Carneiro, FS; Giachini, FR; Lima, VV; Tostes, RC; Webb, RC, 2011
)
"Diabetic EPCs demonstrate reduced eNOS expression and decreased NO bioavailability and migration in response to SDF-1α."( Blockade of NADPH oxidase restores vasoreparative function in diabetic CD34+ cells.
Caballero, S; Grant, MB; Jarajapu, YP; Li, Q; Lo, MC; Nakagawa, T; Verma, A, 2011
)
" NO bioavailability was assessed using cyclic guanosine monophosphate quantification."( Atorvastatin worsens left ventricular diastolic dysfunction and endothelial dysfunction of epicardial coronary arteries in normocholesterolemic porcine with left ventricular hypertrophy.
Aubin, MC; Carrier, M; Forcillo, J; Maltais, S; Perrault, LP; Shi, YF; Tardif, JC, 2011
)
" It is an important regulator of nitric oxide bioavailability and thus protects against vascular dysfunction."( Adeno-associated virus serotype 9-mediated overexpression of extracellular superoxide dismutase improves recovery from surgical hind-limb ischemia in BALB/c mice.
Annex, BH; French, BA; Katwal, AB; Lye, RJ; Prasad, KM; Sanders, JM; Saqib, A, 2011
)
" IH causes oxidative stress that may limit bioavailability of the endothelium-derived vasodilator nitric oxide (NO) and thus contribute to this hypertensive response."( Intermittent hypoxia augments pulmonary vascular smooth muscle reactivity to NO: regulation by reactive oxygen species.
Jernigan, NL; Kanagy, NL; Norton, CE; Resta, TC; Walker, BR, 2011
)
"Metabolic abnormalities as consequence of HFD cause platelet hyperaggregability involving enhanced intraplatelet ROS production and decreased NO bioavailability that appear to be accompanied by potential defects in the prosthetic haem group of soluble guanylyl cyclase."( Platelet hyperaggregability in high-fat fed rats: a role for intraplatelet reactive-oxygen species production.
Antunes, E; Calixto, MC; Delbin, MA; Lopes-Pires, ME; Marcondes, S; Monteiro, PF; Morganti, RP; Zanesco, A, 2012
)
" reduced bioavailability of nitric oxide (NO)."( Endothelial dysfunction enhances the pulmonary and systemic vasodilator effects of phosphodiesterase-5 inhibition in awake swine at rest and during treadmill exercise.
Beier, N; Duncker, DJ; Houweling, B; Merkus, D; Quispel, J; Verdouw, PD, 2012
)
" Such effects of ginsenosides including cardioprotective and anti-platelet activities have shown stability and bioavailability limitations."( Ginsenoside-Rp1 inhibits platelet activation and thrombus formation via impaired glycoprotein VI signalling pathway, tyrosine phosphorylation and MAPK activation.
Cho, JY; Endale, M; Kamruzzaman, SM; Kim, SD; Lee, WM; Park, HJ; Park, JY; Park, MH; Park, TY; Rhee, MH, 2012
)
" The impaired NO-sGC-cGMP pathway signaling in HF is secondary to reduced NO bioavailability and an alteration in the redox state of sGC, making it unresponsive to NO."( Soluble guanylate cyclase: a potential therapeutic target for heart failure.
Böhm, M; Burnett, JC; Butler, J; Campia, U; Cleland, JG; Collins, SP; Fonarow, GC; Gheorghiade, M; Greene, SJ; Levy, PD; Marti, CN; Metra, M; Pitt, B; Ponikowski, P; Roessig, L; Sabbah, HN; Sato, N; Stasch, JP; Voors, AA, 2013
)
" In cardiovascular diseases (CVDs), endothelial dysfunction with altered vascular reactivity is mostly attributed to decreased NO bioavailability via oxidative stress."( Soluble guanylyl cyclase is a target of angiotensin II-induced nitrosative stress in a hypertensive rat model.
Baskaran, P; Beuve, A; Couloubaly, S; Crassous, PA; Durán, WN; Fioramonti, X; Huang, C; Kim, DD; Papapetropoulos, A; Zhou, Z, 2012
)
" Both homozygous mutant (hph-1(-/-)) and heterozygous mutant (hph-1(+/-) mice) demonstrated reduction in GTP cyclohydrolase I activity and reduced bioavailability of BH(4)."( Uncoupling of eNOS causes superoxide anion production and impairs NO signaling in the cerebral microvessels of hph-1 mice.
d'Uscio, LV; Katusic, ZS; Santhanam, AV; Smith, LA, 2012
)
"We describe the discovery of potent and orally bioavailable tetrahydropyridopyrimidine inhibitors of phosphodiesterase 10A by systematic optimization of a novel HTS lead."( Discovery of tetrahydropyridopyrimidine phosphodiesterase 10A inhibitors for the treatment of schizophrenia.
Breslin, MJ; Coleman, PJ; Cox, CD; Fandozzi, C; Fuerst, J; Hill, N; Huszar, S; Kandebo, M; Kim, SH; Ma, B; McGaughey, G; Raheem, IT; Renger, JJ; Schreier, JD; Sharma, S; Smith, S; Uslaner, J; Yan, Y, 2012
)
": ED in middle-aged rats is associated with decreased NO bioavailability in erectile tissue due to upregulation of NADPH oxidase subunit gp91(phox) and downregulation of nNOS/p-eNOS."( Superoxide anion production by NADPH oxidase plays a major role in erectile dysfunction in middle-aged rats: prevention by antioxidant therapy.
Antunes, E; Báu, FR; Brugnerotto, AF; Mónica, FZ; Priviero, FB; Silva, FH; Toque, HA, 2013
)
" This study provides a direct link between oxidative stress and the enzymatic control of the NO bioavailability at the cellular level and endows with further insight into fundamental mechanisms underlying pancreatic disorders associated with disruptions in the L-arginine-NO-cGMP signalling enzyme cascade."( L-arginine-NO-cGMP signalling pathway in pancreatitis.
Bankfalvi, A; Boecker, W; Buchwalow, I; Neumann, J; Poremba, C; Samoilova, V; Schleicher, C; Schnekenburger, J; Tiemann, K, 2013
)
" When NO formation or bioavailability is decreased by oxidative stress and PDE-5 inhibitors are no longer effective, a new class of agents called soluble guanylate cyclase (sGC) stimulators like BAY 41-8543 will induce erection."( Modulation of soluble guanylate cyclase for the treatment of erectile dysfunction.
Kadowitz, PJ; Lasker, GF; Pankey, EA, 2013
)
" Considering the role of reactive oxygen species (ROS) in the uncoupling of eNOS, we hypothesized that the preadministration of an antioxidant as tempol, could improve the hypotensive response of nebivolol in normotensive animals increasing the nitric oxide (NO) bioavailability by a reduction of superoxide (O2(•-)) basal level production in the vascular tissue."( Tempol-nebivolol therapy potentiates hypotensive effect increasing NO bioavailability and signaling pathway.
Balestrasse, KB; Bertera, FM; Gorzalczany, SB; Höcht, C; Polizio, AH; Santa-Cruz, DM; Taira, CA, 2014
)
" Thus, our data suggests that reactive oxygen species may regulate food intake through modulating the bioavailability of nitric oxide."( The role of nitric oxide signaling in food intake; insights from the inner mitochondrial membrane peptidase 2 mutant mice.
Han, C; Lu, B; Zhao, Q, 2013
)
"Nitric oxide (NO) bioavailability is reduced in the setting of heart failure."( Nitrite therapy improves left ventricular function during heart failure via restoration of nitric oxide-mediated cytoprotective signaling.
Bhushan, S; Butler, J; Calvert, JW; Georgiopoulou, VV; Huang, H; Kondo, K; Lefer, DJ; Murohara, T; Nicholson, CK; Otsuka, H; Polhemus, DJ; Tao, YX, 2014
)
"No evidence exists as to whether increasing NO bioavailability via nitrite therapy attenuates heart failure severity after pressure-overload-induced hypertrophy."( Nitrite therapy improves left ventricular function during heart failure via restoration of nitric oxide-mediated cytoprotective signaling.
Bhushan, S; Butler, J; Calvert, JW; Georgiopoulou, VV; Huang, H; Kondo, K; Lefer, DJ; Murohara, T; Nicholson, CK; Otsuka, H; Polhemus, DJ; Tao, YX, 2014
)
"There is a mismatch between the results obtained from isolated vessel rings and cultured endothelial cells suggesting TNF-α may reduce the biological effect of NO by reducing its bioavailability rather than its formation, leading to endothelial cell dysregulation."( The effect of tumour necrosis factor-α and insulin on equine digital blood vessel function in vitro.
Bailey, SR; Elliott, J; Harris, PA; Menzies-Gow, NJ; Wray, H, 2014
)
" Our data suggest that increasing the bioavailability of cGMP might be beneficial in ameliorating the inflammation associated with sepsis."( Shedding of the tumor necrosis factor (TNF) receptor from the surface of hepatocytes during sepsis limits inflammation through cGMP signaling.
Billiar, TR; Deng, M; Loughran, PA; Scott, MJ; Zhang, L, 2015
)
" Our results demonstrate that preservation of NO bioavailability leads to renal protection in AA-induced acute kidney injury by reducing oxidative stress and maintaining renal function."( Protective effect of nitric oxide in aristolochic acid-induced toxic acute kidney injury: an old friend with new assets.
Caron, N; Colombaro, V; Declèves, AÉ; Jadot, I; Martin, B; Nortier, J; Voisin, V, 2016
)
" Dysfunction in the production and/or the bioavailability of NO characterizes endothelial dysfunction, which is associated with cardiovascular diseases such as hypertension and atherosclerosis."( Vascular nitric oxide: Beyond eNOS.
Leung, SW; Vanhoutte, PM; Zhao, Y, 2015
)
" The bioavailability of IGF-1 at both mRNA and protein levels were measured by quantitative real-time PCR and Western blot respectively."( Decrease of the insulin-like growth factor-1 bioavailability in spontaneously hypertensive rats with erectile dysfunction.
Cheng, SP; Huang, H; Huang, JB; Liu, RH; Mao, FJ; Pan, H; Sun, YL; Xiao, S; Zhong, GJ; Zhou, ZY, 2016
)
" Thus, since acetylcholine-induced NO-mediated relaxation was impaired in diabetes because of reduced eNOS protein expression, pharmacological intervention improving NO bioavailability could be useful in the management of diabetic endothelial dysfunction."( Reduced nitric oxide-mediated relaxation and endothelial nitric oxide synthase expression in the tail arteries of streptozotocin-induced diabetic rats.
Leung, SW; Mokhtar, SS; Rasool, AH; Suppian, R; Vanhoutte, PM; Yusof, MI, 2016
)
" A decrease in nitric oxide (NO) bioavailability has been pointed out to play a major role in this phenomenon."( Combined effects of aerobic exercise and l-arginine ingestion on blood pressure in normotensive postmenopausal women: A crossover study.
de P Novais, I; Katsanos, CS; Puga, GM; Zanesco, A, 2016
)
" Canonical vasodilator therapy involving the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cGMP pathway has demonstrated efficacy, but in pathologic states, endothelial dysfunction within the pulmonary vasculature leads to the reduced synthesis and bioavailability of NO."( Soluble Guanylate Cyclase Stimulators and Activators: Novel Therapies for Pulmonary Vascular Disease or a Different Method of Increasing cGMP?
Kadowitz, P; Koress, C; Swan, K, 2016
)
" The diminished NO bioavailability associated with inflammatory status and impaired enzymatic antioxidant defence may contribute to future cardiovascular complications in obesity."( Platelet hyperaggregability in obesity: is there a role for nitric oxide impairment and oxidative stress?
Brunini, TM; Leite, NR; Matsuura, C; Mendes-Ribeiro, AC; Mury, WV; Noronha Filho, G; Perszel, MB; Siqueira de Medeiros, M, 2016
)
" We previously demonstrated that, through increased phosphatidylserine membrane exposure, ESRD-RBCs augmented their adhesion to human cultured endothelium, in which NO bioavailability decreased."( Nitric oxide synthetic pathway and cGMP levels are altered in red blood cells from end-stage renal disease patients.
Bonomini, M; Cortese-Krott, MM; Csonka, C; Di Pietro, N; Di Silvestre, S; Di Tomo, P; Ferdinandy, P; Gazzano, E; Giardinelli, A; Kelm, M; Pandolfi, A; Panknin, C; Riganti, C; Sirolli, V, 2016
)
" In this clinical study, we investigated whether PD-mediated impairment of nitric oxide (NO) bioavailability and signaling, in patients with persistently low systolic blood pressure (SBP), can explain the occurrence of cerebral ischemia."( Peritoneal dialysis impairs nitric oxide homeostasis and may predispose infants with low systolic blood pressure to cerebral ischemia.
Bárány, P; Békássy, Z; Cananau, C; Carlström, M; Checa, A; Hansson, S; Krmar, RT; Lundberg, JO; Sartz, L; Svensson, A; Weitzberg, E; Westphal, S; Wheelock, CE; Wide, K, 2016
)
" Therapeutic strategies that benefit NO bioavailability have been applied in clinical medicine extensively."( The Endothelium-Dependent Nitric Oxide-cGMP Pathway.
Bian, K; Mónica, FZ; Murad, F, 2016
)
"There is increasing evidence that the permeability of the glomerular filtration barrier (GFB) is partly regulated by a balance between the bioavailability of nitric oxide (NO) and that of reactive oxygen species (ROS)."( Nitric oxide synthase inhibition causes acute increases in glomerular permeability in vivo, dependent upon reactive oxygen species.
Dolinina, J; Öberg, CM; Rippe, A; Rippe, B; Sverrisson, K, 2016
)
" Thus our results suggest that, in this AD mouse model, dysfunction of large intracranial, extracerebral arteries important for brain perfusion is mediated by reduced NO bioavailability rather than by CAA."( Reduced nitric oxide bioavailability mediates cerebroarterial dysfunction independent of cerebral amyloid angiopathy in a mouse model of Alzheimer's disease.
Akhmedov, A; Camici, GG; Derungs, R; Keller, S; Kulic, L; Lüscher, TF; Merlini, M; Nitsch, RM; Savarese, G; Shi, Y; Spescha, RD, 2017
)
" The in vitro experiments showed that OB-plasma significantly impaired endothelial insulin-stimulated NO production and bioavailability compared to CTRL-plasma."( Plasma from pre-pubertal obese children impairs insulin stimulated Nitric Oxide (NO) bioavailability in endothelial cells: Role of ER stress.
Bologna, G; Chiarelli, F; Cordone, VGP; de Giorgis, T; Di Pietro, N; Di Silvestre, S; Lanuti, P; Marcovecchio, ML; Mohn, A; Pandolfi, A, 2017
)
" A number of studies suggest that the bioavailability of nitric oxide is reduced in patients with pulmonary vascular disease and that augmentation of the nitric oxide/cGMP pathway may be an effective strategy for treatment."( The Nitric Oxide Pathway in Pulmonary Vascular Disease.
Kadowitz, PJ; Klinger, JR, 2017
)
"It is widely accepted that impaired bioavailability of endothelial nitric oxide (NO) plays a critical role in the pathophysiology of pulmonary arterial hypertension (PAH)."( Inhibition of nitric oxide synthase unmasks vigorous vasoconstriction in established pulmonary arterial hypertension.
Abe, K; Hoka, S; Ishikawa, T; McMurtry, IF; Oka, M; Saku, K; Sunagawa, K; Tanaka, M; Tsutsui, H; Yoshida, K, 2017
)
" Since excess hemoglobin in the plasma causes reduced nitric oxide (NO) bioavailability and oxidative stress, we hypothesized that esophageal contraction may be impaired by intravascular hemolysis."( Impairment of Nitric Oxide Pathway by Intravascular Hemolysis Plays a Major Role in Mice Esophageal Hypercontractility: Reversion by Soluble Guanylyl Cyclase Stimulator.
Beraldi Calmasini, F; Costa Alexandre, E; Fernanda Franco-Penteado, C; Ferreira Costa, F; Henrique Silva, F; Yotsumoto Fertrin, K, 2018
)
"A decrease in BUBR1 reduced eNOS bioavailability through a pathway other than eNOS phosphorylation."( BUBR1 Insufficiency Is Correlated with eNOS Reduction Experimentally
Furuyama, T; Jogo, T; Kawakubo, E; Maehara, Y; Matsumoto, T; Oda, Y; Oki, E; Saeki, H; Yamashita, S; Yoshiya, K, 2018
)
" However, the bioavailability of iron is low due to its insolubility under aerobic conditions."( The Iron Tug-of-War between Bacterial Siderophores and Innate Immunity.
Golonka, R; Vijay-Kumar, M; Yeoh, BS, 2019
)
"This study aims at improving the bioavailability of a poorly soluble phosphodiesterase-5 inhibitor; tadalafil (TD) via developing intranasal (IN) nanoemulsions (NEs)."( Intranasal Tadalafil nanoemulsions: formulation, characterization and pharmacodynamic evaluation.
Abdelmonsif, DA; Boraie, N; Elbardisy, B; Galal, S, 2019
)
"The hypothesis of decreased nitric oxide (NO) bioavailability in sickle cell disease (SCD) proposes that multiple factors leading to decreased NO production and increased consumption contributes to vaso-occlusion, pulmonary hypertension, and pain."( Sickle cell disease subjects and mouse models have elevated nitrite and cGMP levels in blood compartments.
Almeida, LEF; Darbari, DS; de Souza Batista, CM; Finkel, JC; Kamimura, S; Nettleton, MY; Quezado, ZMN; Smith, ML; Spornick, N; Wakim, P; Walek, E, 2020
)
" In the present study, we investigate the cellular action of exogenous NO in the hypoxia-mediated diminution of cell-matrix adhesion of PBMNC and NO bioavailability in vitro."( Nitric oxide restores peripheral blood mononuclear cell adhesion against hypoxia via NO-cGMP signalling.
Behera, J; Chatterjee, S; Keshri, GK; Kumar, R; Nagarajan, S; Saran, U; Suryakumar, G, 2020
)
" Bioavailability and food effects on vericiguat PK (IR tablets) were also studied in European subjects."( Safety, pharmacodynamic, and pharmacokinetic characterization of vericiguat: results from six phase I studies in healthy subjects.
Arens, E; Becker, C; Boettcher, M; Loewen, S; Mueck, W; Thomas, D; Yoshikawa, K, 2021
)
"0 mg IR tablets with food increased bioavailability by 19% (estimated ratio 119% [90% confidence interval]: 108; 131]), reduced PK variability, and prolonged vericiguat absorption relative to the fasted state."( Safety, pharmacodynamic, and pharmacokinetic characterization of vericiguat: results from six phase I studies in healthy subjects.
Arens, E; Becker, C; Boettcher, M; Loewen, S; Mueck, W; Thomas, D; Yoshikawa, K, 2021
)
" Thus, impaired production or reduced bioavailability of NO predisposes to the onset of different cardiovascular (CV) diseases."( Novel Insights Regarding Nitric Oxide and Cardiovascular Diseases.
Costa, D; Infante, T; Napoli, C, 2021
)
"Metabolic syndrome is linked to an increased risk of cardiovascular complications by a mechanism involving mainly decreased nitric oxide (NO) bioavailability and impaired NO-soluble guanylate cyclase (sGC)- cyclic guanosine monophosphate (cGMP) signalling (NO-sGC-cGMP)."( Soluble guanylate cyclase chronic stimulation effects on cardiovascular reactivity in cafeteria diet-induced rat model of metabolic syndrome.
Desfontis, JC; Doghri, Y; Dubreil, L; Fleurisson, R; Hélissen, O; Lalanne, V; Mallem, MY; Thorin, C, 2021
)
" Bay 58-2667 (cinaciguat) is able to re-activate defective sGC; however, the drug suffers from poor bioavailability and its systemic administration is linked to adverse events such as severe hypotension, which can hamper the therapeutic effect."( Targeted Delivery of Soluble Guanylate Cyclase (sGC) Activator Cinaciguat to Renal Mesangial Cells via Virus-Mimetic Nanoparticles Potentiates Anti-Fibrotic Effects by cGMP-Mediated Suppression of the TGF-β Pathway.
Fleischmann, D; Goepferich, A; Harloff, M; Maslanka Figueroa, S; Schlossmann, J, 2021
)
"Soluble guanylate cyclase (sGC) plays an important role in nitric oxide (NO)-mediated regulation of vascular tone; however, NO bioavailability is often reduced in diseased blood vessels."( Soluble Guanylate Cyclase-Mediated Relaxation in Aortas from Rats with Renovascular Hypertension.
Nakagawa, K; Ohkita, M; Okamura, T; Shimosato, T; Tawa, M, 2022
)
" However, a small molecule that is orally bioavailable and directly targets the GC-A to potentiate cGMP has yet to be discovered."( Discovery of small molecule guanylyl cyclase A receptor positive allosteric modulators.
Burnett, JC; Hershberger, PM; Hood, BL; Kirby, RJ; Malany, S; Maloney, PR; Mose-Yates, H; Pan, S; Peddibhotla, S; Sangaralingham, SJ; Sessions, HE; Vasile, S; Whig, K; Zheng, Y, 2021
)
" We herein report the identification of BAY-7081, a potent, selective, and orally bioavailable PDE9A inhibitor with very good aqueous solubility starting from a high-throughput screening hit."( BAY-7081: A Potent, Selective, and Orally Bioavailable Cyanopyridone-Based PDE9A Inhibitor.
Andreevski, AL; Anlauf, S; Bogner, P; Dieskau, AP; Dreher, J; Eitner, F; Fliegner, D; Follmann, M; Gericke, KM; Maassen, S; Meibom, D; Meyer, J; Micus, S; Schlemmer, KH; Steuber, H; Tersteegen, A; von Buehler, CJ; Wunder, F, 2022
)
" The present review aims to examine the molecular mechanisms involved in the bioavailability of NO and its modulation of downstream pathways."( Modulation of the nitric oxide/cGMP pathway in cardiac contraction and relaxation: Potential role in heart failure treatment.
Bava, I; Carresi, C; Federici, M; Gliozzi, M; Macrì, R; Maiuolo, J; Mollace, R; Mollace, V; Muscoli, C; Muscoli, S; Musolino, V; Palma, E; Salvemini, D; Scarano, F; Tavernese, A, 2023
)

Dosage Studied

Cyclic GMP dose-response curves to CNP failed to show any signs of saturation even at concentrations up to 30 microM, indicating a relatively low affinity of CNP for the GC-B receptor. Preincubation of contracted artery rings with GTP (100 microM) or guanosine before eliciting relaxations with nitrovasodilators significantly shifted the dose- response curves of nitrocompounds to the left.

ExcerptReference
" The psychotropic drugs tested blocked the muscarinic receptor and equilibrium dissociation constants (KB) were calculated from the parallel displacement of dose-response curves."( Blockade by psychotropic drugs of the muscarinic acetylcholine receptor in cultured nerve cells.
Divinetz-Romero, S; Richelson, E, 1977
)
" Dose-response curves to hormones, fluoride, and GMP-P (NH)P were not affected by age."( Hormone-sensitive fat cell adenylate cyclase in the rat. Influences of growth, cell size, and aging.
Cooper, B; Gregerman, RI, 1976
)
" Dose-response relationships for isoproterenol (IP) reveal a noncompetitive inhibition of the inotropic action of the catecholamine by ACh."( Catecholamine antagonism of acetylcholine and dibutyrl guanosine 3',-5'-monophosphate in the mammalian ventricular myocardium.
Jacob, R; Schwegler, M, 1975
)
" No acitvity was detected in other brain areas at various dosed or incubation times."( Effects of kainic acid, a cyclic analogue of glutamic acid, on cyclic nucleotide accumulation in slices of rat cerebellum.
Molloy, BB; Ryan, JJ; Schmidt, MJ, 1976
)
" For both CCK-OP and carbamylcholine there was close agreement between the dose-response curve for stimulation of calcium outflux and that for increase of cellular cyclic GMP."( Action of cholecystokinin, cholinergic agents, and A-23187 on accumulation of guanosine 3':5'-monophosphate in dispersed guinea pig pancreatic acinar cells.
Christophe, JP; Conlon, TP; Frandsen, EK; Gardner, JD; Krishna, G, 1976
)
" Noncyclic nucleotides, adenosine, adenosine 5'-monophosphate (AMP), and guanosine 5'-monophosphate (GMP) showed clear, dose-response protection against histamine death of propranolol-treated mice when they were given 45 to 90 min before histamine."( Hypersensitivity to histamine and systemic anaphylaxis in mice with pharmacologic beta adrenergic blockade: protection by nucleotides.
Matsumura, Y; Tan, EM; Vaughan, JH, 1976
)
" Sensitivity of JV measurement was improved by using each punctured tubule for control measurements: 1) Parathyroid hormoen (PTH) on the contraluminal cell side reduced JV in a dose-response behavior."( Effect of parathyroid hormone and cyclic adenosine 3',5'-monophosphate on isotonic fluid reabsorption: polarity of proximal tubular cells.
Baumann, K; Bode, F; Chan, YL; Papavassiliou, F, 1977
)
"The genome of Drosophila melanogaster has been surveyed for chromosomal regions which exert a dosage effect on the activities of cAMP phosphodiesterase or cGMP phosphodiesterase."( A cytogenetic analysis of cyclic nucleotide phosphodiesterase activities in Drosophila.
Golanty, E; Kiger, JA, 1977
)
"In rabbits the topical administration of sodium azide (NaNs) or sodium nitroprusside (SNP) increased intraocular pressure in a dose-response manner."( Increased intraocular pressure following topical azide or nitroprusside.
Becker, B; Fritz, C; Holmberg, N; Krupin, T; Weiss, A, 1977
)
" This toxin produced a time and dose-related increase in pacemaker rate and cyclic adenosine 3':5'-monophosphate (cyclic AMP) levels and shifted to the left the dose-response curves of norepinephrine on the pacemaker rate and cyclic AMP content in the S-A node."( Effect of cholera enterotoxin on pacemaker rate and cyclic adenosine 3':5'-monophosphate in isolated rabbit sinoatrial node.
Fujiwara, M; Hidaka, H; Lee, JJ; Taniguchi, T, 1979
)
" CGS 15943 (100 nM), a nonselective adenosine antagonist, attenuated the VR activity of DPMA and CPA, causing a 9- and 12-fold rightward shift of the dose-response curves, respectively, whereas 8-cyclopentyl-1,3-dipropylxanthine (20 nM), a highly A1-selective blocker, had no such effect."( Demonstration of vasorelaxant activity with an A1-selective adenosine agonist in porcine coronary artery: involvement of potassium channels.
Cox, BF; Lappe, RW; Merkel, LA; Perrone, MH; Rivera, LM, 1992
)
" bolus injections of urodilatin at doses of 1, 2 or 4 micrograms kg-1 body weight (bw) (n = 6 per dosage group)."( Haemodynamic and renal effects of urodilatin in healthy volunteers.
Drummer, C; Gerzer, R; Kentsch, M; Ludwig, D; Müller-Esch, G, 1992
)
" The dose-response curves showed that L-arginine significantly decreased arterial pressure and increased heart rate."( Evidence for normal nitric oxide-mediated vasodilator tone in conscious rats with cirrhosis.
Cailmail, S; Hadengue, A; Lebrec, D; Moreau, R; Oberti, F; Ohsuga, M; Pussard, E; Sogni, P, 1992
)
" Simultaneously, a dose-response diuretic and natriuretic effect was observed with all the aminoacids."( Renal and systemic effects of aminoacids administered separately: comparison between L-arginine and non-nitric oxide donor aminoacids.
Caramelo, C; Casado, S; Cernadas, MR; Digiuni, E; Espinosa, G; Gallego, MJ; Hernando, L; López-Farré, A; Riesco, A, 1992
)
" The NTG dose-response curve shifted markedly to the right, but the ACh dose-response curve shifted to the left after the induction of NTG tolerance."( Acetylcholine-induced endothelium-dependent vascular smooth muscle relaxation in nitroglycerin-tolerant isolated rat aorta.
Aikawa, J; Akatsuka, N; Machii, K; Moroi, M; Namiki, A, 1991
)
" The dose-response curves of forearm blood flow and of forearm vascular resistance after increasing infusion rates of atrial natriuretic factor were shifted to the right in the elderly when compared with the young subjects."( Attenuated forearm vasodilator response to atrial natriuretic factor in the elderly.
Jansen, TL; Smits, P; Tan, AC; Thien, T, 1991
)
" dose-response manner 30 min after pretreatment with NNA (1 or 3 mg/kg) or saline (1 ml/kg)."( N omega-nitro-L-arginine attenuates the accumulation of aortic cyclic GMP and the hypotension produced by zaprinast.
Buchholz, RA; Dundore, RL; O'Connor, B; Pagani, ED; Pratt, PF, 1991
)
" Parenteral injections of D-cycloserine produced a biphasic dose-response curve which suggested partial agonism."( Actions of D-cycloserine at the N-methyl-D-aspartate-associated glycine receptor site in vivo.
Cler, JA; Emmett, MR; Iyengar, S; Mick, SJ; Rao, TS; Wood, PL, 1991
)
" Dose-response studies reveal that 10(-6) to 10(-4) M concentrations of 8-bromo-cAMP (8-Br-cAMP) elicit a maximal response."( Progesterone receptor regulation in uterine cells: stimulation by estrogen, cyclic adenosine 3',5'-monophosphate, and insulin-like growth factor I and suppression by antiestrogens and protein kinase inhibitors.
Aronica, SM; Katzenellenbogen, BS, 1991
)
" The possibility of once-daily dosing may prove useful with respect to drug compliance in the long-term treatment of a generally asymptomatic disease such as hypertension."( Arterial vasodilator and antihypertensive effects of diltiazem.
Bühler, FR; Kiowski, W; Linder, L, 1990
)
" Preincubation of contracted artery rings with GTP (100 microM) or guanosine (100 microM) before eliciting relaxations with nitrovasodilators significantly shifted the dose-response curves of nitrocompounds to the left and augmented the increases in cyclic GMP."( Modification of nitrovasodilator effects on vascular smooth muscle by exogenous GTP and guanosine.
Laustiola, KE; Manninen, V; Metsä-Ketelä, T; Pörsti, I; Vapaatalo, H; Vuorinen, P, 1991
)
" Doubling the dosage of drug (2-mg/kg bolus, 6 mg/kg."( In vivo and in vitro studies of a putative inhibitor of cyclic guanosine 3',5'-monophosphate production.
Brandt, MA; Conrad, KP, 1991
)
" Inhibition by cAMP was achieved by shifting the Ca2+ dose-response curve for secretion to the right; this was observed for the release of both specific granules (vitamin B12 binding protein) and azurophil granules (B-glucuronidase)."( Cyclic AMP inhibits secretion from electroporated human neutrophils.
Kuczynski, B; Smolen, JE; Stoehr, SJ, 1991
)
" However, following intracerebroventricular administration (100-500 micrograms/rat), tiletamine increased pyriform cortical DA metabolism with a bell-shaped dose-response curve."( Contrasting neurochemical interactions of tiletamine, a potent phencyclidine (PCP) receptor ligand, with the N-methyl-D-aspartate-coupled and -uncoupled PCP recognition sites.
Cler, JA; Contreras, PC; Dilworth, VM; Iyengar, S; Mick, SJ; Monahan, JB; Rao, TS; Wood, PL, 1991
)
" The icb dose-response data indicated a unimolecular interaction for these compounds."( Glycine, glycinamide and D-serine act as positive modulators of signal transduction at the N-methyl-D-aspartate (NMDA) receptor in vivo: differential effects on mouse cerebellar cyclic guanosine monophosphate levels.
Cler, JA; Emmett, MR; Iyengar, S; Mick, SJ; Rao, TS; Wood, PL, 1990
)
" A four-point dose-response curve was prepared for dopexamine from 1 microgram/kg/min to 4 micrograms/kg/min."( [Acute reduction of increased atrial natriuretic peptide level and cyclic guanosine monophosphate in patients with chronic heart failure caused by beta-adrenergic stimulation with dopexamine hydrochloride. Correlation with hemodynamic parameters].
Baumann, G; Blömer, H; Gerzer, R; Kerscher, M; Stangl, K; Weil, J, 1990
)
" Dose-response curves for whole cell cGMP production and membrane guanylate cyclase activity in response to ANF were closely related."( Atrial natriuretic factor activates membrane-bound guanylate cyclase of chief cells.
Cherner, JA; Naik, L; Singh, G, 1990
)
" Further elucidation of the possible role of BNP as a circulating hormone in man awaits measurement of tissue and plasma concentrations of human BNP in health and disease and provision of fuller dose-response data for human as well as porcine BNP."( Brain natriuretic peptide administered to man: actions and metabolism.
Espiner, E; Ikram, H; McGregor, A; Richards, M; Yandle, T, 1990
)
" Upon stimulation with bradykinin, amounts of endogenously formed NO were within the same range as the dose-response curves for exogenously applied NO both for changes in coronary resistance and cGMP release."( Control of coronary vascular tone by nitric oxide.
Kelm, M; Schrader, J, 1990
)
" In nine healthy human volunteers who had received a low oral dosage of sinorphan or retorphan in a double-blind, placebo-controlled, randomized trial, sinorphan was also 2-3 fold more potent than retorphan in inhibiting plasma enkephalinase activity."( Stereoselective protection of exogenous and endogenous atrial natriuretic factor by enkephalinase inhibitors in mice and humans.
Ardaillou, R; Baumer, P; Chaignon, B; Cournot, A; Duchier, J; Dussaule, JC; Gros, C; Lecomte, JM; Lim, C; Souque, A, 1990
)
" Gene dosage effects have been shown for some of these enzymes, including SOD-1."( Cyclic guanosine monophosphate metabolism in human amnion cells trisomic for chromosome 21.
Andersson, RG; Axelsson, KL; Karlsson, JO; Sjöstedt, A; Wahlström, J, 1990
)
" An evaluation of the parenteral dose-response curve for HA-966, revealed no effect on basal activity within the cerebellum."( In vivo antagonism of agonist actions at N-methyl-D-aspartate and N-methyl-D-aspartate-associated glycine receptors in mouse cerebellum: studies of 1-hydroxy-3-aminopyrrolidone-2.
Cler, J; Emmett, MR; Iyengar, S; Mick, S; Oei, E; Rao, TS; Wood, PL, 1990
)
"12 in rat vascular smooth muscle cells and shifts the ANP/cGMP dose-response curve by 3 orders of magnitude at a 10 microM concentration."( Atrial natriuretic peptide antagonists: biological evaluation and structural correlations.
Budzik, GP; Dillon, TP; Holleman, WH; Holst, MA; Kiso, Y; Novosad, EI; Opgenorth, TJ; Rockway, TW; Thomas, AM; von Geldern, TW, 1990
)
" At peptide concentrations of 1 microM clear-cut plateaus of the dose-response curves are not yet reached."( Atrial natriuretic hormones raise the level of cyclic GMP in neural cell lines.
Friedl, A; Hamprecht, B; Harmening, C, 1986
)
" The dose-response relationships for enoximone were always less steep than those for IBMX."( Effects of enoximone and isobutylmethylxanthine on contractile tension and cyclic nucleotide levels in isolated blood-perfused dog papillary muscle.
Dage, RC; Hsieh, CP; Kariya, T; Ruberg, SJ, 1987
)
" The dose-response curve for cyclic AMP on ICa was well fitted by the Michaelis equation with a K50 (i."( Cyclic guanosine 3',5'-monophosphate regulates the calcium current in single cells from frog ventricle.
Fischmeister, R; Hartzell, HC, 1987
)
" Dose-response curves for the relaxing and cyclic guanosine monophosphate (cGMP) increasing effects of nicorandil were obtained in isolated strips of bovine coronary arteries and compared with those of other nitrovasodilatators."( Cyclic GMP in nicorandil-induced vasodilatation and tolerance development.
Holzmann, S; Kukovetz, WR, 1987
)
"The natriuretic agent amiloride induces a shift of the dose-response curve of particulate guanylate cyclase to atrial natriuretic factor (ANF) to the left."( Amiloride increases the sensitivity of particulate guanylate cyclase to atrial natriuretic factor.
Gerzer, R; Heim, JM; Ivanova, K, 1988
)
" MIX at 100 microM potentiated the effects of submaximal doses of isoproterenol and shifted the dose-response curve for cAMP to the left but did not affect the dose-response curve for 8-bromo-cAMP."( Role of phosphodiesterase in regulation of calcium current in isolated cardiac myocytes.
Hartzell, HC; Simmons, MA, 1988
)
" Methylene blue also caused 10 fold and 100 fold rightward shifts in the dose-response curves of MY-5445 and vinpocetine, respectively."( Role of selective cyclic GMP phosphodiesterase inhibition in the myorelaxant actions of M&B 22,948, MY-5445, vinpocetine and 1-methyl-3-isobutyl-8-(methylamino)xanthine.
Brazdil, R; Diocee, BK; Jordan, R; Souness, JE, 1989
)
" Furthermore, the inhibition of 45Ca2+ uptake and of fluorescence increase observed in the presence of extracellular Ca2+ displayed remarkably parallel dose-response curves, suggesting that elevation of cyclic GMP brought about by SIN-1 inhibits the opening of "receptor-operated channels" whose precise nature remains to be determined."( Inhibition of calcium influx in thrombin-stimulated platelets by SIN-1, an activator of soluble guanylate cyclase.
Chap, H; Simon, MF, 1989
)
" As a result, the dose-response curve of SIN-1 was shifted to the left."( Interaction between SIN-1 and prostacyclin in inhibiting platelet aggregation.
Bult, H; Fret, HR; Herman, AG, 1989
)
" When the strips were treated with submaximal effective concentrations of NO, some tolerance was observed, as shown by moderate attenuation of the rises in cyclic GMP, and a rightward shift of the dose-response curve of the relaxing effects by a dose factor of 10 (DF = 10)."( Tolerance and cross-tolerance between SIN-1 and nitric oxide in bovine coronary arteries.
Holzmann, S; Kukovetz, WR, 1989
)
" In isolated aortic strips, dose-response curves with acetylcholine and LPC showed diminished relaxation in atherosclerotic preparations, and cyclic GMP production following LPC was reduced."( Effect of lysophosphatidylcholine on atherosclerotic rabbit arteries.
Bing, RJ; Menon, NK; Saito, T; Wolf, A; Zehetgruber, M, 1989
)
" The dose-response of stimulation of Ca2+ uptake with cGMP indicated an ED50 of 5 nM cGMP."( Cyclic guanosine monophosphate-enhanced sequestration of Ca2+ by sarcoplasmic reticulum in vascular smooth muscle.
Twort, CH; van Breemen, C, 1988
)
" Neurotensin preincubation with intact N1E-115 cells for increasing lengths of time caused time-dependent shifts to the right of the dose-response curve and reductions in the maximum cyclic GMP response."( Desensitization of neurotensin receptor-mediated cyclic GMP formation in neuroblastoma clone N1E-115.
Gilbert, JA; Richelson, E; Strobel, TR, 1988
)
" ANP stimulated production of cyclic GMP (cGMP), and inhibited aldosterone secretion with a similar dose-response relationship."( Regulation of aldosterone secretion by avian adrenocortical cells.
Hurwitz, S; Pines, M; Rosenberg, J, 1988
)
" Dose-response curves revealed that maximal stimulation of guanylate cyclase by EGF occurred at 1 nM."( Epidermal growth factor enhances guanylate cyclase activity in vivo and in vitro.
Scheving, LA; Scheving, LE; Tsai, TH; Vesely, DL, 1985
)
" The implications of these results are that, in slices, cellular uptake is responsible for (i) the dose-response curves to L-glutamate, L- and D-aspartate bearing little or no relationship to the true (or relative) potencies of these amino acids; (ii) the potency of APV towards the actions of transported agonists acting at NMDA receptors being reduced and (iii) a differential sensitivity to APV of responses to L-glutamate and L-aspartate being created, the consequence being that a potent action of L-glutamate on NMDA receptors is disguised."( Cellular uptake disguises action of L-glutamate on N-methyl-D-aspartate receptors. With an appendix: diffusion of transported amino acids into brain slices.
Garthwaite, J, 1985
)
" Dose-response curves were constructed for the increase in cGMP-immunofluorescence intensity for K+ and carbachol."( Single cell quantitative immunocytochemistry of cyclic GMP in the superior cervical ganglion of the rat.
Garssen, J; Schipper, J; Steinbusch, HW; Tilders, FJ; Vente, JD, 1987
)
" The similar dose-response relationships for binding, guanylate cyclase stimulation by STa, and cGMP production suggest that the guanylate cyclase-cGMP system is coupled to ST occupancy of specific receptors."( T84 cell receptor binding and guanyl cyclase activation by Escherichia coli heat-stable toxin.
Cohen, M; Dharmsathaphorn, K; Giannella, R; Guarino, A; Thompson, M, 1987
)
" In vitro studies with adult control retinas incubated with 10(-9)-10(-4) M lead revealed a dose-response inhibition (10-40%) of cGMP-PDE between 10(-6)- and 10(-4) M lead and stimulation of guanylate cyclase (20-158%) only above 10(-4) M lead, indicating that cGMP-PDE is more sensitive to the direct effects of lead than the synthetic cGMP enzyme."( Rods are selectively altered by lead: I. Electrophysiology and biochemistry.
Farber, DB; Fox, DA, 1988
)
" Incubation of cells with pertussis toxin, however, did not significantly alter the dose-response curve for carbamylcholine effects on cGMP."( Effects of pertussis toxin on cAMP and cGMP responses to carbamylcholine in N1E-115 neuroblastoma cells.
Bruni, P; Burns, DL; Hewlett, EL; Moss, J, 1985
)
" Pulse rate, blood pressure and blood levels of cyclic GMP, free fatty acid, cyclic AMP, glucose and lactic acid were measured in order to evaluate efficacy and dosage of Formoterol and to compare efficacy of this drug with that of Salbutamol."( Evaluation of a new bronchodilator, Formoterol, using biochemical parameters.
Ikuta, T; Inamizu, T; Nishimoto, Y; Onari, K; Tanabe, M; Yamakido, M, 1985
)
" HA-1004 shifted the dose-response curve for CaCl2 to the right in a competitive manner in depolarized rabbit renal arterial strips."( Relaxation of vascular smooth muscle by HA-1004, an inhibitor of cyclic nucleotide-dependent protein kinase.
Hidaka, H; Inagaki, M; Ishikawa, T; Watanabe, M, 1985
)
" This effect proved to be receptor-mediated because preincubation with 10(-5)M atropine shifted the dose-response curve one order of magnitude rightward."( Intact human lymphocyte membranes respond to muscarinic receptor stimulation by oxotremorine with marked changes in microviscosity and an increase in cyclic GMP.
Consolo, S; Ladinsky, H; Masturzo, P; Nordstrom, O; Salmona, M, 1985
)
"Various dosing strategies to determine therapeutic effects of nitroglycerin (NTG) preparations are reviewed."( Hemodynamic attenuation and the nitrate-free interval: alternative dosing strategies for transdermal nitroglycerin.
Flaherty, JT, 1985
)
" The ACTH dose-response curves for steroidogenic activity and for polyamine uptake were similar."( Hormonal control of polyamine levels in bovine adrenocortical cells.
Chambaz, EM; Feige, JJ; Madani, C, 1986
)
" The guanylate cyclase inhibitor methylene blue (10 microM), on the other hand, shifted the dose-response curves for renin release and cGMP levels to 100-fold higher concentrations of ANP."( Atrial natriuretic peptide inhibits renin release from juxtaglomerular cells by a cGMP-mediated process.
Bauer, C; Della Bruna, R; Kurtz, A; Pfeilschifter, J; Taugner, R, 1986
)
" Dose-response studies indicate the beta-adrenergic component of cyclic AMP stimulation is enhanced and the alpha 1-adrenergic component of cyclic GMP stimulation is diminished in LL pinealocytes."( See-saw signal processing in pinealocytes involves reciprocal changes in the alpha 1-adrenergic component of the cyclic GMP response and the beta-adrenergic component of the cyclic AMP response.
Klein, DC; Sugden, D; Vanecek, J; Weller, JL, 1986
)
" To determine if acidic amino acid pathways were involved in this elevation, a low dosage of a selective NMDA antagonist, 2-amino-7-phosphonoheptanoic acid (APH) was injected intracerebroventricularly 4 min before having rats swim 4 laps."( 2-Amino-7-phosphonoheptanoic acid, a selective N-methyl-D-aspartate antagonist, blocks swim-induced elevation of cerebellar cyclic guanosine monophosphate.
McCaslin, PP; Morgan, WW, 1986
)
" Dose-response studies were performed with increasing concentrations of histamine both in the absence and presence of H1 receptor blockade using 10(-5) M diphenhydramine."( Temporal relationship of cyclic nucleotide levels and calcium exchange to histamine-induced tension development.
Kolbeck, RC; Speir, WA, 1984
)
" Dose-response curve analysis revealed a marked hypersensitivity to serotonin as indicated by greater pD2 values (negative logarithm of half maximum dose) than seen in the controls."( Contractions in normal and atherosclerotic rabbit aortas.
Kishi, Y; Numano, F, 1984
)
" Dose-response relationships revealed that more than half-maximal stimulation of guanylate cyclase activity was seen at a concentration as low as 10 nM and nonstimulation of guanylate cyclase activity was seen when the concentration was decreased to 1 nM."( Human and rat growth hormones enhance guanylate cyclase activity.
Vesely, DL, 1981
)
" The dose-response characteristics were similar to those previously described for the inhibition of cAMP accumulation and PTH release by this agent."( Sodium nitroprusside inhibition of parathyroid hormone release is not mediated through cyclic GMP.
Aurbach, GD; Brown, EM; Gardner, DG, 1981
)
"Pretreatment of rats with the beta-adrenergic blocking agents, atenolol, practolol, pronethalol and propranolol, at a dosage of 150 mg/kg/day for 5 days, produced marked increases in guanylate cyclase activity in the liver, gastric and intestinal mucosae, but with concomitant decreases in cyclic GMP levels."( Effect of some beta-adrenergic blocking agents on tissue guanylate cyclase and cyclic nucleotides in the rat.
Ioannides, C; Okine, LK; Parke, DV, 1983
)
" The dose-response relationship for a cholinergic agonist, carbamylcholine, or an adrenergic agonist, norepinephrine, was unaffected by the presence of either 8-Br-cGMP or Bt2cGMP in the medium."( Evidence against a role for guanosine 3',5'-cyclic monophosphate in rat submandibular salivary gland potassium release.
Barzen, KA; Lafferty, JL; Quissell, DO, 1983
)
" Also, the degree of phosphorylation of these specific proteins followed a dose-response relationship with ACTH which correlated well to the dose-response for corticosterone production."( On the mechanism of action of adrenocorticotropic hormone. The role of ACTH-stimulated phosphorylation and dephosphorylation of adrenal proteins.
Gallant, S; Koroscil, TM, 1980
)
" The degree of changes was shown to depend on acetylcholine dosage and animals' age."( [Effect of acetylcholine on cyclic guanosine monophosphate levels in the hearts of rats of different ages].
Kul'chitskiĭ, OK, 1980
)
" Dose-response curves for glycosylation in response to 8-Br-cAMP and GnRH were parallel."( Differential effects of cyclic nucleotide analogues and GnRH on LH synthesis and release.
Jackson, GL; Liu, TC, 1981
)
" 3) The administration of ritodrine and terbutaline at the last trimester of pregnancy led to the increased, showing dose-response relationship, in the heart rate of mother and fetus in rabbits."( [beta 1, beta 2-effects of ritodrine in pregnant animal experiments (author's transl)].
Chimura, T; Inoue, K, 1981
)
"To investigate the mechanism of intracellular transmission of three representative stimuli for gastric acid secretion, the dose-response relations of cyclic nucleotides accompanied by acid secretion stimulated by histamine, pentagastrin and bethanechol were comparatively studied using an in vitro preparation of guinea pig gastric mucosa surviving with a constant potential difference and acid secretion sensitive to amytal."( Cyclic nucleotide response to acid-secreting stimuli in guinea pig gastric mucosa in vitro.
Matsumoto, H; Miyoshi, A; Ohe, K; Shirakawa, T, 1981
)
" 3) The action of c-AMP related substances on the circulatory systems was manifested as the dose-response of beta 1 action to the maternal blood pressure, maternal and fetal heart rate."( [Beta 1-, beta 2-effects of ritrodine and terbutaline in the treatment of preterm labor (author's transl)].
Chimura, T; Inoue, K; Mitsui, T, 1981
)
" It also produced a decrease in 8-Br-cGMP mediated inhibition which was more pronounced when the dosage of LH was increased to 10 microgram/ml."( Inhibitory action of cyclic guanosine 5'-phosphoric acid (GMP) on oocyte maturation: dependence on an intact cumulus.
Hubbard, CJ; Terranova, PF, 1982
)
" The action of AcCho is cooperative, three transmitter-receptor complexes being required to cause a membrane conductance change, and the dose-response curve in most cases can be fitted by an equation assuming the existence of two binding sites with an affinity ratio of about 11."( Cyclic GMP mimics the muscarinic response in Xenopus oocytes: identity of ionic mechanisms.
Dascal, N; Landau, EM, 1982
)
" Reasonably good temporal and dose-response correlations between cyclic GMP elevation and relaxation were obtained with acetylcholine."( Possible role for cyclic GMP in endothelium-dependent relaxation of rabbit aorta by acetylcholine. Comparison with nitroglycerin.
Chu, EB; Diamond, J, 1983
)
" Furthermore, the stimulatory effect was found to be Con A dosage dependent."( Physiological responses of Bacillus species to concanavalin A. 2. Effect on growth, oxygen uptake, enzyme activities and intracellular cyclic guanosine 3',5'-monophosphate level of B. cereus ATCC 14579.
Chan, KY; Lau, TM, 1984
)
" Calmodulin shifted to the right the dose-response relation for activation of the channels by 8-Br-cGMP, but did not change the maximum current or the form of the relation."( Modulation of the cGMP-gated ion channel in frog rods by calmodulin and an endogenous inhibitory factor.
Downing-Park, J; Gordon, SE; Zimmerman, AL, 1995
)
" Inhibitors of phospholipase C, protein kinase C, calcium/calmodulin, nitric oxide synthase and guanylate cyclase activities, shifted to the right the dose-response curve of carbachol upon contractility."( Negative inotropic effect of carbachol on rat atria mediated by nitric oxide.
Genaro, AM; Sterin-Borda, L; Vila Echague, A, 1994
)
" This inhibition reflects the ability of GnRH to shift the CNP dose-response curve rightward (increasing the EC50 for CNP action approximately 10-fold both with and without 3-isobutyl-1-methylxanthine)."( Cyclic guanosine monophosphate production in the pituitary: stimulation by C-type natriuretic peptide and inhibition by gonadotropin-releasing hormone in alpha T3-1 cells.
Käppler, K; McArdle, CA; Poch, A, 1993
)
" Nitroprusside, atriopeptin II and 8-Br-cGMP all increased renin release but the dose-response relationships were biphasic."( Cyclic GMP-linked pathway for renin secretion.
Abu-Kishk, RA; D'Aloia, MA; Lush, DJ; Noble, AR; Williams, BC, 1994
)
"Hypertonic-iso/hyperoncotic solutions have been the subject of numerous studies, mostly used in a fixed dosage (4 mL/kg bw or 250 mL)."( Optimal preoperative titrated dosage of hypertonic-hyperoncotic solutions in cardiac risk patients.
Albrecht, DM; Ellinger, K; Fähnle, M; Schroth, M, 1995
)
" Dose-response curves were generated to each contractile agonist."( Pulmonary hypertension in acute lung injury is due to impaired vasodilation with intact vascular contractility.
Agrafojo, J; Banerjee, A; Fullerton, DA; McIntyre, RC, 1995
)
" The dose-response relation for on-bipolar cells showed no gradual saturation, but increased linearly with a sharp cutoff above 200 microM glutamate."( Responses of rod bipolar cells isolated from dogfish retinal slices to concentration-jumps of glutamate.
Falk, G; Shiells, RA,
)
" Prior exposure to lead produced a dose-response inhibition of retinal cGMP-phosphodiesterase (PDE) resulting in an increase in cGMP in dark-adapted and light-adapted states and an increase in the calcium content of rods."( Lead-induced alterations in rod-mediated visual functions and cGMP metabolism: new insights.
Fox, DA; Hurwitz, RL; Srivastava, D, 1994
)
" Sodium nitroprusside was infused intracoronarily at a dosage (< or = 4 micrograms/min) that was previously shown to be devoid of systemic effects when infused into the brachial artery to investigate the reactivity of the forearm vascular bed."( Acute effects of nitric oxide on left ventricular relaxation and diastolic distensibility in humans. Assessment by bicoronary sodium nitroprusside infusion.
Paulus, WJ; Shah, AM; Vantrimpont, PJ, 1994
)
" Dose-response curves for sodium nitroprusside, nitroglycerin, isoproterenol, amrinone, and PGE1 were then generated."( Pulmonary vascular smooth muscle relaxation by cGMP- versus cAMP-mediated mechanisms.
Banerjee, A; Fullerton, DA; Hahn, AR; Harken, AH, 1994
)
" Dose-response curves for net fluid secretion (stimulated-basal (30 min)-1) activated by 5,50 and 500 ng ml-1 STa were obtained for jejuna and ilea from fed, starved and chronically undernourished rats."( Fluid hypersecretion induced by enterotoxin STa in nutritionally deprived rats: jejunal and ileal dynamics in vivo.
Levin, RJ; Nzegwu, HC, 1994
)
" Six-minute pretreatment with 50 nmol of the nitric oxide synthase inhibitor L-NG-nitroarginine (NNR) significantly inhibited CD-produced hot-plate and tail-flick antinociception as evidenced by 6-fold shifts to the right of the CD dose-response curves."( Pharmacologic evidence that spinal muscarinic analgesia is mediated by an L-arginine/nitric oxide/cyclic GMP cascade in rats.
Iwamoto, ET; Marion, L, 1994
)
" A strong correlation between phosphate incorporation into guanylate cyclase and increased cGMP level was also observed by time-course and dose-response studies of the PMA effect, as well as when cells were treated with various phorbol esters and diacylglycerols or with various protein kinase C inhibitors."( Activation of soluble guanylate cyclase through phosphorylation by protein kinase C in intact PC12 cells.
Louis, JC; Revel, MO; Zwiller, J, 1993
)
" Cyclic GMP dose-response curves to CNP failed to show any signs of saturation even at concentrations up to 30 microM, indicating a relatively low affinity of CNP for the GC-B receptor."( Characterization of natriuretic peptide receptor subtypes in the AtT-20 pituitary tumour cell line.
Cramb, G; Gilkes, AF; Guild, SB; Ogden, PH, 1994
)
" Drugs were dosed as dry powders directly into the tracheobronchial tree and MVL was assessed by using the fluorescent macromolecule fluorescein isothiocyanate-dextran (FITC-dextran, 150 kD)."( Effects of isoenzyme-selective inhibitors of cyclic nucleotide phosphodiesterase on microvascular leak in guinea pig airways in vivo.
Karlsson, JA; Raeburn, D, 1993
)
" We found that the cyclic AMP-induced cytoskeletal actin response was similar to that of the parental strain in this mutant (although showing a slight displacement in the dose-response curve) but the cytoskeletal myosin II heavy chain response was abolished."( The role of cyclic GMP in regulating myosin during chemotaxis of Dictyostelium: evidence from a mutant lacking the normal cyclic GMP response to cyclic AMP.
Ishida, S; Kuwayama, H; Liu, G; Newell, PC, 1993
)
" The differences between aorto-caval fistula rats and sham operated rats were probably the result of increased basal EDRF-NO release in the former, since NO synthase blockade abolished the differences in both aortic cGMP and the dose-response curve to Sin-1."( Vascular relaxation and cyclic guanosine monophosphate in a rat model of high output heart failure.
Arnal, JF; Michel, JB; Schott, C; Stoclet, JC, 1993
)
" Nuclear extracts of stimulated cells show increased binding capacity to the AP1 binding site consistent with the dose-response curve."( Stimulation of the cyclic GMP pathway by NO induces expression of the immediate early genes c-fos and junB in PC12 cells.
Aunis, D; Haby, C; Lisovoski, F; Zwiller, J, 1994
)
"The effects of human atrial natriuretic peptide (ANP) on glomerular filtration rate (GFR), renal plasma flow (RPF), urinary flow rate, urinary sodium excretion, tubular function estimated by lithium clearance, and plasma levels of sodium and water homeostatic hormones were studied in a dose-response study with 50 healthy subjects."( Dose-response study of atrial natriuretic peptide bolus injection in healthy man.
Eiskjaer, H; Pedersen, EB, 1993
)
" Dose-response curves for the two peptides were superimposable in each tissue; at 10(-6) M, ANP generated 613 +/- 41 and urodilatin 603 +/- 55 fmol cyclic guanosine monophosphate per 10 minutes per milligram protein in inner medullary collecting duct cells (p = NS)."( Urodilatin binds to and activates renal receptors for atrial natriuretic peptide.
Humphreys, MH; Qui, C; Schambelan, M; Sechi, LA; Valentin, JP, 1993
)
" The dose-response relationship for the IP3 response of L-Cys and L-Ala in the range from 10 nM to 1 mM is consistent with previous electrophysiological and ligand binding experiments."( Rapid kinetic measurements of second messenger formation in olfactory cilia from channel catfish.
Boekhoff, I; Breer, H; Restrepo, D, 1993
)
" In treated TASM, washed free of AP III, acute dose-response curves of cGMP to AP III were not different from that in untreated cells."( Regulation of atrial natriuretic peptide receptors in vascular smooth muscle cells: role of cGMP.
Newman, WH; Tao, H; Zhang, LM, 1993
)
"1-10 mumol/kg) produced a bell-shaped dose-response curve for the secretory rate, bicarbonate and protein outputs."( Effects of peptide histidine isoleucine on pancreatic exocrine secretion in anaesthetized dogs.
Chiba, S; Iwatsuki, K; Ren, LM,
)
" Inhibitors of phospholipase C, protein kinase C, calcium/calmodulin, nitric oxide synthase and guanylate cyclase, shifted the dose-response curve of carbachol on contractility to the right."( Endogenous nitric oxide signalling system and the cardiac muscarinic acetylcholine receptor-inotropic response.
Borda, E; Echagüe, AV; Genaro, A; Leiros, CP; Sterin-Borda, L, 1995
)
" Dose-response curves to ACh, A23187, and SNP were generated in isolated pulmonary artery rings preconstricted with phenylepherine."( Antibody-mediated neutrophil depletion preserves pulmonary vasomotor function.
Agrafojo, J; Cleveland, JC; Eisenach, JH; Fullerton, DA; Harken, AH; McIntyre, RC; Meldrum, DR; Sheridan, BC, 1996
)
" In the presence of PD 123319 (10(-5) M) ANG dose-response curve was shifted to the left with no change in the maximal effect."( Angiotensin II receptor subtypes and phosphoinositide hydrolysis in rat adrenal medulla.
Garrido, MR; Israel, A; Saavedra, JM; Strömberg, C; Torres, M; Tsutsumi, K, 1995
)
" Glibenclamide (30 microM) had no significant effect on relaxation of the dose-response curve to nitroglycerin and almost completely abolished the relaxation by cromakalim, a known opener of ATP-sensitive potassium channels."( Effect of selective inhibition of potassium channels on vasorelaxing response to cromakalim, nitroglycerin and nitric oxide of canine coronary arteries.
Hohn, J; Papp, JG; Pataricza, J; Penke, B; Toth, GK, 1995
)
" The dose-response relations were much shallower than predicted by single-site activation models, but were well described by models in which there are two populations of sites, in roughly equal proportion, that bind cGMP with apparent affinities that differ by a factor of 25."( Covalent activation of retinal rod cGMP-gated channels reveals a functional heterogeneity in the ligand binding sites.
Brown, RL; Karpen, JW, 1996
)
" In permeabilized hepatocytes, the dose-response curve for InsP3-induced Ca2+ release was shifted to the left in the presence of 8-Br-cGMP."( 3':5'-cyclic guanosine monophosphate (cGMP) potentiates the inositol 1,4,5-trisphosphate-evoked Ca2+ release in guinea-pig hepatocytes.
Capiod, T; Combettes, L; Guihard, G, 1996
)
" The dose-response curve for activation of the cGMP-gated channel had a half-maximal value of 36."( Cyclic GMP-gated channels of bovine rod photoreceptors: affinity, density and stoichiometry of Ca(2+)-calmodulin binding sites.
Bauer, PJ, 1996
)
" The dose-response curve for cGMP at CNG channels is used as a calibration to provide a quantitative estimate of the CO-stimulated cGMP formation."( Regulation of cyclic nucleotide-gated channels and membrane excitability in olfactory receptor cells by carbon monoxide.
Leinders-Zufall, T; Shepherd, GM; Zufall, F, 1995
)
" Dose-response curves for tetracaine in the presence of saturating cGMP are well fit with a Michaelis-Menten binding scheme indicating that a single tetracaine molecule is sufficient to produce block."( Mechanism of tetracaine block of cyclic nucleotide-gated channels.
Fodor, AA; Gordon, SE; Zagotta, WN, 1997
)
" Dose-response curves to acetylcholine and sodium nitroprusside were generated in isolated pulmonary artery rings preconstricted with phenylephrine (n = 10 rings/5 rats per group)."( Neutrophils mediate pulmonary vasomotor dysfunction in endotoxin-induced acute lung injury.
Agrafojo, J; Fullerton, DA; McIntyre, RC; Meldrum, DR; Moore, EE; Sheridan, BC, 1997
)
" In thoracic aortic strips with intact endothelium, the first and second (1 h later) dose-response curves obtained with methoxamine were almost the same."( A comparative study on the rat aorta and mesenteric arterial bed of the possible role of nitric oxide in the desensitization of the vasoconstrictor response to an alpha 1-adrenoceptor agonist.
Kamata, K; Makino, A, 1997
)
" It was reported to potentiate GABA-mediated chloride current in cultured cells with a moderate intrinsic activity and a biphasic dose-response relationship."( Anxiolytic-like effects of PNU-101017, a partial agonist at the benzodiazepine receptor.
Carter, DB; Franklin, SR; Jacobsen, EJ; Needham, LM; Sethy, VH; Tang, AH; Von Voigtlander, PF, 1997
)
" In vivo, V-PYRRO/NO increased liver cGMP levels while minimally affecting systemic hemodynamics, protecting rats dosed with TNF alpha plus galactosamine from apoptosis and hepatotoxicity."( Targeting nitric oxide (NO) delivery in vivo. Design of a liver-selective NO donor prodrug that blocks tumor necrosis factor-alpha-induced apoptosis and toxicity in the liver.
Billiar, TR; Keefer, LK; Kim, YM; Saavedra, JE; Watkins, SC; Williams, DL, 1997
)
" The time course and dose-response pattern of this effect remain to be elucidated."( Dose-related effect of intravenous L-arginine on muscular blood flow of the calf in patients with peripheral vascular disease: a H215O positron emission tomography study.
Alexander, K; Bode-Böger, SM; Böger, RH; Burchert, W; Frölich, JC; Galland, A; Hundeshagen, H; Schellong, SM, 1997
)
" Dose-response curves for platelet aggregation by collagen were constructed both in the absence and presence of 2 microM SIN-1, an NO donor, to quantify the antiaggregation effects of NO."( Acute vigorous exercise attenuates sensitivity of platelets to nitric oxide.
Kishi, Y; Numano, F; Sakita, S, 1997
)
" The antagonists' order of potency to displace dose-response curve of CARB was: ATROP > 4-DAMP > AF-DX116 > PZ."( Intracellular signals coupled to different rat ileal muscarinic receptor subtypes.
Borda, ES; Rodriguez, M; Sales, ME; Sterin-Borda, L, 1997
)
" doses of morphine, as demonstrated by a 120-fold rightward shift of the morphine dose-response curve."( The nitric oxide/cyclic GMP system at the supraspinal site is involved in the development of acute morphine antinociceptive tolerance.
Bidlack, JM; Hill, KP; Xu, JY, 1998
)
" Nicorandil (3 mg/kg) given orally was rapidly absorbed, reaching the maximal plasma (approximately 2,600 ng/ml) and vascular concentrations (approximately 176 ng/g) at 15 min after the dosing and thereafter decreased rapidly."( Vascular levels and cGMP-increasing effects of nicorandil administered orally to rats.
Akima, M; Kamachi, S; Kitajima, S; Moriyasu, M; Sakai, K; Tanikawa, M, 1998
)
" S-nitroso-N-acetylpenicillamine (SNAP) also raised cGMP concentrations with similar dose-response relations."( Inhibition of proximal tubular fluid absorption by nitric oxide and atrial natriuretic peptide in rat kidney.
Eitle, E; Harris, PJ; Hiranyachattada, S; Wang, H, 1998
)
" Inhibition of NOS and guanylate cyclase increased the dose-response curve of isoproterenol on contractility."( Role of nitric oxide in cardiac beta-adrenoceptor-inotropic response.
Borda, E; Cremaschi, G; Genaro, A; Perez Leiros, C; Sterin-Borda, L; Vila Echagüe, A, 1998
)
" There was a U-shaped dose-response curve and LHRH release was not inhibited at lower or higher cytokine concentrations."( Granulocyte-macrophage colony stimulating factor suppresses LHRH release by inhibition of nitric oxide synthase and stimulation of gamma-aminobutyric acid release.
Kimura, M; McCann, SM; Rettori, V; Yu, WH,
)
" However, the inhibition of the combined CPA and CCh response was reduced and the dose-response curve of SIN-1 shifted to the right."( Involvement of intracellular Ca2+ stores in inhibitory effects of NO donor SIN-1 and cGMP.
Allescher, HD; Franck, H; Puschmann, A; Schusdziarra, V; Storr, M, 1998
)
" After MTSET treatment, the dose-response relation for cGMP was shifted by over two orders of magnitude to lower concentrations."( Movement of gating machinery during the activation of rod cyclic nucleotide-gated channels.
Brown, RL; Haley, TL; Snow, SD, 1998
)
" Drugs or vehicle (V) were administered subcutaneously for 6 weeks with dosing initiated 1 week after renal mass reduction."( Protective effects of CGS 30440, a combined angiotensin-converting enzyme inhibitor and neutral endopeptidase inhibitor, in a model of chronic renal failure.
Cohen, DS; Dotson, RA; Graybill, SR; Mathis, JE; Wosu, NJ, 1998
)
" Synergism might also lead to a reduction in dosage and a decreased risk of side-effects."( Rationale for the combination of anti-aggregating drugs.
Herman, AG, 1998
)
" Uniquely, a number of these analogues were found to have a bell-shaped dose-response profile in the alpha1 beta2 gamma2 subtype as determined by whole cell patch-clamp technique, where in vitro efficacy was found to decrease with increasing drug concentration."( Piperazine imidazo[1,5-a]quinoxaline ureas as high-affinity GABAA ligands of dual functionality.
Belonga, KL; Carter, DB; Im, HK; Im, WB; Jacobsen, EJ; Mickelson, JW; Petke, JD; Sethy, VH; Stelzer, LS; Tang, AH; TenBrink, RE; VonVoigtlander, PF; Zhong, WZ, 1999
)
" Glutamate treatment caused a dose-response increase of cyclic GMP levels in hippocampal slices."( Glutamate release is involved in PAF-increased cyclic GMP levels in hippocampus.
Calcerrada, MC; Catalán, RE; Martínez, AM, 1999
)
" Dose-response curves for glutamate (0-1 mM) and kainate (0-200 microM) were measured in the presence and absence of 1-2 mM sodium nitroprusside (SNP), 1 mM 8-Br-cGMP, 100 microM cyclothiazide or 200 microM dopamine as modulators."( Horizontal cell glutamate receptor modulation by NO: mechanisms and functional implications for the first visual synapse.
McMahon, DG; Schmidt, KF,
)
" The dose-response for SNAP increases in cyclic GMP was shifted nearly two orders of magnitude lower in the presence of glutathione."( Comparative effects of several nitric oxide donors on intracellular cyclic GMP levels in bovine chromaffin cells: correlation with nitric oxide production.
Ferrero, R; Miras-Portugal, MT; Rodríguez-Pascual, F; Torres, M, 1999
)
" Comparative dose-response curves indicated that maximal hormone-stimulated cAMP accumulation was 11- and 24-fold higher in human and rat cells, compared with cAMP production obtained in corresponding membranes, respectively."( Comparative involvement of cyclic nucleotide phosphodiesterases and adenylyl cyclase on adrenocorticotropin-induced increase of cyclic adenosine monophosphate in rat and human glomerulosa cells.
Côté, M; Gallo-Payet, N; Guillon, G; Payet, MD; Rousseau, E, 1999
)
" The dose-response relation for activation is usually fit with the Hill equation, I/I(max) = [cGMP]n/([cGMP]n + K(1/2)n, where I/I(max) is the fraction of maximal current, K(1/2) is the concentration of cGMP that gives a half-maximal current, and n is the Hill coefficient, taken as the minimum number of ligands required for significant activation."( The single-channel dose-response relation is consistently steep for rod cyclic nucleotide-gated channels: implications for the interpretation of macroscopic dose-response relations.
Brown, RL; Haley, TL; He, Y; Karpen, JW; Ruiz, M, 1999
)
" The dose-response relation at -100 mV was shifted to the right and saturated at significantly lower P(o) values with respect to that at +100 mV (0."( Gating by cyclic GMP and voltage in the alpha subunit of the cyclic GMP-gated channel from rod photoreceptors.
Benndorf, K; Eismann, E; Kaupp, UB; Koopmann, R, 1999
)
" Force of contraction was measured during dose-response testing of combinations of L-arginine and amrinone, milrinone, zaprinast, or sildenafil."( Interaction of L-arginine and phosphodiesterase inhibitors in vasodilation of the porcine internal mammary artery.
Tom, WL; Wallace, AW, 2000
)
" At high (>300 mmHg) vs low (<55 mmHg) oxygen tension the dose-response curves to NO- and SNP-induced relaxations were biphasic and shifted leftward."( Nitric oxide and sodium nitroprusside-induced relaxation of the human umbilical artery.
Lovren, F; Triggle, C, 2000
)
" Plasma atrial and brain natriuretic peptide and cGMP levels were stable acutely (P=NS), while brain natriuretic peptide increased after repeated dosing in severe HF (P<0."( Beneficial renal and hemodynamic effects of omapatrilat in mild and severe heart failure.
Espiner, EA; Frampton, CM; Nicholls, MG; Powell, JD; Rademaker, MT; Richards, AM; Troughton, RW; Yandle, TG, 2000
)
" In chronically instrumented dogs, sildenafil (2 mg/kg per os) augmented the vasodilator response to acetylcholine, with a leftward shift of the dose-response curve relating coronary flow to acetylcholine dose."( Effect of sildenafil on coronary active and reactive hyperemia.
Bache, RJ; Chen, Y; Du, R; Traverse, JH, 2000
)
" This dose of ZD2574 markedly blunted the pressor response to ET-1, indicating effective blockade of ET(A) receptors, and also abolished the initial transient depressor response to ET-1, indicating that blockade of endothelial ET(B) receptors also occurred using this dosage regimen for ZD2574."( Endothelin receptor antagonism does not prevent the development of in vivo glyceryl trinitrate tolerance in the rat.
Adams, MA; Bennett, BM; Fraser, AB; Ratz, JD; Rees-Milton, KJ, 2000
)
" Using an ex vivo model of coronary perfusion in rabbits, we found a dose-response relationship between VEGF and the efficiency of adenoviral gene transfer."( Phosphodiesterase inhibitor-mediated potentiation of adenovirus delivery to myocardium.
Donahue, JK; Lawrence, JH; Marbán, E; Nagata, K, 2001
)
" Wild-type mice dosed orally with the drug (25 mg."( Sildenafil inhibits hypoxia-induced pulmonary hypertension.
Aldashev, A; Kojonazarov, B; Maripov, A; Mason, NA; Mirrakhimov, MM; Morrell, NW; Sadykov, A; Wilkins, MR; Zhao, L, 2001
)
" These properties have served to suggest YC-1 as an attractive therapeutic agent by permitting the reduction of nitrovasodilator dosage and regulating endogenous cGMP metabolism."( Prolonged exposure to YC-1 induces apoptosis in adrenomedullary endothelial and chromaffin cells through a cGMP-independent mechanism.
Ferrero, R; Torres, M, 2001
)
" Inhibitors of phospholipase C (PLC), protein kinase C (PKC), calcium/calmodulin, NOS and guanylate cyclase shifted the dose-response curve of CPA on contractility to the right."( Role of nitric oxide/cyclic GMP in myocardial adenosine A1 receptor-inotropic response.
Borda, E; Gómez, RM; Sterin-Borda, L, 2002
)
" We then investigated antagonism between second messengers: dose-response curves were constructed for stimulation of Tenebrio molitor tubules by cyclic AMP and their inhibition by cyclic GMP."( Antagonistic control of fluid secretion by the Malpighian tubules of Tenebrio molitor: effects of diuretic and antidiuretic peptides and their second messengers.
Eigenheer, RA; Nicolson, SW; Schooley, DA; Wiehart, UI, 2002
)
"We studied the dose-response effects of acute administration of the selective A1 adenosine receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA), the selective A2A agonists 2-hexynyl-5'-N-ethylcarboxamidoadenosine (2HE-NECA) and 2-[4-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamidoadenosine (CGS 21680) and the non-selective agonist N-ethylcarboxamidoadenosine (NECA) on plasma renin activity, atrial natriuretic peptide, cyclic guanosine 3',5'-monophosphate (cGMP) and endothelin-1 in spontaneously hypertensive rats."( Humoral effects of selective adenosine agonists in spontaneously hypertensive rats.
Alberti, C; Casati, C; Monopoli, A; Morganti, A; Ongini, E; Sala, C; Zanchetti, A, 1996
)
" Both humoral and hemodynamic parameters were determined 1 h after dosing in separate sets of animals."( Humoral effects of selective adenosine agonists in spontaneously hypertensive rats.
Alberti, C; Casati, C; Monopoli, A; Morganti, A; Ongini, E; Sala, C; Zanchetti, A, 1996
)
" Baseline tone, electrical field stimulation (EFS)-induced nitric oxide-mediated off responses, and changes in the cholecystokinin (CCK)-8 dose-response relationship were measured."( The effect of phosphodiesterase inhibition on gallbladder motility in vitro.
Conklin, JL; Cullen, JJ; Hinkhouse, MM; Lindaman, BA, 2002
)
" Caffeine (10(-5) M) and EHNA increased the CCK-8 dose-response contractions."( The effect of phosphodiesterase inhibition on gallbladder motility in vitro.
Conklin, JL; Cullen, JJ; Hinkhouse, MM; Lindaman, BA, 2002
)
" SNAC reduced the medium arterial pressure in a dose-response manner in both normotensive and hypertensive animals."( Characterization of the hypotensive effect of S-nitroso-N-acetylcysteine in normotensive and hypertensive conscious rats.
de Oliveira, MG; Krieger, MH; Ricardo, KF; Shishido, SM, 2002
)
"A biphasic dose-response curve emerged for both the neutrophil spontaneous random migration and the fMLP-induced chemotaxis."( Hemin, a heme oxygenase substrate analog, both inhibits and enhances neutrophil random migration and chemotaxis.
Andersson, JA; Cardell, LO; Uddman, R, 2002
)
" Addition of SNP potentiated the relaxation effect of YC-1 and A-350619, shifting the dose-response curve to the left to 3 microM and 10 microM, respectively."( A-350619: a novel activator of soluble guanylyl cyclase.
Brioni, JD; Chang, R; Hsieh, GC; Kolasa, T; Miller, LN; Moreland, RB; Nakane, M, 2003
)
" A dose-response study of GLP-1 with glucose-stimulated islets showed that GLP-1 could overcome and completely restore the impaired insulin release in TPN islets, bringing about a marked increase in islet cAMP accumulation concomitant with heavy suppression of both glucose-stimulated increase in islet cGMP content and the activities of constitutive NOS (cNOS) and iNOS."( Total parenteral nutrition-stimulated activity of inducible nitric oxide synthase in rat pancreatic islets is suppressed by glucagon-like peptide-1.
Ekelund, M; Lundquist, I; Salehi, A, 2003
)
" 5 Gy in a dose-dependent manner, thus giving rise to J-shaped dose-response curves."( Involvement of the Ca(2+)-protein kinase C and adenyilate cyclace signal pathways in the activation of thymocytes in response to whole-body irradiation with low dose X-rays.
Liu, S; Xie, F, 2000
)
" As scheduled sexual activities are not preferred by the majority of couples, the future of ED-therapy will focus on drugs with a 1-2 day long efficacy window, or a daily bedtime application of low dosage agents which result in nocturnal reoxygenation of the cavernous bodies and in turn in functional improvement."( [Therapy of erectile dysfunction in 2005].
Porst, H, 2003
)
" Inhibition by ATR was not voltage dependent, and the form of its dose-response relation suggested multiple ATR molecules interacting per channel."( All-trans-retinal is a closed-state inhibitor of rod cyclic nucleotide-gated ion channels.
Kovithvathanaphong, P; Mahajan, R; McCabe, SL; Miri, A; Nguitragool, W; Pelosi, DM; Tetreault, M; Zimmerman, AL, 2004
)
" A plot of peritubular cGMP concentration vs Vbl revealed a steep dose-response between 300 micromol l(-1) and 700 micromol l(-1) with an EC50 of 468 micromol l(-1)."( The mechanism of action of the antidiuretic peptide Tenmo ADFa in Malpighian tubules of Aedes aegypti.
Beyenbach, KW; Lee, LW; Massaro, RC; Patel, AB; Schegg, KM; Schooley, DA; Scott, BN; Wu, DS; Yu, MJ, 2004
)
" In control (missense ODN treated) rats, forskolin elicited a leftward shift in the SNAP dose-response curves (approximately 50% reduction in SNAP EC50)."( cAMP modulates cGMP-mediated cerebral arteriolar relaxation in vivo.
Baughman, VL; Gavrilyuk, V; Pelligrino, DA; Wolde, HM; Xu, HL, 2004
)
" We relate this effect to the high cholesterol content of DRMs because manipulating the cholesterol content of rod outer segment membranes by methyl-beta-cyclodextrin yielded a similar shift of the Ca2+-dependent dose-response curve of rhodopsin kinase inhibition."( Recoverin and rhodopsin kinase activity in detergent-resistant membrane rafts from rod outer segments.
Churumova, VA; Höppner-Heitmann, D; Koch, KW; Philippov, PP; Polkovnikova, OO; Senin, II; Tikhomirova, NK, 2004
)
" In the present study, comparison of dose-response relations for hyperalgesia produced by PGE2, forskolin, 8-Br-cAMP, or the protein kinase A (PKA) catalytic subunit, in primed versus normal animals, demonstrated that priming-induced enhancement of the PGE2-activated second messenger cascade occurs downstream to adenylate cyclase and upstream to PKA."( Chronic hyperalgesic priming in the rat involves a novel interaction between cAMP and PKCepsilon second messenger pathways.
Levine, JD; Parada, CA; Reichling, DB, 2005
)
" Methylene blue (MB) but not N(omega)-nitro-L-arginine methylester (L-NAME) or ODQ (1H-[1,2,4]oxadiazol-[4,3-]quinoxsalin-1-one) modified the dose-response curve of ginsenoside Rg(3)."( Relaxation of canine corporal smooth muscle relaxation by ginsenoside saponin Rg3 is independent from eNOS activation.
Chang, KC; Kang, YJ; Sohn, JT, 2005
)
" In both dogfish and eel, AD dose-response curves showed a biphasic effect: vasoconstriction (pico to nanomolar range) and vasodilation (micromolar range)."( Adenosine/nitric oxide crosstalk in the branchial circulation of Squalus acanthias and Anguilla anguilla.
Pellegrino, D; Randall, DJ; Tota, B, 2005
)
" Soluble Cys-NO was used in preliminary studies to identify dosage ranges that were able to simultaneously inhibit smooth muscle cell proliferation, enhance endothelial cell proliferation, and reduce platelet adhesion."( Nitric oxide-generating hydrogels inhibit neointima formation.
Liel, MS; Lipke, EA; Masters, KS; Myler, HA; Rice, EE; Tulis, DA; West, JL; Zygourakis, C, 2005
)
" Overall, a significant dose-response relationship was noted between NO exposure and markers of aging with between 50 and 100 microM SNAP (0."( Nitric oxide delays oocyte aging.
Abu-Soud, HM; Diamond, MP; Goud, AP; Goud, PT, 2005
)
" In the low-salt panel the rise in plasma active renin concentration achieved 24 hours after dosing by 25 mg AVE7688 (247 pg/mL [95% CI, 157-389 pg/mL], P < ."( Pharmacokinetics and pharmacodynamics of the vasopeptidase inhibitor AVE7688 in humans.
Azizi, M; Bissery, A; Floch, A; Guyene, TT; Ménard, J; Ozoux, ML; Peyrard, S, 2006
)
" Conversely, BAY 41-2272, a sGC stimulator, increased I(sc) in a dose-response fashion."( Mechanisms of cystic fibrosis transmembrane conductance regulator activation by S-nitrosoglutathione.
Bosworth, CA; Chen, L; Lancaster, JR; Matalon, S; Patel, RP; Teng, X, 2006
)
" The Ca(2+) dose-response studies demonstrated that cGMP shifted the dose-response curve upward with no shift to the lower concentration."( cGMP modulation of ACh-stimulated exocytosis in guinea pig antral mucous cells.
Fujiwara, S; Katsu, K; Marunaka, Y; Nakahari, T; Saad, AH; Shimamoto, C, 2006
)
" Dose-response curves for carbachol revealed a lower peak response in new-born bladders compared with adults."( Developmental regulation of nerve and receptor mediated contractions of mammalian urinary bladder smooth muscle.
Andersson, KE; Arner, A; Ekman, M, 2006
)
" Treatment-related adverse events were experienced by 43% of the patients administered GW660511X 200 mg and 44% of those dosed with placebo with headache the most commonly reported."( A randomized, double-blind, placebo-controlled, parallel-group study to assess the efficacy and safety of dual ACE/NEP inhibitor GW660511X in mild-to-moderate hypertensive patients.
Danoff, TM; Johnson, AG; Pearce, GL, 2006
)
" In dose-response measures, NO increased the current stimulated by cAMP injection without altering either apparent cAMP binding affinity or cooperativity of current activation."( Nitric oxide potentiates cAMP-gated cation current in feeding neurons of Pleurobranchaea californica independent of cAMP and cGMP signaling pathways.
Gillette, R; Hatcher, NG; Moroz, LL; Sudlow, LC, 2006
)
" Dose-response curves of the probucol groups showed an improvement in endothelium-dependent relaxations, associated with increased nitric oxide bioavailability and decreased angiotensin II and hydroperoxide levels."( Role of probucol on endothelial dysfunction of epicardial coronary arteries associated with left ventricular hypertrophy.
Aubin, MC; Carrier, M; Perrault, LP; Shi, YF; Tardif, JC, 2006
)
" A-778935 relaxed cavernosum tissue strips in a dose-dependent manner; and in the presence of 1 microM SNP, A-778935 relaxed the strips more potently, shifting the dose-response curve to the left."( Acrylamide analog as a novel nitric oxide-independent soluble guanylyl cyclase activator.
Brioni, JD; Chang, R; Kolasa, T; Miller, LN; Moreland, RB; Nakane, M, 2006
)
" Infusion of the NO synthase blocker L-NMMA (100 microM) caused a rightward shift of the dose-response curve of vardenafil."( Vardenafil increases coronary flow response to hypercapnic acidosis in isolated guinea pig heart.
Brand, M; Deussen, A, 2007
)
" In keeping with the SNP dose-response curves, the sGC agonists significantly relaxed the newborn, but not the adult bronchial muscle."( Soluble guanylate cyclase-dependent relaxation is reduced in the adult rat bronchial smooth muscle.
Behrends, S; Belik, J; Hehne, N; Pan, J, 2007
)
" L-DOPA was administered subchronically for 11 days (beginning 3 days after last MPTP/NaCl injection) or for 14 days (with dosing started immediately following the last MPTP/NaCl injection)."( The effect of subchronic, intermittent L-DOPA treatment on neuronal nitric oxide synthase and soluble guanylyl cyclase expression and activity in the striatum and midbrain of normal and MPTP-treated mice.
Chalimoniuk, M; Langfort, J, 2007
)
" Within the 10-100 ng/ml range, porcine relaxin showed the highest effects and a nearly linear dose-response correlation."( A novel, simple bioactivity assay for relaxin based on inhibition of platelet aggregation.
Bani, D; Bigazzi, M; Cinci, L; Elliott, L; Giannini, L; Masini, E; Nistri, S; Princivalle, M, 2007
)
" Dose-response curves were generated to evaluate endothelium-dependent and endothelium-independent vasoreactivity, ex vivo."( A mouse model of hypercholesterolemia-induced erectile dysfunction.
Annex, BH; Donatucci, CF; Odronic, SI; Pippen, AM; Wu, F; Xie, D, 2007
)
" In all patients, diuretics were administered according to a standardized dosing algorithm."( The effects of nesiritide on renal function and diuretic responsiveness in acutely decompensated heart failure patients with renal dysfunction.
Burnett, JC; Chen, HH; Frantz, RP; Hodge, DO; Karon, BL; Miller, WL; Owan, TE; Redfield, MM; Rodeheffer, RJ, 2008
)
" We could show that several mutant channels with agonist dose-response relationships similar to the wild-type exhibited severely impaired membrane targeting."( Mutations in CNGA3 impair trafficking or function of cone cyclic nucleotide-gated channels, resulting in achromatopsia.
Baumann, B; Koeppen, K; Kohl, S; Ladewig, T; Reuter, P; Wissinger, B, 2008
)
"The rats implanted with 9L gliosarcoma were dosed orally with hydroxyurea and L-arginine."( Increase in brain tumor permeability in glioma-bearing rats with nitric oxide donors.
Black, KL; Espinoza, AJ; Hu, J; Irvin, DK; Ko, MK; Konda, BM; Ong, JM; Sacapano, MR; Shu, Y; Wang, X; Yin, D, 2008
)
"5-10 microg) microinjected into the VTA induces penile erection with an inverted U-shaped dose-response curve; the maximal effective dose being 3 microg."( Oxytocin induces penile erection when injected into the ventral tegmental area of male rats: role of nitric oxide and cyclic GMP.
Argiolas, A; Boi, A; Cocco, C; Ferri, GL; Melis, MR; Melis, T; Sanna, F; Succu, S, 2008
)
" The cell-permeable cGMP analog 8-bromo-cGMP produced a dose-dependent relaxation of the uterine artery and shifted norepinephrine (NE) dose-response curve to the right with a decreased maximal contraction."( Effect of cGMP on pharmacomechanical coupling in the uterine artery of near-term pregnant sheep.
Hu, X; Xiao, D; Zhang, L, 2008
)
" Despite increasing numbers of studies using NPs in therapy of acute and chronic CHF, several controversies regarding safety, efficacy, and dosing of NPs need to be addressed."( Insights into natriuretic peptides in heart failure: an update.
Boerrigter, G; Burnett, JC; Korinek, J; Mohammed, SF, 2008
)
"A physical morphine dependent model of rats was established by subcutaneous injection of morphine in gradually increasing dosage within 7 days."( [Effect of cedemex on cAMP and cGMP levels of different brain areas in morphine withdrawal rats].
Chen, TP; Fan, JM; Guo, SC; Huang, JC; Huang, RB; Jiang, WZ; Lai, S; Liang, YG; Nguyen, PK; Xie, HY, 2008
)
"We investigated changes in serum biomarkers of vascular function after short-term, continuous sildenafil dosing in men with type 2 diabetes with erectile dysfunction."( Serum biomarker measurements of endothelial function and oxidative stress after daily dosing of sildenafil in type 2 diabetic men with erectile dysfunction.
Bivalacqua, TJ; Burnett, AL; Jin, L; Musicki, B; Strong, TD; Trock, BJ, 2009
)
" In addition, the dose-response curves of KCl (2."( The vasorelaxant effect of caffeic acid phenethyl ester on porcine coronary artery ring segments.
Chen, J; Chen, Q; Han, M; Long, Y; Tian, XZ; Wang, R,
)
" Interestingly, at higher doses, R(max) to acetylcholine was attenuated leading to U-shaped dose-response curves."( Dose-dependent effects of a selective phosphodiesterase-5-inhibitor on endothelial dysfunction induced by peroxynitrite in rat aorta.
Arif, R; Barnucz, E; Hirschberg, K; Karck, M; Korkmaz, S; Loganathan, S; Neugebauer, P; Radovits, T; Seidel, B; Szabó, G, 2009
)
" This dose-response curve was shifted leftward when the effects of HMR1766 were investigated in isolated lungs from chronic hypoxic animals for 21 days at 10% oxygen."( The soluble guanylate cyclase activator HMR1766 reverses hypoxia-induced experimental pulmonary hypertension in mice.
Dahal, BK; Dumitrascu, R; Eickels, Mv; Fuchs, B; Ghofrani, HA; Grimminger, F; Hackemack, S; Medebach, T; Mittal, M; Pullamsetti, SS; Savai, R; Schermuly, RT; Seeger, W; Weissmann, N, 2009
)
" While low dosage of sodium danshensu produced small contraction possibly through transient enhancement of Ca(2+) influx, high dosage produced significant vasodilation mainly through promoting the opening of non-selective K(+) channels and small-conductance calcium-sensitive K(+) channels in the vascular smooth muscle cells."( Biphasic effects of sodium danshensu on vessel function in isolated rat aorta.
Chen, H; Gu, BQ; Huang, P; Jin, L; Mao, SL; Wang, J; Zhang, C; Zhang, N; Zhong, MF; Zou, H, 2010
)
"01) in dose-response studies enhanced human osteoblasts' proliferation."( Vessel dilator and C-type natriuretic peptide enhance the proliferation of human osteoblasts.
Bennett, M; Lenz, A; Skelton, WP; Vesely, DL, 2010
)
" We found a dose-response relationship between 8-Br-cGMP (0."( Protein kinase G inhibits basal and stimulated nitric oxide synthase activity in neonatal ovine lung microvascular endothelial cells.
John, TA, 2010
)
" In each case, the dose-response curve for N(2)O was progressively shifted to the right by increasing the dose of each pretreatment drug."( Involvement of a NO-cyclic GMP-PKG signaling pathway in nitrous oxide-induced antinociception in mice.
Chung, E; Ohgami, Y; Quock, LP; Quock, RM; Zhang, Y, 2011
)
" Their acute effects on BP and vascular function, important for daily dosing scheme, were studied in a placebo-controlled double-blind crossover study using a single oral dose of a fermented milk product containing Ile-Pro-Pro and Val-Pro-Pro as well as plant sterols."( Ile-Pro-Pro and Val-Pro-Pro tripeptide-containing milk product has acute blood pressure lowering effects in mildly hypertensive subjects.
Ehlers, PI; Filler, I; Jähnchen, E; Järvenpää, S; Kivimäki, AS; Korpela, R; Turpeinen, AM; Vapaatalo, H; Wagner, F; Wiegert, E, 2011
)
" The longer half-life of tadalafil allows for once-daily dosing as compared with three-times daily dosing for sildenafil, the only other PDE-5 inhibitor currently approved for treatment of PAH."( Tadalafil for the treatment of pulmonary arterial hypertension.
Klinger, JR, 2011
)
" In addition, the dosage of nitrite in the homogenized paw, as determined by colorimetric assay, indicated that exogenous PEA is able to induce NO release."( Involvement of the L-arginine/nitric oxide/cyclic guanosine monophosphate pathway in peripheral antinociception induced by N-palmitoyl-ethanolamine in rats.
Cortes, SF; Duarte, ID; Galdino, GS; Perez, AC; Resende, LC; Romero, TR; Silva, GC, 2012
)
" Dose-response curves were also constructed for pre-incubation of vascular rings with Nω-nitro-L-arginine methyl ester (L-NAME) (a non-specific nitric oxide synthase inhibitor), indomethacin (an unspecific cyclooxygenase inhibitor), and 1H-[1,2,4] oxadiazolo [4,3-a]quinoxalin-1-one (ODQ) (a guanylyl cyclase inhibitor)."( The lignan (-)-cubebin inhibits vascular contraction and induces relaxation via nitric oxide activation in isolated rat aorta.
Andrade E Silva, ML; Bastos, JK; Carvalho, MT; Celotto, AC; Cunha, WR; Evora, PR; Rezende, KC, 2013
)
" Cardioprotective effects were found over a broad dosage range."( Pharmacological postconditioning by bolus injection of phosphodiesterase-5 inhibitors vardenafil and sildenafil.
Böhme, S; Ebner, A; Ebner, B; Reetz, A; Schauer, A; Strasser, RH; Weinbrenner, C, 2013
)
" Using the patch-clamp technique in whole-cell configuration, we showed how l-cis-Diltiazem (a CNG-channel inhibitor) and KT5823 (a PKG inhibitor) decreased significantly the amplitude of macroscopic ion currents in a dose-response manner, and decreased in vitro capacitation."( Capacitation and Ca(2+) influx in spermatozoa: role of CNG channels and protein kinase G.
Cisneros-Mejorado, A; Hernández-Soberanis, L; Islas-Carbajal, MC; Sánchez, D, 2014
)
" Furthermore, dosage response studies showed that icariin at 10(-6)M (a physiologically achievable concentration in vivo) also activated this signal pathway."( Icariin stimulates the osteogenic differentiation of rat bone marrow stromal cells via activating the PI3K-AKT-eNOS-NO-cGMP-PKG.
Chen, KM; Ge, BF; Guo, XY; Ma, HP; Ma, XN; Xian, CJ; Zhai, YK; Zhen, P; Zhou, J, 2014
)
" Similar histopathological bone changes were observed in both young (7- to 9-week-old) and aged (42- to 46-week-old) rats when dosed by oral gavage with 3 different heme-dependent sGC agonist (sGCa) compounds or 1 structurally distinct heme-independent sGCa compound."( Oral administration of soluble guanylate cyclase agonists to rats results in osteoclastic bone resorption and remodeling with new bone formation in the appendicular and axial skeleton.
Andresen, CJ; Bagi, CM; Homer, BL; Morris, DL; Morton, D; Tones, MA; Warneke, JA; Whiteley, LO, 2015
)
" Results showed that the fusion protein HSA-(BNP)2 activated human natriuretic peptide receptor A (hNPR-A) with potency similar to that of BNP, despite using a 10-fold higher dosage than BNP."( The effects of fusion structure on the expression and bioactivity of human brain natriuretic peptide (BNP) albumin fusion proteins.
Deng, L; Ding, Y; Fu, Q; Jin, J; Peng, Y; Wu, Y, 2014
)
" Together, these results uncover a hitherto uncharacterized role of PDE5/cGMP/PKG signaling in bone homeostasis and provide the evidence that long-term treatment with PDE5 inhibitors at a high dosage may potentially cause bone catabolism."( Inhibition of phosphodiesterase 5 reduces bone mass by suppression of canonical Wnt signaling.
Chen, HX; Gong, Y; Hong, D; Hu, XH; Ji, X; Shi, W; Wang, HB; Wang, JR; Wu, XM; Xu, CY, 2014
)
"L-Citrulline plus L-arginine supplementation caused a more rapid increase in plasma L-arginine levels and marked enhancement of NO bioavailability, including plasma cGMP concentrations, than with dosage with the single amino acids."( Oral supplementation with a combination of L-citrulline and L-arginine rapidly increases plasma L-arginine concentration and enhances NO bioavailability.
Hayashi, T; Ina, K; Kuzuya, M; Maeda, M; Morita, M; Ochiai, M; Yamaguchi, T, 2014
)
" More recently, tadalafil has been introduced allowing once daily dosing with apparently similar efficacy to sildenafil in children."( Risk-benefit considerations when prescribing phosphodiesterase-5 inhibitors in children.
Bentley, S; Magee, AG; Makhecha, S, 2015
)
"MS and MK-801 showed biphasic and linear dose-response pattern, respectively."( The antinociceptive effects of magnesium sulfate and MK-801 in visceral inflammatory pain model: The role of NO/cGMP/K(+)ATP pathway.
Prostran, M; Savic Vujovic, K; Srebro, D; Vuckovic, S, 2015
)
" Multiple-dose studies in hypertensive patients showed that the blood-pressure-lowering effect diminished after 10 days, and 28-day studies showed that the hemodynamic effects were completely lost by day 28, even when the dose of MK-8150 was increased during the dosing period."( Discovery and Clinical Evaluation of MK-8150, A Novel Nitric Oxide Donor With a Unique Mechanism of Nitric Oxide Release.
Ali, A; Azer, K; Cully, D; de Kam, PJ; Denef, JF; Ederveen, AG; Gutstein, DE; Jonathan, D; Knox, CD; Liu, W; Lo, MM; Meehan, AG; Mitra, K; Mitselos, A; Morabito, C; Reynders, T; Shevell, D; Sun, SY; Wong, P, 2016
)
" Our theory was first able to clarify the conditions of attraction and repulsion, which are determined by balance between activator and inhibitor, and the conditions of uni- and bi-directional responses, which are determined by dose-response profiles of activator and inhibitor to the guidance cue."( Multi-phasic bi-directional chemotactic responses of the growth cone.
Hong, K; Igarashi, Y; Ishii, S; Naoki, H; Nishiyama, M; Togashi, K, 2016
)
"Sildenafil and tadalafil are widely-used phosphodiesterase 5 (PDE5) inhibitors for which no clear dose-response relationship could be established."( Cyclic guanosine monophosphate modulates accumulation of phosphodiesterase 5 inhibitors in human platelets.
Bajraktari, G; Bugert, P; Burhenne, J; Haefeli, WE; Weiss, J, 2017
)
" Ocular safety tolerability, exposure, and efficacy studies were conducted in rabbit and monkey models following topical ocular dosing of MGV354."( A Novel Selective Soluble Guanylate Cyclase Activator, MGV354, Lowers Intraocular Pressure in Preclinical Models, Following Topical Ocular Dosing.
Adams, C; Ehara, T; Ferrara, L; Ghosh, M; Kim, S; Li, B; McAllister, C; Mogi, M; Newton, R; Ng, CTH; Prasanna, G; Rice, DS; Stacy, R; Topley, T; Towler, C; Xiang, C; Yang, L, 2018
)
" The MGV354-induced IOP lowering was sustained up to 7 days following once-daily dosing in a monkey model of glaucoma and was greater in magnitude compared to Travatan (travoprost)-induced IOP reduction."( A Novel Selective Soluble Guanylate Cyclase Activator, MGV354, Lowers Intraocular Pressure in Preclinical Models, Following Topical Ocular Dosing.
Adams, C; Ehara, T; Ferrara, L; Ghosh, M; Kim, S; Li, B; McAllister, C; Mogi, M; Newton, R; Ng, CTH; Prasanna, G; Rice, DS; Stacy, R; Topley, T; Towler, C; Xiang, C; Yang, L, 2018
)
" Repeated once-daily dosing showed sustained decreases in BP."( A Randomized, Placebo-Controlled, Multiple-Ascending-Dose Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of the Soluble Guanylate Cyclase Stimulator Praliciguat in Healthy Subjects.
Chickering, JG; Currie, MG; Hall, M; Hanrahan, JP; Mihova, M; Milne, GT; Profy, AT; Ruff, D; Wakefield, JD; Wilson, PJ, 2019
)
"CSM cells obtained from 8 to 10 week old Sprague-Dawley rats were grown in Dulbecco media with 20% fetal calf serum and then incubated with or without l-arginine (L-ARG) or l-citrulline (L-CIT) in a time course and dose-response manner."( Exogenous l-ARGININE does not stimulate production OF NO or cGMP within the rat corporal smooth muscle cells in culture.
Abraham, A; Artaza, JN; Ferrini, MG; Flores, M; Graciano, L; Luna, R; Nguyen, S; Rajfer, J, 2019
)
" The data have implications for developing novel, non-prostaglandin therapeutics for IOP-lowering and cytoprotective effects with the possibility of an eye drop dosing regimen of once every 3 days for patients with glaucoma."( Nanoencapsulated hybrid compound SA-2 with long-lasting intraocular pressure-lowering activity in rodent eyes.
Acharya, S; Behera, S; Chaphalkar, RM; Ellis, DZ; Kodati, B; Krishnamoorthy, RR; Millar, JC; Nguyen, KT; Nguyen, T; Stankowska, DL, 2021
)
" NCX 667 or vehicle (30 µL) was instilled in a crossover, masked fashion and intraocular pressure (IOP) measured before dosing (baseline) and for several hours thereafter."( NCX 667, a Novel Nitric Oxide Donor, Lowers Intraocular Pressure in Rabbits, Dogs, and Non-Human Primates and Enhances TGFβ2-Induced Outflow in HTM/HSC Constructs.
Ahmed, F; Almirante, N; Bastia, E; Bergamini, MVW; Brambilla, S; Galli, C; Impagnatiello, F; Masini, E; Navratil, T; Sgambellone, S; Toris, CB; Torrejon, KY; Unser, AM, 2021
)
" In rats, microinjections of QA and vehicle were administered into the right and left hemispheres of striatum, respectively, and then rats were dosed daily with either CYR119 (10 mg/kg) or vehicle for 7 days."( The CNS-penetrant soluble guanylate cyclase stimulator CYR119 attenuates markers of inflammation in the central nervous system.
Atwater, E; Bernier, SG; Carvalho, A; Correia, SS; Currie, MG; Germano, P; Hadcock, JR; Iyengar, RR; Jacobson, S; Jones, JE; Liu, G; Lonie, E; Rivers, S; Schwartzkopf, CD; Tang, K; Tobin, JV; Winrow, CJ, 2021
)
" Following oral dosing in rats, CYR119 crossed the blood-brain barrier (BBB) and stimulated an increase in cGMP levels in the cerebral spinal fluid (CSF)."( The CNS-penetrant soluble guanylate cyclase stimulator CYR119 attenuates markers of inflammation in the central nervous system.
Atwater, E; Bernier, SG; Carvalho, A; Correia, SS; Currie, MG; Germano, P; Hadcock, JR; Iyengar, RR; Jacobson, S; Jones, JE; Liu, G; Lonie, E; Rivers, S; Schwartzkopf, CD; Tang, K; Tobin, JV; Winrow, CJ, 2021
)
" The effects of low cGMP levels on inflammation are unknown, therefore a dose-response effect of cGMP on inflammatory markers was assessed in THP-1 monocytes challenged with lipopolysaccharide (LPS)."( Modulation of Inflammatory Cytokine Production in Human Monocytes by cGMP and IRAK3.
Axell, A; Irving, HR; Meehan-Andrews, T; Nguyen, TH; Turek, I; Wright, B, 2022
)
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (5)

RoleDescription
plant metaboliteAny eukaryotic metabolite produced during a metabolic reaction in plants, the kingdom that include flowering plants, conifers and other gymnosperms.
human metaboliteAny mammalian metabolite produced during a metabolic reaction in humans (Homo sapiens).
Saccharomyces cerevisiae metaboliteAny fungal metabolite produced during a metabolic reaction in Baker's yeast (Saccharomyces cerevisiae).
Escherichia coli metaboliteAny bacterial metabolite produced during a metabolic reaction in Escherichia coli.
mouse metaboliteAny mammalian metabolite produced during a metabolic reaction in a mouse (Mus musculus).
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (2)

ClassDescription
3',5'-cyclic purine nucleotide
guanyl ribonucleotideA purine ribonucleotide where the purine is guanine.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Pathways (43)

PathwayProteinsCompounds
Hemostasis23944
Platelet homeostasis1827
Nitric oxide stimulates guanylate cyclase313
cGMP effects32
Signaling Pathways1269117
Visual phototransduction6241
The phototransduction cascade2621
Activation of the phototransduction cascade108
Inactivation, recovery and regulation of the phototransduction cascade2518
Signaling by WNT14820
Beta-catenin independent WNT signaling8113
Ca2+ pathway1612
MAPK family signaling cascades11519
ERK1/ERK2 pathway9319
RAF/MAP kinase cascade9119
Muscle contraction7721
Smooth Muscle Contraction2015
guanosine nucleotides degradation II125
adenosine nucleotides degradation I327
superpathway of purines degradation in plants745
superpathway of guanosine nucleotides degradation (plants)227
guanosine nucleotides degradation I226
purine nucleotides degradation I (plants)334
Purine nucleotides and Nucleosides metabolism ( Purine nucleotides and Nucleosides metabolism )10577
Joubert syndrome45
Thyroid hormones production and peripheral downstream signaling effects2216
Renz2020 - GEM of Human alveolar macrophage with SARS-CoV-20490
RAS processing1318
RAS and bradykinin pathways in COVID-19113
Sensory Perception21568
Antiviral and anti-inflammatory effects of Nrf2 on SARS-CoV-2 pathway16
Sildenafil treatment07
Female steroid hormones in cardiomyocyte energy metabolism73
Cardiomyocyte signaling pathways converging on Titin06
Dauer formation02
Vascular smooth muscle contraction013
MicroRNAs in cardiomyocyte hypertrophy04
Endothelin pathways013
Cardiac hypertrophic response05
Myometrial relaxation and contraction pathways02
NO/cGMP/PKG mediated neuroprotection016
Phosphodiesterases in neuronal function013
Thermogenesis018

Protein Targets (5)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Phosphodiesterase Bos taurus (cattle)IC50 (µMol)0.10000.10005.88009.9000AID159198
cGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)IC50 (µMol)2.40000.00002.072410.0000AID159203
cGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)IC50 (µMol)2.40000.00031.990110.0000AID159203
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Other Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Multidrug resistance-associated protein 4Homo sapiens (human)Km9.69001.90004.27259.6900AID679496
Multidrug resistance-associated protein 5Homo sapiens (human)Km2.10002.10002.10002.1000AID680352
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (46)

Processvia Protein(s)Taxonomy
negative regulation of cell adhesionPhosphodiesterase Bos taurus (cattle)
negative regulation of angiogenesisPhosphodiesterase Bos taurus (cattle)
negative regulation of lipid catabolic processPhosphodiesterase Bos taurus (cattle)
prostaglandin secretionMultidrug resistance-associated protein 4Homo sapiens (human)
cilium assemblyMultidrug resistance-associated protein 4Homo sapiens (human)
platelet degranulationMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic metabolic processMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
bile acid and bile salt transportMultidrug resistance-associated protein 4Homo sapiens (human)
prostaglandin transportMultidrug resistance-associated protein 4Homo sapiens (human)
urate transportMultidrug resistance-associated protein 4Homo sapiens (human)
glutathione transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
cAMP transportMultidrug resistance-associated protein 4Homo sapiens (human)
leukotriene transportMultidrug resistance-associated protein 4Homo sapiens (human)
monoatomic anion transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
export across plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
transport across blood-brain barrierMultidrug resistance-associated protein 4Homo sapiens (human)
guanine nucleotide transmembrane transportMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic metabolic processMultidrug resistance-associated protein 5Homo sapiens (human)
xenobiotic transmembrane transportMultidrug resistance-associated protein 5Homo sapiens (human)
purine nucleotide transportMultidrug resistance-associated protein 5Homo sapiens (human)
hyaluronan biosynthetic processMultidrug resistance-associated protein 5Homo sapiens (human)
glutathione transmembrane transportMultidrug resistance-associated protein 5Homo sapiens (human)
heme transmembrane transportMultidrug resistance-associated protein 5Homo sapiens (human)
xenobiotic transportMultidrug resistance-associated protein 5Homo sapiens (human)
transmembrane transportMultidrug resistance-associated protein 5Homo sapiens (human)
cAMP transportMultidrug resistance-associated protein 5Homo sapiens (human)
cGMP transportMultidrug resistance-associated protein 5Homo sapiens (human)
monoatomic anion transmembrane transportMultidrug resistance-associated protein 5Homo sapiens (human)
folate transmembrane transportMultidrug resistance-associated protein 5Homo sapiens (human)
export across plasma membraneMultidrug resistance-associated protein 5Homo sapiens (human)
transport across blood-brain barrierMultidrug resistance-associated protein 5Homo sapiens (human)
angiogenesiscGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
negative regulation of cell adhesioncGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
G protein-coupled receptor signaling pathwaycGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
negative regulation of angiogenesiscGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
cellular response to insulin stimuluscGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
negative regulation of cell adhesion mediated by integrincGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
negative regulation of lipid catabolic processcGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathwaycGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
cAMP-mediated signalingcGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
oocyte maturationcGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
lipid metabolic processcGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
G protein-coupled receptor signaling pathwaycGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
response to xenobiotic stimuluscGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
cAMP-mediated signalingcGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
cGMP-mediated signalingcGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
regulation of meiotic nuclear divisioncGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
negative regulation of apoptotic processcGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
negative regulation of vascular permeabilitycGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
positive regulation of vascular permeabilitycGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
steroid hormone mediated signaling pathwaycGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
negative regulation of cAMP-mediated signalingcGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
positive regulation of oocyte developmentcGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
regulation of ribonuclease activitycGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
cellular response to cGMPcGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
cellular response to transforming growth factor beta stimuluscGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
apoptotic signaling pathwaycGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
negative regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathwaycGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (29)

Processvia Protein(s)Taxonomy
metal ion bindingPhosphodiesterase Bos taurus (cattle)
guanine nucleotide transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
protein bindingMultidrug resistance-associated protein 4Homo sapiens (human)
ATP bindingMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type xenobiotic transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
prostaglandin transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
urate transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
purine nucleotide transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type glutathione S-conjugate transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type bile acid transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
efflux transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
15-hydroxyprostaglandin dehydrogenase (NAD+) activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATP hydrolysis activityMultidrug resistance-associated protein 4Homo sapiens (human)
glutathione transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATPase-coupled transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
xenobiotic transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ABC-type transporter activityMultidrug resistance-associated protein 4Homo sapiens (human)
ATP bindingMultidrug resistance-associated protein 5Homo sapiens (human)
organic anion transmembrane transporter activityMultidrug resistance-associated protein 5Homo sapiens (human)
ABC-type xenobiotic transporter activityMultidrug resistance-associated protein 5Homo sapiens (human)
purine nucleotide transmembrane transporter activityMultidrug resistance-associated protein 5Homo sapiens (human)
heme transmembrane transporter activityMultidrug resistance-associated protein 5Homo sapiens (human)
efflux transmembrane transporter activityMultidrug resistance-associated protein 5Homo sapiens (human)
ATP hydrolysis activityMultidrug resistance-associated protein 5Homo sapiens (human)
macromolecule transmembrane transporter activityMultidrug resistance-associated protein 5Homo sapiens (human)
glutathione transmembrane transporter activityMultidrug resistance-associated protein 5Homo sapiens (human)
ATPase-coupled transmembrane transporter activityMultidrug resistance-associated protein 5Homo sapiens (human)
xenobiotic transmembrane transporter activityMultidrug resistance-associated protein 5Homo sapiens (human)
ATPase-coupled inorganic anion transmembrane transporter activityMultidrug resistance-associated protein 5Homo sapiens (human)
carbohydrate derivative transmembrane transporter activityMultidrug resistance-associated protein 5Homo sapiens (human)
3',5'-cyclic-nucleotide phosphodiesterase activitycGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
3',5'-cyclic-AMP phosphodiesterase activitycGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
cGMP-inhibited cyclic-nucleotide phosphodiesterase activitycGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
protein bindingcGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
protein kinase B bindingcGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
metal ion bindingcGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
3',5'-cyclic-GMP phosphodiesterase activitycGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
3',5'-cyclic-nucleotide phosphodiesterase activitycGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
3',5'-cyclic-AMP phosphodiesterase activitycGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
cGMP-inhibited cyclic-nucleotide phosphodiesterase activitycGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
protein bindingcGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
nuclear estrogen receptor activitycGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
metal ion bindingcGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
3',5'-cyclic-GMP phosphodiesterase activitycGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
estrogen bindingcGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (13)

Processvia Protein(s)Taxonomy
membranePhosphodiesterase Bos taurus (cattle)
guanyl-nucleotide exchange factor complexPhosphodiesterase Bos taurus (cattle)
nucleolusMultidrug resistance-associated protein 4Homo sapiens (human)
Golgi apparatusMultidrug resistance-associated protein 4Homo sapiens (human)
plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
membraneMultidrug resistance-associated protein 4Homo sapiens (human)
basolateral plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
apical plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
platelet dense granule membraneMultidrug resistance-associated protein 4Homo sapiens (human)
external side of apical plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
plasma membraneMultidrug resistance-associated protein 4Homo sapiens (human)
Golgi lumenMultidrug resistance-associated protein 5Homo sapiens (human)
plasma membraneMultidrug resistance-associated protein 5Homo sapiens (human)
endosome membraneMultidrug resistance-associated protein 5Homo sapiens (human)
membraneMultidrug resistance-associated protein 5Homo sapiens (human)
basolateral plasma membraneMultidrug resistance-associated protein 5Homo sapiens (human)
apical plasma membraneMultidrug resistance-associated protein 5Homo sapiens (human)
membraneMultidrug resistance-associated protein 5Homo sapiens (human)
endoplasmic reticulumcGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
Golgi apparatuscGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
cytosolcGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
membranecGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
guanyl-nucleotide exchange factor complexcGMP-inhibited 3',5'-cyclic phosphodiesterase BHomo sapiens (human)
cytosolcGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
membranecGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
cytosolcGMP-inhibited 3',5'-cyclic phosphodiesterase AHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (29)

Assay IDTitleYearJournalArticle
AID680352TP_TRANSPORTER: uptake in membrane vesicles from MRP5-expressing V79 cells2000The Journal of biological chemistry, Sep-29, Volume: 275, Issue:39
The multidrug resistance protein 5 functions as an ATP-dependent export pump for cyclic nucleotides.
AID681362TP_TRANSPORTER: uptake in Xenopus laevis oocytes1997The Journal of biological chemistry, Jul-25, Volume: 272, Issue:30
Expression cloning and characterization of a novel multispecific organic anion transporter.
AID680357TP_TRANSPORTER: inhibition of E217betaG uptake (E217betaG: 30 uM, Zaprinast: 100uM) in MRP4-expressing HEK293 cells2003Molecular pharmacology, May, Volume: 63, Issue:5
Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5.
AID297178Activation of olfactory CNG A2A41b channel expressed in HEK293 cells assessed as effect on half maximal current2007Journal of medicinal chemistry, Aug-23, Volume: 50, Issue:17
Novel N7- and N1-substituted cGMP derivatives are potent activators of cyclic nucleotide-gated channels.
AID159198Inhibition of bovine arterial Phosphodiesterase 31996Journal of medicinal chemistry, Jan-05, Volume: 39, Issue:1
Studies of cardiotonic agents. 8. Synthesis and biological activities of optically active 6-(4-(benzylamino)-7-quinazolinyl)-4,5-dihydro-5-methyl-3(2H)- pyridazinone (KF15232).
AID297179Activation of retinal rod olfactory CNG A1B1 channel expressed in Xenopus oocytes assessed as effect on half maximal current2007Journal of medicinal chemistry, Aug-23, Volume: 50, Issue:17
Novel N7- and N1-substituted cGMP derivatives are potent activators of cyclic nucleotide-gated channels.
AID1219952Drug transport in human OAT2 expressed in HEK Flp-In cells at 0.05 uM for 10 mins relative to control2012Drug metabolism and disposition: the biological fate of chemicals, Mar, Volume: 40, Issue:3
Expression of organic anion transporter 2 in the human kidney and its potential role in the tubular secretion of guanine-containing antiviral drugs.
AID680353TP_TRANSPORTER: inhibition of alaninyl-d4TMP uptake (alaninyl-d4TMP: 1 uM, Zaprinast: 100uM) in MRP5-expressing HEK293 cells2003Molecular pharmacology, May, Volume: 63, Issue:5
Characterization of the transport of nucleoside analog drugs by the human multidrug resistance proteins MRP4 and MRP5.
AID680604TP_TRANSPORTER: inhibition of Estradiol-17beta-D-glucuronide uptake by cGMP at a concentration of 10 uM in membrane vesicle from MRP8-expressing LLC-PK1 cells2005Molecular pharmacology, Feb, Volume: 67, Issue:2
Transport of bile acids, sulfated steroids, estradiol 17-beta-D-glucuronide, and leukotriene C4 by human multidrug resistance protein 8 (ABCC11).
AID681922TP_TRANSPORTER: inhibition of E217betaG uptake (E217betaG: 1 uM, cGMP: 300 uM) in membrane vesicles from MRP4-expressing Sf9 cells2001The Journal of biological chemistry, Sep-07, Volume: 276, Issue:36
Transport of cyclic nucleotides and estradiol 17-beta-D-glucuronide by multidrug resistance protein 4. Resistance to 6-mercaptopurine and 6-thioguanine.
AID159203Inhibition of canine heart Phosphodiesterase 31996Journal of medicinal chemistry, Jan-05, Volume: 39, Issue:1
Studies of cardiotonic agents. 8. Synthesis and biological activities of optically active 6-(4-(benzylamino)-7-quinazolinyl)-4,5-dihydro-5-methyl-3(2H)- pyridazinone (KF15232).
AID588979Substrates of transporters of clinical importance in the absorption and disposition of drugs, MRP42010Nature reviews. Drug discovery, Mar, Volume: 9, Issue:3
Membrane transporters in drug development.
AID679496TP_TRANSPORTER: uptake in membrane vesicles from MRP4-expressing Sf9 cells2001The Journal of biological chemistry, Sep-07, Volume: 276, Issue:36
Transport of cyclic nucleotides and estradiol 17-beta-D-glucuronide by multidrug resistance protein 4. Resistance to 6-mercaptopurine and 6-thioguanine.
AID681904TP_TRANSPORTER: inhibition of MTX uptake (MTX: 20 uM, cGMP: 300 uM) in membrane vesicles from MRP4-expressing Sf9 cells2002Cancer research, Jun-01, Volume: 62, Issue:11
Analysis of methotrexate and folate transport by multidrug resistance protein 4 (ABCC4): MRP4 is a component of the methotrexate efflux system.
AID1346482Human CNGA1 (Cyclic nucleotide-regulated channels)1998Biophysical journal, Mar, Volume: 74, Issue:3
Functional co-assembly among subunits of cyclic-nucleotide-activated, nonselective cation channels, and across species from nematode to human.
AID1346482Human CNGA1 (Cyclic nucleotide-regulated channels)1995Proceedings of the National Academy of Sciences of the United States of America, Oct-24, Volume: 92, Issue:22
Mutations in the gene encoding the alpha subunit of the rod cGMP-gated channel in autosomal recessive retinitis pigmentosa.
AID1346529Rat CNGA2 (Cyclic nucleotide-regulated channels)1994Neuron, Sep, Volume: 13, Issue:3
A second subunit of the olfactory cyclic nucleotide-gated channel confers high sensitivity to cAMP.
AID1346505Human CNGA3 (Cyclic nucleotide-regulated channels)2003The Journal of biological chemistry, Jul-04, Volume: 278, Issue:27
Functionally important calmodulin-binding sites in both NH2- and COOH-terminal regions of the cone photoreceptor cyclic nucleotide-gated channel CNGB3 subunit.
AID1346529Rat CNGA2 (Cyclic nucleotide-regulated channels)2012Science signaling, Jul-10, Volume: 5, Issue:232
Differential regulation by cyclic nucleotides of the CNGA4 and CNGB1b subunits in olfactory cyclic nucleotide-gated channels.
AID1346482Human CNGA1 (Cyclic nucleotide-regulated channels)2002Neuron, Dec-05, Volume: 36, Issue:5
Rod cyclic nucleotide-gated channels have a stoichiometry of three CNGA1 subunits and one CNGB1 subunit.
AID1346482Human CNGA1 (Cyclic nucleotide-regulated channels)1992The Journal of neuroscience : the official journal of the Society for Neuroscience, Aug, Volume: 12, Issue:8
Human rod photoreceptor cGMP-gated channel: amino acid sequence, gene structure, and functional expression.
AID1346529Rat CNGA2 (Cyclic nucleotide-regulated channels)1994Proceedings of the National Academy of Sciences of the United States of America, Sep-13, Volume: 91, Issue:19
Heteromeric olfactory cyclic nucleotide-gated channels: a subunit that confers increased sensitivity to cAMP.
AID1346505Human CNGA3 (Cyclic nucleotide-regulated channels)1996FEBS letters, Sep-16, Volume: 393, Issue:2-3
Molecular cloning, functional expression and chromosomal localization of a human homolog of the cyclic nucleotide-gated ion channel of retinal cone photoreceptors.
AID1346482Human CNGA1 (Cyclic nucleotide-regulated channels)1995Neuron, Jan, Volume: 14, Issue:1
A histidine residue associated with the gate of the cyclic nucleotide-activated channels in rod photoreceptors.
AID1346487Rat CNGA3 (Cyclic nucleotide-regulated channels)2001Journal of neurophysiology, Jun, Volume: 85, Issue:6
Electrophysiological characteristics of rat gustatory cyclic nucleotide--gated channel expressed in Xenopus oocytes.
AID1346505Human CNGA3 (Cyclic nucleotide-regulated channels)1997The European journal of neuroscience, Dec, Volume: 9, Issue:12
Cloning, chromosomal localization and functional expression of the gene encoding the alpha-subunit of the cGMP-gated channel in human cone photoreceptors.
AID1346482Human CNGA1 (Cyclic nucleotide-regulated channels)1994Proceedings of the National Academy of Sciences of the United States of America, Nov-22, Volume: 91, Issue:24
Subunit 2 (or beta) of retinal rod cGMP-gated cation channel is a component of the 240-kDa channel-associated protein and mediates Ca(2+)-calmodulin modulation.
AID1346533Mouse HCN2 (Cyclic nucleotide-regulated channels)1998Nature, Jun-11, Volume: 393, Issue:6685
A family of hyperpolarization-activated mammalian cation channels.
AID1346482Human CNGA1 (Cyclic nucleotide-regulated channels)1999The Journal of general physiology, Jan, Volume: 113, Issue:1
C-Linker of cyclic nucleotide-gated channels controls coupling of ligand binding to channel gating.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (21,580)

TimeframeStudies, This Drug (%)All Drugs %
pre-19905930 (27.48)18.7374
1990's5974 (27.68)18.2507
2000's5195 (24.07)29.6817
2010's3616 (16.76)24.3611
2020's865 (4.01)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials333 (1.49%)5.53%
Reviews1,916 (8.57%)6.00%
Case Studies53 (0.24%)4.05%
Observational2 (0.01%)0.25%
Other20,042 (89.69%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]