atrial-natriuretic-factor and anantin

atrial-natriuretic-factor has been researched along with anantin* in 15 studies

Other Studies

15 other study(ies) available for atrial-natriuretic-factor and anantin

ArticleYear
Role of atrial natriuretic peptide in mediating the blood pressure-independent natriuresis elicited by systemic inhibition of nitric oxide.
    Pflugers Archiv : European journal of physiology, 2015, Volume: 467, Issue:4

    While it is clearly recognized that increased intrarenal nitric oxide (NO) levels elicit natriuresis, confounding data showing that systemic nitric oxide synthase inhibition (NOSi) also increases sodium excretion (UNaV) poses a conundrum. This response has been attributed to the associated increases in arterial pressure (AP); however, the increases in AP and in UNaV are temporally dissociated. The changes in regional renal haemodynamics induced by NOSi could also contribute to the alterations of UNaV. To evaluate the roles of AP and non-AP mechanisms mediating the natriuresis, N ω-nitro-L-arginine methyl ester hydrochloride (L-NAME) was infused i.v. at doses ranging from 5 to 50 μg/kg/min in anaesthetized rats. UNaV, perfusion of the cortex (cortical blood flow, CBF) and medulla (medullary blood flow, MBF) with laser-Doppler flowmetry and glomerular filtration rate (GFR) were measured. UNaV increased from 0.6 ± 0.2 to 1.6 ± 0.1 μmol/kg/min (P < 0.05) with the lower nonpressor doses. With the higher doses, AP increased from 116 ± 4 to 122 ± 4 mmHg and UNaV increased from 1.1 ± 0.3 to 3.3 ± 0.7 μmol/min/g (P < 0.002). UNaV increased similarly in a group where renal AP was maintained at baseline levels. The associated reductions in CBF (17 ± 5 and 38 ± 5 %) and MBF (27 ± 6 and 52 ± 6 %) would be expected to attenuate rather than contribute to the natriuresis. Plasma atrial natriuretic peptide (ANP) concentrations increased significantly following NOSi. Anantin, a natriuretic peptide receptor-A blocker, prevented or reversed the L-NAME-induced natriuresis without altering the L-NAME-induced changes in AP or CBF. The results indicate that increased ANP and related natriuretic peptides mediate the AP-independent natriuresis, at least partly, elicited by systemic L-NAME infusion and help resolve the conundrum of natriuresis during systemic NOSi.

    Topics: Animals; Atrial Natriuretic Factor; Blood Pressure; Hemodynamics; Kidney; Male; Natriuresis; Nitric Oxide; Nitric Oxide Synthase; Peptides, Cyclic; Rats; Rats, Sprague-Dawley; Sodium

2015
Role of atrial natriuretic Peptide in oxytocin induced cardioprotection.
    Heart, lung & circulation, 2015, Volume: 24, Issue:1

    The purpose of this study was to determine whether endogenous atrial natriuretic peptide (ANP) contributes to the protective effect of neurohypophysial hormone oxytocin (OT) in heart preconditioning.. Sprague-Dawley male rats were subjected to 25 min regional ischaemia and 120 min reperfusion and were divided into eight groups. Oxytocin or an equivalent volume of saline was administrated intraperitoneally, 30 min before ischaemia. The OT receptor antagonist (atosiban), ANP receptor antagonist (anantin) and nitric oxide synthase inhibitor (L-NAME) were injected 10 min before OT. In other groups, atosiban, anantin and L-NAME were only administered 40 min prior to ischaemia.. Compared with the ischaemia/reperfusion group (I/R), alterations in infarct size, biochemical parameters [LDH (lactate dehydrogenase), CK-MB (creatine kinase-MB), MDA (malondialdehyde) plasma levels] and severity of ventricular arrhythmia due to I/R injury were attenuated and VF was abolished by OT treatment. These OT effects were eliminated by OT and ANP receptor blockers and nitric oxide synthase inhibitor, but anantin did not reverse the effect of OT in lipid peroxidation.. These findings demonstrate an important contributory role of ANP in the OT induced protection in myocardial ischaemia reperfusion. OT also reduced lipid peroxidation with a NO-dependent mechanism.

    Topics: Animals; Atrial Natriuretic Factor; Cardiotonic Agents; Enzyme Inhibitors; Hormone Antagonists; Lipid Peroxidation; Male; Myocardial Infarction; Myocardial Reperfusion Injury; NG-Nitroarginine Methyl Ester; Oxytocics; Oxytocin; Peptides, Cyclic; Rats; Rats, Sprague-Dawley; Vasotocin

2015
Potent and direct presynaptic modulation of glycinergic transmission in rat spinal neurons by atrial natriuretic peptide.
    Brain research bulletin, 2013, Volume: 99

    Atrial and brain natriuretic peptides (ANP and BNP) exist in the central nervous system and modulate neuronal function, although the locus of actions and physiological mechanisms are still unclear. In the present study we used rat spinal sacral dorsal commissural nucleus (SDCN) and hippocampal 'synaptic bouton' preparations, to record both spontaneous and evoked glycinergic inhibitory postsynaptic currents (sIPSCs and eIPSCs) in SDCN neurons, and the evoked excitatory postsynaptic currents (eEPSCs) in hippocampal CA3 neurons. ANP potently and significantly reduced the sIPSC frequency without affecting the amplitude. ANP also potently reduced the eIPSCs amplitude concurrently increasing the failure rate and the paired pulse ratio response. These ANP actions were blocked by anantin, a specific type A natriuretic peptide receptor (NPR-A) antagonist. The results clearly indicate that ANP acts directly on glycinergic presynaptic nerve terminals to inhibit glycine release via presynaptic NPR-A. The ANP effects were not blocked by the membrane permeable cGMP analog (8Br-cGMP) suggesting a transduction mechanisms not simply related to increasing cGMP levels in nerve terminals. BNP did not affect on glycinergic sIPSCs and eIPSCs. Moreover, both ANP and BNP had no effect on glutamatergic EPSCs in hippocampal CA3 neurons. The results indicate a potent and selective presynaptic inhibitory action of ANP on glycinergic transmission in spinal cord sensory circuits.

    Topics: 4-Aminopyridine; 6-Cyano-7-nitroquinoxaline-2,3-dione; Anesthetics, Local; Animals; Animals, Newborn; Atrial Natriuretic Factor; Cyclic GMP; Excitatory Amino Acid Antagonists; Excitatory Postsynaptic Potentials; Glycine; Hippocampus; Inhibitory Postsynaptic Potentials; Lidocaine; Neurons; Peptides, Cyclic; Potassium Channel Blockers; Presynaptic Terminals; Rats; Rats, Wistar; Spinal Cord; Thionucleotides

2013
Gradients of natriuretic peptide precursor A (NPPA) in oviduct and of natriuretic peptide receptor 1 (NPR1) in spermatozoon are involved in mouse sperm chemotaxis and fertilization.
    Journal of cellular physiology, 2012, Volume: 227, Issue:5

    Selective spermatozoa movement from storage of the oviduct to fertilization site is suggested to be a result of chemotaxis. In the present study, Natriuretic peptide precursor A (NPPA) induced sperm chemotaxis in capillaries and enhanced intracellular Ca(2+) level, both of which could be blocked by the Natriuretic Peptide Receptor 1 (NPR1) inhibitor anantin and the cGMP-dependent protein kinase (PKG) inhibitors, KT5823 and Rp-8-Br-PET-cGMPS. NPPA also increased spermatozoa kinetic parameters of VAP, VSL, LIN, STR, and BCF. Only 2.0% of positive staining for NPR1 was detected in fresh spermatozoa. The positive rate was increased in capacitated spermatozoa (20.5%), and further increased in spermatozoa of NPPA treatment (70.2%). Nppa mRNA level in the ampullae was significantly higher compared with that in isthmus and uterotubal junction, and NPPA protein had an ascending gradient (AG) from the uterotubal junction to ampullae in gonadotropin-treated mice. NPPA induced sperm chemotaxis in diestrus oviducts without a NPPA gradient, and sperm chemotaxis occurred in the oviducts of gonadotropin-treated mice. These effects were inhibited by anantin. Meanwhile, sperm chemotaxis also occurred in unilateral ovariectomized oviducts of gonadotropin-treated mice, in which the possible effect of follicular fluid and oocyte-cumulus mass were eliminated when ovulation occurs. Furthermore, anantin significantly decreased the rate of fertilization in a dose-dependent manner (0.1 µM, 57.1%; 1 µM, 33.8%) compared with control (78.5%). These results suggest that a NPPA gradient originating in the oviduct induces sperm chemotaxis by binding to its receptor NPR1 and then activating PKG pathway, and plays a physiological role in fertilization.

    Topics: Animals; Atrial Natriuretic Factor; Calcium; Chemotaxis; Female; Fertilization; Gonadotropins; Humans; Male; Mice; Natriuretic Peptide, C-Type; Oviducts; Peptides, Cyclic; Protein Precursors; Receptors, Atrial Natriuretic Factor; Spermatozoa

2012
Stimulation of aquaporin-mediated fluid transport by cyclic GMP in human retinal pigment epithelium in vitro.
    Investigative ophthalmology & visual science, 2012, Apr-24, Volume: 53, Issue:4

    The retinal pigment epithelium (RPE) expresses aquaporin-1 (AQP1) and components of the natriuretic peptide signaling pathway. We hypothesized that stimulation of the natriuretic signaling pathway in RPE with atrial natriuretic peptide (ANP) and with membrane-permeable analogs of cGMP would induce a net apical-to-basal transport of fluid.. The hypothesis was tested using human RPE cultures that retain properties seen in vivo. Confluent monolayers were treated with ANP or membrane-permeable cGMP analogs in the presence of anantin, H-8, and an AQP1 inhibitor, AqB013. Fluid movement from the apical to basal chambers was measured by weight and used to calculate net fluid transport.. Our results demonstrated a 40% increase in net apical-to-basal fluid transport by ANP (5 μM) that was inhibited completely by the ANP receptor antagonist anantin and a 60% increase in net apical-to-basal fluid transport in response to the extracellularly applied membrane-permeable cGMP analog pCPT-cGMP (50 μM), which was not affected by the protein kinase G inhibitor H-8. The aquaporin antagonist AqB013 (20 μM) inhibited the cGMP-stimulated RPE fluid flux.. The effect of cGMP is consistent with an enhancement of the net fluid flux in RPE mediated by AQP1 channels. Pharmacologic activation of cGMP signaling and concomitant stimulation of fluid uptake from the subretinal space could offer insights into a new approach to treating or reducing the risk of retinal detachment.

    Topics: Animals; Aquaporin 1; Atrial Natriuretic Factor; Biological Transport, Active; Blotting, Western; Cell Membrane Permeability; Cells, Cultured; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; Dose-Response Relationship, Drug; Humans; Isoquinolines; Peptides, Cyclic; Retinal Pigment Epithelium; Water; Xenopus laevis

2012
Identification of a possible role for atrial natriuretic peptide in MDMA-induced hyperthermia.
    Toxicology letters, 2011, Oct-10, Volume: 206, Issue:2

    MDMA (3,4-methylenedioxymethamphetamine) induces thermogenesis in a mitochondrial uncoupling protein 3-dependent manner. There is evidence that this hyperthermia is mediated in part by the lipolytic release of free fatty acids, that subsequently activate uncoupling protein 3 in skeletal muscle mitochondria. We hypothesize that atrial natriuretic peptide (ANP), a strong lipolytic mediator, may contribute to the induction and maintenance of MDMA-induced thermogenesis. The specific aims of this study were to (1) determine if ANP is released following MDMA administration, and (2) use the ANP receptor antagonist, Anantin, to ascertain the role of ANP in MDMA-induced hyperthermia. ANP levels were measured in plasma at baseline, 10, 20, 30 and 60 min following MDMA (40 mg/kg, sc) administration in 16 male Sprague-Dawley rats. A robust increase in ANP was seen within 10 min of MDMA administration. ANP levels returned to baseline at 20 min and then gradually rose over the 60 min monitoring period. The administration of Anantin (40 mg, ip), 15 min before and after MDMA, significantly attenuated the MDMA-induced hyperthermia. We conclude that ANP signaling contributes to the hyperthermia induced by MDMA.

    Topics: Animals; Antipyretics; Atrial Natriuretic Factor; Body Temperature Regulation; Fever; Hallucinogens; Male; N-Methyl-3,4-methylenedioxyamphetamine; Peptides, Cyclic; Pyrogens; Random Allocation; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor; Signal Transduction; Sympathomimetics; Time Factors

2011
Response of cardiac mast cells to atrial natriuretic peptide.
    American journal of physiology. Heart and circulatory physiology, 2007, Volume: 293, Issue:2

    Previously, our laboratory demonstrated that cardiac mast cell degranulation induces adverse ventricular remodeling in response to chronic volume overload. The purpose of this study was to investigate whether atrial natriuretic peptide (ANP), which is known to be elevated in chronic volume overload, causes cardiac mast cell degranulation. Relative to control, ANP induced significant histamine release from peritoneal mast cells, whereas isolated cardiac mast cells were not responsive. Infusion of ANP (225 pg/ml) into blood-perfused isolated rat hearts produced minimal activation of cardiac mast cells, similar to that seen in the control group. ANP also did not increase matrix metalloproteinase-2 activity, reduce collagen volume fraction, or alter diastolic or systolic cardiac function compared with saline-treated controls. In a subsequent study to evaluate the effects of natriuretic peptide receptor antagonism on volume overload-induced ventricular remodeling, anantin was administered to rats with an aortocaval fistula. Comparable increases of myocardial MMP-2 activity in treated and untreated rats with an aortocaval fistula were associated with equivalent decreases in ventricular collagen (P < 0.05 vs. sham-operated controls). Cardiac functional parameters and left ventricular hypertrophy were unaffected by anantin. We conclude that ANP is not a cardiac mast cell secretagogue and is not responsible for the cardiac mast cell-mediated adverse ventricular remodeling in response to volume overload.

    Topics: Animals; Aorta, Abdominal; Arteriovenous Fistula; Ascitic Fluid; Atrial Natriuretic Factor; Cell Degranulation; Collagen; Disease Models, Animal; Histamine Release; Hypertrophy, Left Ventricular; In Vitro Techniques; Male; Mast Cells; Matrix Metalloproteinase 2; Myocardium; Peptides, Cyclic; Rats; Rats, Sprague-Dawley; Vena Cava, Inferior; Ventricular Function, Left; Ventricular Remodeling

2007
Modulation by brain natriuretic peptide of GABA receptors on rat retinal ON-type bipolar cells.
    The Journal of neuroscience : the official journal of the Society for Neuroscience, 2006, Jan-11, Volume: 26, Issue:2

    Natriuretic peptides (NPs) may work as neuromodulators through their associated receptors [NP receptors (NPRs)]. By immunocytochemistry, we showed that NPR-A and NPR-B were expressed abundantly on both ON-type and OFF-type bipolar cells (BCs) in rat retina, including the dendrites, somata, and axon terminals. Whole-cell recordings made from isolated ON-type BCs further showed that brain natriuretic peptide (BNP) suppressed GABAA receptor-, but not GABAC receptor-, mediated currents of the BCs, which was blocked by the NPR-A antagonist anantin. The NPR-C agonist c-ANF [des(Gln18, Ser19, Gln20, Leu21, Gly22)ANF(4-23)-NH2] did not suppress GABAA currents. The BNP effect on GABAA currents was abolished with preincubation with the pGC-A/B antagonist HS-142-1 but mimicked by application of 8-bromoguanosine-3',5'-cyclomonophosphate. These results suggest that elevated levels of intracellular cGMP caused by activation of NPR-A may mediate the BNP effect. Internal infusion of the cGMP-dependent protein kinase G (PKG) inhibitor KT5823 essentially blocked the BNP-induced reduction of GABAA currents. Moreover, calcium imaging showed that BNP caused a significant elevation of intracellular calcium that could be caused by increased calcium release from intracellular stores by PKG. The BNP effect was blocked by the ryanodine receptor modulators caffeine, ryanodine, and ruthenium red but not by the IP3 receptor antagonists heparin and xestospongin-C. Furthermore, the BNP effect was abolished after application of the blocker of endoplasmic reticulum Ca2+-ATPase thapsigargin and greatly reduced by the calmodulin inhibitors W-7 and calmidazolium. We therefore conclude that the increased calcium release from ryanodine-sensitive calcium stores by BNP may be responsible for the BNP-caused GABAA response suppression in ON-type BCs through stimulating calmodulin.

    Topics: Animals; Atrial Natriuretic Factor; Caffeine; Calcium; Calcium Channels; Calcium Signaling; Calcium-Transporting ATPases; Calmodulin; Carbazoles; Cyclic GMP; Cyclic GMP-Dependent Protein Kinases; GABA-A Receptor Antagonists; gamma-Aminobutyric Acid; Guanylate Cyclase; Heparin; Imidazoles; Indoles; Inositol 1,4,5-Trisphosphate Receptors; Macrocyclic Compounds; Male; Membrane Potentials; Natriuretic Peptide, Brain; Oxazoles; Patch-Clamp Techniques; Peptide Fragments; Peptides, Cyclic; Polysaccharides; Protein Kinase Inhibitors; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor; Receptors, Cytoplasmic and Nuclear; Receptors, GABA; Receptors, GABA-A; Retinal Bipolar Cells; Ruthenium Red; Ryanodine; Ryanodine Receptor Calcium Release Channel; Thapsigargin

2006
Neurohumoral mechanism in the natriuretic action of intracerebroventricular administration of renin.
    Journal of the renin-angiotensin-aldosterone system : JRAAS, 2004, Volume: 5, Issue:1

    Intracerebroventricular (i.v.t.) administration of renin (R) decreases urinary volume and increases urinary sodium excretion. We investigated whether i.v.t.-R-induced natriuresis could be associated with the release of atrial natriuretic peptide (ANP), its interaction with renal ANP-A receptors (ANPR-A) and the subsequent increase of urinary cyclic 3-5 guanosine monophosphate (cGMP).. In i.v.t. cannulated rats, the left carotid artery was catheterised with PE-50 tubing for blood collection, renin was injected i.v.t. and arterial blood samples were collected at 0, 2, 5, 10 and 15 minutes of injection, and urinary sodium and cGMP excretion at 1-, 3- and 6-hour periods of urine collection. Plasma ANP levels and urinary cGMP were determined by radioimmunoassay, and each urine sample was analysed for sodium concentration using a flame photometer.. Our results demonstrate that i.v.t.-R administration increases plasma ANP levels after two minutes of injection and urinary cGMP concentration at 1-, 3- and 6 hour period of urine collection. The natriuretic action induced by i.v.t.-R was blunted by peripheral administration of anantin, an ANPR-A antagonist. We assessed the role of brain angiotensin II (Ang II) AT1-receptors on the i.v.t.-induced antidiuresis, natriuresis and cGMP urinary excretion, the last as an indirect index of ANP secretion. Blockade of brain Ang II AT1-receptors with losartan (LOS; 120 microg/3 microl, i.v.t.), inhibited the antidiuretic action and blocked the increased urinary sodium and cGMP excretion induced by i.v.t.-R (7.14 mGU/5 microl). The increase in urinary cGMP was independent of nitric oxide synthase stimulation, since L-NAME pre-treatment did not alter the renal actions induced by i.v.t.-R.. Our results suggest that there is a link between the brain and the kidney. The activation of brain angiotensinergic neurons and stimulation of AT1- receptors may stimulate the release of ANP to the circulation. The released ANP circulates to the kidneys where it acts through renal ANPR-As and the consequent increase in cGMP to produce natriuresis.

    Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Atrial Natriuretic Factor; Brain; Cyclic GMP; Diuresis; Injections, Intraventricular; Losartan; Male; Natriuresis; Neurotransmitter Agents; Peptides, Cyclic; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Receptors, Atrial Natriuretic Factor; Renin; Time Factors

2004
Reciprocal paracrine pathways link atrial natriuretic peptide and somatostatin secretion in the antrum of the stomach.
    Regulatory peptides, 2003, Jan-31, Volume: 110, Issue:2

    Atrial natriuretic peptide (ANP) as well as its receptor, NPR-A, have been identified in gastric antral mucosa, suggesting that ANP may act in a paracrine fashion to regulate gastric secretion. In the present study, we have superfused antral mucosal segments obtained from rat stomach to examine the paracrine pathways linking ANP and somatostatin secretion in this region.ANP (0.1 pM to 0.1 microM) caused a concentration-dependent increase in somatostatin secretion (EC(50), 0.3 nM). The somatostatin response to ANP was unaffected by the axonal blocker tetrodotoxin but abolished by addition of the selective NPR-A antagonist, anantin. Anantin alone inhibited somatostatin secretion by 18+/-3% (P<0.005), implying that endogenous ANP, acting via the NPR-A receptor, stimulates somatostatin secretion. Somatostatin (1 pM to 1 microM) caused a concentration-dependent decrease in ANP secretion (EC(50), 0.7 nM) that was abolished by addition of the somatostatin subtype 2 receptor (sst2) antagonist, PRL2903. Neutralization of ambient somatostatin with somatostatin antibody (final dilution 1:200) increased basal ANP secretion by 70+/-8% (P<001), implying that endogenous somatostatin inhibits ANP secretion. We conclude that antral ANP and somatostatin secretion are linked by paracrine feedback pathways: endogenous ANP, acting via the NPR-A receptor, stimulates somatostatin secretion, and endogenous somatostatin, acting via the sst2 receptor, inhibits ANP secretion.

    Topics: Animals; Antibodies; Atrial Natriuretic Factor; Dose-Response Relationship, Drug; Feedback, Physiological; Gastric Mucosa; Guanylate Cyclase; In Vitro Techniques; Paracrine Communication; Peptide Fragments; Peptides, Cyclic; Pyloric Antrum; Rats; Rats, Sprague-Dawley; Receptors, Atrial Natriuretic Factor; Receptors, Somatostatin; Somatostatin

2003
Natriuretic peptide-induced relaxation of myometrium from the pregnant guinea pig is not mediated by guanylate cyclase activation.
    The Journal of pharmacology and experimental therapeutics, 2001, Volume: 297, Issue:1

    We tested both relaxation and cGMP generation by atrial (ANP), brain (BNP), and C-type natriuretic peptide (CNP) in oxytocin-stimulated myometrium from near-term pregnant guinea pigs to investigate the ability and mechanism of natriuretic peptides to inhibit myometrial contractility. Myometrial strips were contracted by 10(-8) M oxytocin, and relaxation to the cumulative addition (10(-9)-10(-6) M) of the natriuretic peptides measured. Maximal relaxation to BNP was significantly greater than to ANP (52 versus 32% respectively; p < 0.05), whereas CNP failed to produce relaxation. However, the increase in cGMP produced by BNP (10(-7) M) was significantly less than that produced by ANP (10(-7) M) (4.5 versus 7.0 times basal; p < 0.05); CNP did not increase myometrial cGMP. Anantin, a competitive blocker of the guanylate cyclase A receptor, significantly reduced the increase in cGMP produced by ANP and BNP, but had no effect on relaxation induced by either peptide. Rp-8-Br-cGMP, an inhibitor of the cGMP-dependent protein kinase, did not alter BNP-induced relaxation. The atrial natriuretic peptide-fragment 4-23 amide, a natriuretic peptide clearance receptor agonist, failed to inhibit oxytocin-stimulated myometrial contraction. We conclude that natriuretic peptide induced relaxation of oxytocin-stimulated myometrium from the pregnant guinea pig is not mediated by either guanylate cyclase A or B activation, is independent of the cGMP pathway, and does not involve clearance receptor activation. Our results suggest that natriuretic peptide-induced relaxation of pregnant myometrium is mediated via a novel mechanism.

    Topics: Animals; Atrial Natriuretic Factor; Cyclic GMP; Female; Guanylate Cyclase; Guinea Pigs; Muscle Relaxation; Myometrium; Natriuretic Peptide, Brain; Oxytocin; Peptides, Cyclic; Pregnancy; Pregnancy, Animal; Uterine Contraction

2001
Activation of particulate guanylate cyclase by adrenomedullin in cultured SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells.
    Cellular signalling, 2000, Volume: 12, Issue:7

    We investigated the effects of adrenomedullin (ADM) on cGMP production in cultured SV-40 transformed cat iris sphincter smooth muscle (SV-CISM-2) cells. ADM increased cGMP accumulation in a time- and concentration- dependent manner. The peptide increased cGMP formation in the transformed cells by 405-fold as compared to 1. 6-fold in primary cultured CISM cells. The basal cGMP concentrations in both cell types were comparable. In addition, ADM increased cAMP accumulation in SV-CISM-2 cells and in primary cultured cells by 18. 9- and 5.8-fold, respectively. The ADM receptor antagonist, ADM(26-52), but not the atrial natriuretic peptide (ANP) receptor antagonist, anantin, inhibited ADM-induced cGMP formation. The phorbol ester, phorbol 12, 13-dibutyrate (PDBu), which inhibits particulate guanylate cyclases in smooth muscle, blocked ADM-stimulated cGMP accumulation. In contrast, inhibitors of the soluble guanylate cyclases, such as LY83583 and ODQ, and inhibitors of the nitric oxide cascade had little effect on ADM-stimulated cGMP production. The stimulatory effect of ADM on cGMP formation is due to activation of the guanylate cyclase system and not to a much reduced phosphodiesterase activity. ADM stimulated guanylate cyclase activity in membrane fractions isolated from SV-CISM-2 cells in a concentration-dependent manner with EC(50) value of 72 nM. Pertussis toxin, an activator of the G-protein, Gi, inhibited ADM-stimulated cGMP accumulation, whereas cholera toxin, a stimulator of the Gs G-protein and subsequently cAMP accumulation, had little effect. Pretreatment of the plasma membrane fraction with Gialpha antibody attenuated ADM-stimulated guanylate cyclase activity by 75%. We conclude that ADM increases intracellular cGMP levels in SV-CISM-2 cells through activation of the ADM receptor and subsequent stimulation of a Gi-mediated membrane-bound guanylate cyclase.

    Topics: Adjuvants, Immunologic; Adrenomedullin; Animals; Atrial Natriuretic Factor; Cats; Cell Line; Cell Line, Transformed; Cell Membrane; Cells, Cultured; Cholera Toxin; Cyclic AMP; Cyclic GMP; Dose-Response Relationship, Drug; Enzyme Activation; GTP-Binding Proteins; Guanylate Cyclase; Humans; Iris; Kinetics; Models, Biological; Muscle, Smooth; Peptides; Peptides, Cyclic; Pertussis Toxin; Time Factors; Vasodilator Agents; Virulence Factors, Bordetella

2000
A fluorescence study of tryptophan-histidine interactions in the peptide anantin and in solution.
    Photochemistry and photobiology, 1994, Volume: 60, Issue:1

    Anantin is a heptadecapeptide in which the C-terminal peptide chain pierces the covalently cyclized peptide ring formed by an amide link between the alpha-NH2 end group and the beta-carboxyl group of Asp(8). It contains a tryptophan and a histidine at positions 5 and 12, respectively. Des-Phe(17)-anantin lacks the C-terminal phenylalanine. Fluorescence emission intensity as a function of pH follows the ionization of a single residue. The pKa amounts to 7.23 +/- 0.03 for anantin and is attributed to His(12). At pH 9 the quantum yield is 0.12 +/- 0.01 for anantin, whereas at pH 4.5 the quantum yield decreases more than two-fold (0.05 +/- 0.01). Practically identical parameters are observed for des-Phe(17)-anantin. This pH dependency reveals intramolecular quenching of the excited indole ring of Trp(5) by the imidazole of His(12), which results in a marked decrease of the tryptophan fluorescence at low pH. In a multifrequency phase fluorometric study the fluorescence lifetimes for both peptides at pH 4.5 and pH 9 are determined. At both, pH fluorescence decay is well described by a sum of two exponentials. For anantin at pH 4.5 the lifetimes are 0.72 +/- 0.07 ns and 1.67 +/- 0.07 ns. At pH 9 the lifetimes are 1.11 +/- 0.12 ns and 2.55 +/- 0.03 ns. In methanol we find two lifetimes for anantin: 0.68 +/- 0.01 ns and 2.57 +/- 0.01 ns. The lifetimes are found to be slightly dependent upon emission wavelength. For des-Phe(17)-anantin practically the same values are observed.(ABSTRACT TRUNCATED AT 250 WORDS)

    Topics: Amino Acid Sequence; Atrial Natriuretic Factor; Chemical Phenomena; Chemistry, Physical; Drug Interactions; Histidine; Molecular Sequence Data; Peptides, Cyclic; Solutions; Spectrometry, Fluorescence; Tryptophan

1994
Anantin--a peptide antagonist of the atrial natriuretic factor (ANF). II. Determination of the primary sequence by NMR on the basis of proton assignments.
    The Journal of antibiotics, 1991, Volume: 44, Issue:2

    Anantin, a naturally occurring peptide from Streptomyces coerulescens, binds competitively to the receptor of atrial natriuretic factor (ANF) from bovine adrenal cortex (Kd = 0.6 microM) and acts as ANF antagonist. Protein chemical data and FAB-MS have identified anantin to be a cyclic polypeptide consisting of 17 common L-amino acids. The molecule is highly stable and precludes the application of standard sequencing methods. The primary sequence of anantin was determined by 2D 1H NMR spectroscopy and the application of advanced protein chemical methods to be Gly1-Phe2-Ile3-Gly4-Trp5-Gly6-Asn7-Asp8 -Ile9-Phe10-Gly11-His12-Tyr13-Ser14+ ++- Gly15-Asp16-Phe17. The molecule is cyclized between the beta-carboxyl group of Asp8 and the amino group of Gly1.

    Topics: Amino Acid Sequence; Amino Acids; Atrial Natriuretic Factor; Chromatography, High Pressure Liquid; Magnetic Resonance Spectroscopy; Mass Spectrometry; Molecular Sequence Data; Peptides, Cyclic

1991
Anantin--a peptide antagonist of the atrial natriuretic factor (ANF). I. Producing organism, fermentation, isolation and biological activity.
    The Journal of antibiotics, 1991, Volume: 44, Issue:2

    Anantin, a peptide binding to the receptor of the atrial natriuretic factor (ANF) was isolated from a strain of Streptomyces coerulescens. The molecule consists of 17 natural L-amino acids which form a peptidic ring system. It has a MW of 1,871.0. The chemical composition is C90H111N21O24. The compound was found to bind competitively to ANF-receptors from bovine adrenal cortex (Kd = 0.61 microM). Furthermore, it dose-dependently inhibited the ANF-induced intracellular cyclic guanosine monophosphate accumulation in bovine aorta smooth muscle cells. At the same concentration no agonistic effects were detectable in these cells. Thus, anantin is considered to be the first microbially produced antagonist of the cardiac hormone, ANF.

    Topics: Adrenal Cortex; Amino Acids; Animals; Atrial Natriuretic Factor; Binding, Competitive; Cattle; Chromatography, High Pressure Liquid; Cyclic GMP; Dose-Response Relationship, Drug; Esters; Fermentation; Mass Spectrometry; Muscle, Smooth, Vascular; Peptides, Cyclic; Receptors, Atrial Natriuretic Factor; Receptors, Cell Surface; Soil Microbiology; Spectrophotometry, Infrared; Streptomyces

1991
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