vasoactive-intestinal-peptide has been researched along with zaprinast* in 8 studies
8 other study(ies) available for vasoactive-intestinal-peptide and zaprinast
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5-HT7 receptor-mediated relaxation of the oviduct in nonpregnant proestrus pigs.
The effects of 5-hydroxytryptamine (5-HT) on the muscle tonus of the ampulla and isthmus of the oviduct isolated from nonpregnant proestrus pigs were investigated, and the 5-HT receptor subtype and mechanisms of the responses were analyzed. 5-HT (1 nM-10 microM) caused a relaxation of longitudinal and circular muscles of the isthmus in a concentration-dependent manner. Tetrodotoxin did not change the relaxation, indicating a direct action of 5-HT on smooth muscle cells. The EC(50) value in the longitudinal muscle was significantly lower than that in the circular muscle but the maximum relaxations were similar. 5-HT also caused a relaxation of both muscle layers in the ampulla but the maximum relaxation of both muscles was smaller than that of the isthmus. 5-Carboxamidotryptamine (5-CT), 5-methoxytryptamine (5-MeOT) and (+/-)-8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) mimicked the relaxation of the isthmic longitudinal muscle by 5-HT, and the ranking order was 5-CT>5-HT>5-MeOT>8-OH-DPAT. On the other hand, oxymethazoline, 2-methyl-5-hydroxytryptamine (2-methyl-5-HT), alpha-methyl-5-hydroxytryptamine (alpha-methyl-5-HT), [endo-N-8-methyl-8-azabicyclo-(3,2,1) oct-3-yl]-2,3-dihydro-3-ethyl-2-oxo-1H-benzimidazol-1-carboxamide (BIMU-1), ergotamine and dihydroergotamine were less effective. The relaxation by 5-HT was not decreased by ketanserin, 2-methoxy-4-amino-5-chlorobenzoic acid 2-(diethylamino)ethyl ester (tropisetron) or [1[2-(methylsulphonyl) amino ethyl]-4-piperidinyl]methyl-1-methyl-1H-indole-3-carboxylate (GR113808) but was antagonized by the following compounds in a competitive manner (with pK(b) values in parentheses): 2a-[4-(4-phenyl-1,2,3,6-tetrahydropyridyl)butyl]-2a,3,4,5-tetrahydro-benzo[cd]indol-2(1H)-one (DR4004, 9.31), methiothepin (8.91), methysergide (7.95), metergoline (7.98), mianserin (7.69), mesulergine (8.4), spiperone (6.86) and clozapine (7.4). The correlation of these pK(b) values with pK(i) values of cloned 5-HT(7) receptor or pA(2) values of porcine uterus was high and significant. 4-(3-Butoxy-4-methoxybenzyl)-imidazolidin-2-one (Ro20-1724) significantly enhanced the relaxation by 5-HT but zaprinast, 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and L-nitroarginine methylester (L-NAME) did not change the responses to 5-HT. 5-HT increased cyclic AMP in the isthmic oviduct. Ampulla and isthmus contained a single class of [3H]5-CT binding sites with a similar K(d) value (0.4 nM), but the density of the receptors in the i Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Animals; Binding, Competitive; Cyclic AMP; Dose-Response Relationship, Drug; Enzyme Inhibitors; Estrous Cycle; Female; Guanylate Cyclase; Imidazoles; In Vitro Techniques; Isoproterenol; Muscle Relaxation; Neuropeptides; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Nitroprusside; Oviducts; Oxadiazoles; Pituitary Adenylate Cyclase-Activating Polypeptide; Purinones; Quinoxalines; Radioligand Assay; Receptors, Serotonin; Serotonin; Serotonin Antagonists; Serotonin Receptor Agonists; Swine; Tritium; Vasoactive Intestinal Peptide | 2003 |
Peptidergic and nitrergic inhibitory neurotransmissions in the hamster jejunum: regulation of vasoactive intestinal peptide release by nitric oxide.
Regulation of vasoactive intestinal peptide (VIP) release by nitric oxide (NO) was investigated in the hamster jejunum. Electrical field stimulation and applied NO (3-100 microM) evoked biphasic hyperpolarizations consisting of an initial transient hyperpolarizing component followed by a second more slowly developing component (late component). The NO synthase inhibitor N(G)-nitro-L-arginine methyl ester (200 microM) abolished the biphasic inhibitory junction potential evoked by electrical field stimulation. The NO scavenger oxyhemoglobin (50 microM) and the guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ; 10 microM) abolished both components of the inhibitory junction potentials and the NO-induced hyperpolarizations. VIP(6-28) (1 microM), which abolished VIP (3 microM)-induced hyperpolarizations, also inhibited the late components of the inhibitory junction potentials and the NO-induced hyperpolarizations. ODQ inhibited VIP release and cAMP production by electrical field stimulation and NO application. N(6)-2,0-Dibutyryladenosine 3',5'-cyclic monophosphate (0.1-3 mM) caused a membrane hyperpolarization. These results suggest that NO may stimulate VIP release from enteric nerves in the hamster jejunum. In addition, we propose that NO and NO-stimulated VIP contribute to the early and late components of the inhibitory junction potentials, respectively, in the circular smooth muscle cells of the hamster jejunum. Topics: Animals; Cricetinae; Cyclic AMP; Cyclic GMP; Electric Stimulation; Enzyme Inhibitors; Guanylate Cyclase; Jejunum; Male; Membrane Potentials; Mesocricetus; Muscle, Smooth; Myenteric Plexus; Neural Inhibition; NG-Nitroarginine Methyl Ester; Nitrergic Neurons; Nitric Oxide; Oxadiazoles; Oxyhemoglobins; Peptide Fragments; Phosphodiesterase Inhibitors; Purinones; Rolipram; Synaptic Transmission; Vasoactive Intestinal Peptide | 2002 |
Okadaic acid inhibits relaxant neural transmission in rat gastric fundus in vitro.
The aim of the present study was to characterize the influence of the phosphatase type 1 and 2A inhibitor okadaic acid on non-adrenergic, non-cholinergic (NANC) neurotransmission in the rat gastric fundus. Okadaic acid (10-6 M), an inhibitor of protein phosphatases 1 and 2A, did not show any influence on the basal tonus or on a contraction plateau induced by 5-HT (10-7 M) within 30 min of observation. When okadaic acid (10-6 M) was applied 10 min prior to 5-HT (10-7 M), the contraction plateau of serotonin was unchanged. To investigate the inhibitory neurotransmission, the muscle strips were pre-contracted using 5-HT (10-7 M), and inhibitory stimuli were applied at the contraction plateau, which was stable over 30 min. The inhibitory effects of vasoactive intestinal peptide (VIP), nitric oxide (NO) and electrical field stimulation (EFS, 40 V, 0.5 ms, frequencies ranging from 0.5 to 16 Hz) were examined. When okadaic acid (10-6 M) was applied prior to EFS-induced NANC relaxation, significant attenuation of the inhibitory response was demonstrated (16 Hz: control: -92.4 +/- 1.9%; okadaic acid 10-7 M: -60.7 +/- 6.1%; okadaic acid 10-6 M: -25.3 +/- 3.4%; n=11; P < 0.01). By contrast, neither the concentration-dependent inhibitory actions of VIP (10-11-10-8 M) (VIP 10-8 M: -100%; VIP 10-8 M + okadaic acid 10-6 M: -89.9 +/- 8.3%; n=8; n.s) nor that of diethylamine nitric oxide (DEA-NO) (3 x 10-7-10-4 M) (DEA-NO 10-4 M: -95.3 +/- 8.4%; DEA-NO 10-4 M + okadaic acid 10-7 M: -98.3 +/- 6.3%; DEA-NO 10-4 M + okadaic acid 10-6 M: 96.5 +/- 7.6%; n=9; n.s.) on 5-HT induced contraction were altered by pre-incubation with okadaic acid (10-6 M). This is the first report that supports the concept that protein phosphatases 1 and 2A may contribute to the regulation of rat gastric fundus motility. The protein phosphatase inhibitor okadaic acid significantly reduces electrically induced inhibitory NANC responses, while leaving direct muscular effects of the inhibitory NANC neurotransmitters VIP and NO unaffected - suggesting a neural site of action. The potential roles of protein phosphatases on NANC neurotransmission remain to be clarified in detail, as this might offer a new pathway for modulating smooth-muscle function. Topics: Animals; Carbazoles; Electric Stimulation; Enzyme Inhibitors; Gastric Fundus; Gastrointestinal Agents; Hydrazines; In Vitro Techniques; Indoles; Male; Muscle Relaxation; Muscle, Smooth; Nitric Oxide; Nitric Oxide Donors; Nitroarginine; Nitrogen Oxides; Okadaic Acid; Oxadiazoles; Phosphodiesterase Inhibitors; Phosphoprotein Phosphatases; Purinones; Pyrroles; Quinoxalines; Rats; Rats, Wistar; Synaptic Transmission; Vasoactive Intestinal Peptide | 2002 |
Characterisation of nitrergic transmission in the isolated anococcygeus muscle of the female mouse.
Field stimulation of anococcygeus muscles from female mice produced frequency-dependent relaxations of carbachol-induced tone, which were independent of the oestrus cycle but were abolished by the nitric oxide synthase (NOS) inhibitor L-N(G)-nitroarginine (L-NOARG; 100 microM) and the soluble guanylyl cyclase inhibitor 1 H-[1,2,4]oxodiazolo[4,3-a]quinoxalin-1-one (ODQ; 5 microM); L-NOARG inhibition was reversed by L-, but not D-arginine. The selective phosphodiesterase V inhibitor zaprinast (1-130 microM) directly relaxed tone and enhanced both the amplitude and duration of field stimulation-induced relaxations; the effect on amplitude was greater at lower frequencies of stimulation, while increased duration dominated at higher frequencies. The duration, but not the amplitude, of relaxations to exogenous nitric oxide (NO; 15 microM) was also increased by zaprinast. The mouse anococcygeus provides a useful model for pharmacological investigation of nitrergic neurotransmission in female urogenital smooth muscle. Topics: 1-Methyl-3-isobutylxanthine; Animals; Catechols; Dose-Response Relationship, Drug; Electric Stimulation; Enzyme Inhibitors; Estrus; Female; Guanylate Cyclase; In Vitro Techniques; Mice; Muscle Relaxation; Muscle, Smooth; Nitric Oxide; Nitric Oxide Synthase; Nitroarginine; Oxadiazoles; Phosphodiesterase Inhibitors; Purinones; Quinoxalines; Synaptic Transmission; Vasoactive Intestinal Peptide; Vasodilator Agents | 1999 |
Relaxing effects of cyclic GMP and cyclic AMP-enhancing agents on the long-lasting contraction to endothelin-1 in the porcine coronary artery.
In the coronary circulation, endothelin-1 (ET-1) evokes spasms which are difficult to treat when the endothelial integrity is compromised. This study compares several classes of relaxing agents on already established contractions to ET-1 in an in vitro model using ring segments of the porcine left descending coronary artery (pLAD). All segments were precontracted with 10 nmol/L ET-1. The calcium channel blocker isradipine was 300 times more potent than verapamil, but was only a partial relaxant; the maximal relaxation obtained was 52 +/- 2% (n = 6). Atrial natriuretic peptide (ANP) was an equally potent relaxant of the ET-1 contraction; however, it too was an incomplete relaxant, maximal relaxation being < 60%. A 50% relaxation of the ET-1 contraction was obtained with 0.28 +/- 0.24 mumol/L ANP, n = 4 (IC50). Comparison of cyclic nucleotide analogues revealed a 30 times higher potency for 8-bromo-cyclic guanosine monophosphate (8-Br-cGMP)(IC50 44 +/- 11 mumol/L, n = 6) than for 8-bromo-cyclic adenosine monophosphate (8-Bi-cAMP) (IC50 1600 mumol/L, n = 6). The cyclic nucleotide phosphodiesterase (PDE) inhibitor milrinone, a PDE 3-inhibitor with an IC50 2.4 +/- 1.8 mumol/L, (n = 6) was 10 times more potent than rolipram (PDE 4-inhibitor), zaprinast (PDE 5-inhibitor) and vinpocentine (PDE 1-inhibitor). Withdrawal of these analogues and inhibitors from segments continuously exposed to 10 nmol/l ET-1 revealed that vinpocentine and 8-Br-cGMP were irreversible relaxants, in contrast to milrinone and 8-Br-cAMP. In conclusion, this study has demonstrated that cGMP-enhancing agents, such as the naturally occurring ANP, the calcium channel blocker isradipine, and the synthetic inhibitor of PDE 3, were the most effective relaxants of ET-1 evoked contractions in pLAD in vitro. Topics: 8-Bromo Cyclic Adenosine Monophosphate; Animals; Atrial Natriuretic Factor; Caffeine; Calcium Channel Blockers; Calcium Channels; Calcium Channels, L-Type; Colforsin; Coronary Vessels; Cyclic AMP; Cyclic GMP; Dose-Response Relationship, Drug; Endothelin-1; In Vitro Techniques; Isradipine; Milrinone; Muscle, Smooth, Vascular; Papaverine; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Purinones; Pyrrolidinones; Rolipram; Swine; Vasoactive Intestinal Peptide; Vasoconstriction; Vasodilation; Verapamil; Vinca Alkaloids | 1998 |
Relaxant influence of phosphodiesterase inhibitors in the cat gastric fundus.
The breakdown of the relaxation-inducing second messengers cAMP and cGMP is mediated by phosphodiesterases. Inhibitors of functionally present phosphodiesterases can be expected to induce relaxation by increasing the basic amount of cAMP and/or cGMP. In the cat gastric fundus, vinpocetine, which has some selectivity for phosphodiesterase type I, only induced contractions, but the inhibitors of type III [5-(4-acetimidophenyl)pyrazin-(1H)-one; SKF 94120], type IV (rolipram) and type V (zaprinast) phosphodiesterase all caused concentration-dependent relaxation, as did the non-specific phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). The most potent relaxant agent was rolipram (EC50 9 +/- 5 x 10(-7) M and 3 +/- 1 x 10(-7) M in longitudinal and circular smooth muscle strips, respectively). These results suggest that type III, IV and V phosphodiesterases are functionally present in the cat gastric fundus and are involved in the regulation of tone. The possible influence of the phosphodiesterase inhibitors on non-adrenergic non-cholinergic (NANC) relaxation induced by nitric oxide (NO), vasoactive intestinal polypeptide (VIP) and train and sustained electrical field stimulation was then tested. Rolipram (3 x 10(-8) M), SKF 94120 (10(-5) M) and IBMX (10(-6) M) did not potentiate any of the relaxant stimuli studied. Zaprinast (10(-5) M), the cGMP specific type V phosphodiesterase inhibitor, caused a significant increase of the relaxation induced by exogenous NO and by train electrical field stimulation. These stimuli are thought to induce relaxation via an increase of intracellular cGMP.(ABSTRACT TRUNCATED AT 250 WORDS) Topics: 1-Methyl-3-isobutylxanthine; Animals; Cats; Cyclic GMP; Dose-Response Relationship, Drug; Female; Gastric Fundus; In Vitro Techniques; Isoenzymes; Male; Muscle Relaxation; Nitric Oxide; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Purinones; Pyrrolidinones; Rolipram; Vasoactive Intestinal Peptide | 1995 |
Nitric oxide and VIP as co-transmitters of neurogenic relaxation of human airways.
Topics: Autonomic Nervous System; Bronchi; Humans; Muscle Relaxation; Nitric Oxide; Phosphodiesterase Inhibitors; Purinones; Pyrrolidinones; Rolipram; Vasoactive Intestinal Peptide | 1995 |
Modulation of relaxant responses evoked by a nitric oxide donor and by nonadrenergic, noncholinergic stimulation by isozyme-selective phosphodiesterase inhibitors in guinea pig trachea.
Nonadrenergic, noncholinergic relaxations were elicited by field stimulation (1-16 Hz, 1 msec, 8 V for 15 sec) of guinea pig trachea desensitized with capsaicin (3 microM), pretreated with atropine (1 microM), propranolol (1 microM), indomethacin (3 microM) and treated with alpha-chymotrypsin (2 U/ml) and contracted with 3 microM histamine. The effect of the phosphodiesterase (PDE) isozyme selective inhibitors siguazodan (PDE III-selective), rolipram (PDE IV-selective), denbufylline (PDE IV-selective) and zaprinast (PDE V-selective) was examined on the relaxant responses to field stimulation and on relaxations elicited by the nitric oxide donor 3-morpholinosydnonimine-N-ethylcarbamide (SIN-1). The response to field stimulation in the presence of alpha-chymotrypsin (the putative nitric oxide component), at all the frequencies tested, was potentiated significantly by the PDE IV inhibitors rolipram (1 and 10 microM) and denbufylline (3 and 10 microM) as were responses to SIN-1. The PDE V inhibitor zaprinast (30 microM) potentiated relaxations elicited by field stimulation at 8 and 16 Hz and also potentiated responses to SIN-1. The PDE III inhibitor siguazodan (1 microM), however, was without effect on relaxant responses to field stimulation or to SIN-1. These results suggest that the nitric oxide component of the nonadrenergic, noncholinergic relaxant response is mediated primarily via cyclic AMP whose action is inactivated by a PDE IV isozyme and also by cyclic GMP which is inactivated by a PDE V isozyme. Topics: 3',5'-Cyclic-AMP Phosphodiesterases; Animals; Atropine; Cyclic AMP; Cyclic GMP; Cyclic Nucleotide Phosphodiesterases, Type 3; Cyclic Nucleotide Phosphodiesterases, Type 4; Electric Stimulation; Guanidines; Guinea Pigs; Indomethacin; Isoenzymes; Muscle Relaxation; Nitric Oxide; Phosphodiesterase Inhibitors; Phosphoric Diester Hydrolases; Propranolol; Purinones; Pyridazines; Pyrrolidinones; Receptors, Adrenergic; Receptors, Cholinergic; Rolipram; Trachea; Vasoactive Intestinal Peptide; Xanthines | 1995 |