Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Contractions induced by [Arg8]vasopressin (vasopressin) and the effect of nonpeptide vasopressin receptor antagonists were studied in the human isolated coronary artery. Vasopressin induced contraction of coronary artery segments with a high pD2 (9.25) but a low Emax (11.8% of the response to 100 mM K+). This response was not affected by removal of the endothelium. Contraction was antagonized by the vasopressin V1 receptor antagonist SR 49059 ((2S) 1-[(2R 3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene- sulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2- carboxamide) (pA2: 9.76). OPC-31260 ([5-dimethylamino-1-(4-(2-methylbenzoylamino)benzoyl)-2,3,4,5-tetr ahydro-1H- benzazepine]: vasopressin V2 receptor antagonist) and OPC-21268 (1-(1-[4-(3-acetylaminopropoxy) benzoyl]-4-piperidyl)-3,4- dihydro-2(1H)-quinolinone: reported vasopressin V1 receptor antagonist) were less potent antagonists of vasopressin-induced contractions (pA2: 7.31 and 5.6, respectively). The antagonist potency order (SR 49059 > OPC-31260 > OPC-21268) corresponds to the reported affinity order for the human cloned vasopressin V1 receptor. Therefore, the vasopressin V1 receptor antagonist SR 49059, but not OPC-21268, appears to be an appropriate tool to investigate further the role of vasopressin in pathological processes involving coronary vasoconstriction in humans.
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PMID:[Arg8]vasopressin-induced responses of the human isolated coronary artery: effects of non-peptide receptor antagonists. 856 39

The renal vascular effects of [Arg8]vasopressin (vasopressin) were investigated in the isolated perfused rat kidney. Vasopressin (0.01-3 nM) elicited a dose-dependent vasoconstriction in kidneys from Sprague Dawley rats, with a EC50 value of 0.206 +/- 0.044 nM. Inhibition of nitric oxide synthase by N omega-nitro-L-arginine (100 microM) shifted the vasopressin-induced vasoconstrictor response curve to the left. Inhibition of cyclooxygenase by indomethacin (10 or 30 microM) blunted the constriction induced by low concentrations of the peptide. Vasopressin, like angiotensin II but not noradrenaline, induced tachyphylaxis, SR 49059 ((2S)1-[(2R,3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene- sulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2- carboxamide) (1-30 nM), a new potent and selective non-peptide vasopressin V1A receptor antagonist, shifted the concentration-response curve for vasopressin to the right without decreasing the maximum contraction. Antagonism became competitive with a pA2 value (+/- S.D.) of 9.72 +/- 0.20 during inhibition of nitric oxide release. [Mpa1,D-Arg8]Vasopressin (desmopressin; 0.1-100 nM), or vasopressin (0.01-1 nM) after blockade of the vasopressin V1A receptor by SR 49059, induced no vasopressin V2 receptor-related renal relaxation in kidneys with vascular tone previously restored by noradrenaline or prostaglandin F2 alpha. These findings indicate that in the isolated perfused rat kidney vasopressin is a potent renal vasoconstrictor. The constriction depends on activation of smooth muscle vasopressin V1A receptors and is modulated by endothelial nitric oxide but not by prostacyclin or vasopressin V2 receptor-related vasodilation.
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PMID:Vascular effects of [Arg8]vasopressin in the isolated perfused rat kidney. 895 54

gamma 2-Melanocyte-stimulating hormone (gamma 2-MSH) and related melanotropins have been shown to have various cardiovascular effects, including acute, short-lasting increases in blood pressure (MAP) and heart rate (HR). gamma 2-MSH, administered intravenously, dose-dependently increased MAP and HR with an ED50 of approximately 30 nmol/kg and a maximal effect on MAP of approximately 55 mm Hg and on HR of around 70 beats per minute. Intravenous (i.v.) pretreatment with the alpha 1-adrenoceptor antagonist, prazosin, caused the dose-response curve for the effect of gamma 2-MSH on MAP to shift to the right with a decrease in slope, whereas it had no effect on the dose-response curve for the effect on HR. I.v. pretreatment with the beta 1-adrenoceptor antagonist, metoprolol, had no effect on the dose-response curve for the effect of gamma 2-MSH on MAP, but it caused the dose-response curve for the effect of the peptide on HR to shift to the right with a decrease in slope. Neither i.v. nor intracerebroventricular (i.c.v.) administration of the vasopressin V1A receptor antagonist, SR 49059 ((2S) 1-[(2R 3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxy-benzene-sulfonyl)- 3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide), had significant effects on the dose-response curves for the effects of the peptide on either MAP or HR. The doses of prazosin, metoprolol and SR 49059 were found to be effective in counteracting the effects of agonists for these receptors (phenylephrine, isoprenaline and [Arg8]vasopressin, respectively). Taken together, these results support the postulate that the effects of gamma 2-MSH are, at least partially, due to an increase in sympathetic outflow to the periphery (Gruber and Callahan (1989), Am J Physiol 257: R681-R694), and that this increase leads to increased activation of vascular alpha 1-adrenoceptors and cardiac beta 1-adrenoceptors. If, as was suggested by these authors, gamma 2-MSH acts via activation of a central vasopressin system, it is via a vasopressin receptor subtype other than the vasopressin V1A receptor, since i.c.v. administration of a selective vasopressin V1A receptor antagonist failed to interfere with the pressor and cardioaccelerator effects of gamma 2-MSH.
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PMID:Influence of blockade of alpha 1-adrenoceptors, beta 1-adrenoceptors and vasopressin V1A receptors on the cardiovascular effects of gamma 2-melanocyte-stimulating hormone (gamma 2-MSH). 920 56

In isolated dog posterior ciliary arteries contracted with prostaglandin F2alpha, desmopressin (10(-10) to 10(-8) M), a vasopressin V2 receptor agonist, produced a concentration-related relaxation, which was reversed to a contraction by removal of the endothelium. Desmopressin was approximately 1/100 as potent as arginine vasopressin. Treatment with NG-nitro-L-arginine, a nitric oxide (NO) synthase inhibitor, reversed the desmopressin-induced relaxation to a contraction and the addition of L-arginine restored the relaxation. SR49059 ((2S)1-[(2 R3S)-(5-chloro-3-(2-chlorophenyl)-1-(3,4-methoxybenzene-s ulfony)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-car boxamide), a selective vasopressin V1 receptor antagonist, suppressed the relaxation. In endothelium-denuded arteries, desmopressin-induced contractions were also inhibited by SR49059. It is concluded that desmopressin, although much less potent than vasopressin, relaxes ciliary arteries via a mediation of NO synthesized from L-arginine in the endothelium. Vasopressin V1-receptor Subtypes appear to be involved in the desmopressin-induced relaxation and contraction.
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PMID:Desmopressin-induced dog ciliary artery relaxation. 960 Jun 55

Several studies indicate that oxytocin and vasopressin receptors in the human uterus are heterogeneous. We have investigated whether oxytocin and vasopressin bind to separate receptors or one class of receptors in human uterine smooth muscle cells. [3H]d(CH2)5Tyr(Me)AVP, the vasopressin V1A receptor selective radioligand, was used for comparison of vasopressin binding sites in human uterine and vascular smooth muscle cell membranes. Both membrane preparations exhibited one class of high-affinity binding sites with Kd values of 6.44 and 0.47 nM, Bmax values of 166 and 34.8 fmol/mg protein for uterine and vascular smooth muscle cells, respectively. In vascular preparations, the selective vasopressin V1A receptor antagonist, SR 49059 ((2S) 1-[(2R 3S)-(5-chloro-3-(2-chlorophenyl)- -(3.4-dimethoxybenzenesulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2- carbonyl]-pyrrolidine-2-carboxamide), showed high affinity with Ki value of 0.98 nM, confirming that these receptors belong to the vasopressin V1A receptor subtype. On the contrary, in uterine preparations, binding of [3H]d(CH2)5Tyr(Me)AVP was more effectively displaced by oxytocin and the oxytocin receptor selective antagonist, L-371257, (1-[1-[4-[ N-Acetyl-4-piperidinyl)oxy]2-methoxybenzoyl]piperidin-4-yl]- 4H-3,1-benzoxazin-2(1H)-one), than vasopressin and SR 49059, suggesting that binding may be due to cross-reaction with the oxytocin receptors. These results suggest that human uterine smooth muscle cells express only a high density of oxytocin receptors.
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PMID:Comparison of vasopressin binding sites in human uterine and vascular smooth muscle cells. 1047 74

Nitric oxide attenuates both vasopressin-induced vasoconstriction and vasopressin release. We tested whether hypertension and renal dysfunction elicited by chronic inhibition of nitric oxide (NO) synthesis using N(G)-nitro-L-arginine (L-NNA) could be mediated in part by vasopressin V(1A) receptors. Male rats were treated orally for 6 weeks with L-NNA (15 mg/kg per day), a nonpeptide V(1A) receptor antagonist (2S)-1-[(2R,3S)-5-chloro-3-(2-chlorophenyl)-1-(3, 4-dimethoxybenzene-sulfonyl)-3-hydroxy-2, 3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide (SR 49059, 30 mg/kg per day), or a combination of SR 49059 and L-NNA (same doses), or they received no treatment. Both drugs were added to the food. Measurements were performed in conscious rats (urine collection in metabolic cages, tail-cuff arterial pressure) and at the end of the study in anesthetized rats (clearance measurements). L-NNA produced sustained hypertension, decreased glomerular filtration rate, and increased renal vascular resistance, plasma renin activity, and urinary albumin excretion. SR 49059 had no effect per se on these parameters and also did not attenuate the hypertension and renal dysfunction induced by L-NNA. Surprisingly, SR 49059 potentiated L-NNA-induced hypertension at the end of the 6-week treatment. However, the blood pressure response and the renal and mesenteric vasoconstriction elicited by exogenous vasopressin were attenuated in rats treated with SR 49059. L-NNA did not change plasma vasopressin concentration or 24-hour urinary vasopressin excretion. Our findings suggest that activation of vasopressin V(1A) receptors does not contribute to the hypertension and renal dysfunction induced by chronic NO synthesis inhibition. They also document unchanged plasma vasopressin concentration in NO-deficient hypertension.
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PMID:Vasopressin does not effect hypertension caused by long-term nitric oxide inhibition. 1067 4

Evidence is increasing that therapeutic modulation of neurohormonal activation with vasopressin receptor antagonists via V(1A) and V(2) receptors may favourably affect prognosis of heart failure. This study was designed to compare in vivo hemodynamic effects of early treatment (1-21 days after infarction) with a V(1A) (SR-49059 or ((2S)1-[(2R3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene-sulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide); 0.3 mg/kg/day) and a V(2) (SR-121463B or (1-[4-(N-tert-Butylcarbamoyl)-2-methoxybenzene sulfonyl]-5-ethoxy-3-spiro-[4-(2-morpholinoethyoxy)-cyclo-hexane]indol-2one,furmate; 0.5 mg/kg/day) receptor antagonist in myocardial infarcted rats, chronically instrumented for hemodynamic measurements. Left ventricular dysfunction in conscious myocardial infarcted rats, which was evidenced by a significantly decreased cardiac output (myocardial infarction: 70+/-3 vs. sham: 81 +/- 3 ml/min) and stroke volume (myocardial infarction: 190 +/- 10 vs. sham: 221 +/- 7 microl), was restored by the vasopressin V(1A) (81+/-2 ml and 224 +/- 5 microl, respectively) but not V(2) receptor antagonist. Improved cardiac output with the vasopressin V(1A) receptor antagonist resulted from an increased stroke volume at a reduced myocardial infarction induced tachycardia. In addition to the hemodynamic measurements, left ventricular hypertrophy and capillary density were determined, histologically measured as the cross-sectional area of Gomori-stained myocytes and Lectin-stained capillaries per tissue area, respectively. The observed left ventricular concentric hypertrophy (myocardial infarction: 525 +/- 38 vs. sham: 347 +/- 28 microm(2); P < 0.05) and reduced capillary density (myocardial infarction: 2068 +/- 162 vs. sham: 2800 +/- 250 number/mm(2); P<0.05) in the spared myocardium of myocardial infarcted rats, remained unaffected by the vasopressin V(1A) or V(2) receptor antagonist. Thus, chronic vasopressin V(1A) but not V(2) receptor blockade prevents heart failure in 3-week-old infarcted rats. Moreover, the improved cardiac function could not attributed to changes in left ventricular hypertrophy and/or capillary density.
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PMID:Chronic vasopressin V(1A) but not V(2) receptor antagonism prevents heart failure in chronically infarcted rats. 1216 17

In the non-pregnant mouse myometrium, both arginine vasopressin and oxytocin induced contractions (pD(2)=8.55+/-0.13 and 9.23+/-0.09, respectively). The effect of oxytocin was the most potent, while the maximum contractions induced by these two peptides were almost of the same magnitude. Both vasopressin- and oxytocin-induced contractions were strongly inhibited by an oxytocin receptor antagonist, CL-12-42 (d(CH(2))(5)[Tyr(Me)(2),Thr(4),Tyr-NH(2)(9)]OVT), and weakly inhibited by a vasopressin V(1a) receptor antagonist, SR49059 ((2S)1-[(2R,3S)-5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene-sulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide). Similar results were obtained in the pregnant mouse myometrium. These results suggest that not only oxytocin- but also vasopressin-induced contraction is mediated by the activation of oxytocin receptors in the mouse myometrium. A reverse transcription polymerase chain reaction study failed to reveal mRNA of the vasopressin V(1a) receptor in the mouse myometrium. In contrast, in the non-pregnant human myometrium, vasopressin-induced contraction was inhibited by SR49059. Oxytocin showed no effect on the myometrium. These results suggest that there are significant differences in the functional receptors and contractile responses to vasopressin and oxytocin in the human and mouse uteri.
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PMID:Vasopressin-induced contraction of uterus is mediated solely by the oxytocin receptor in mice, but not in humans. 1287 58

Vasopressin receptor subtype(s) responsible for stimulation of insulin release from pancreatic beta cells were investigated by using subtype-selective antagonists and mice that were genetically lacking either V1a or V1b receptors. Arginine vasopressin (AVP) increased insulin release from isolated mouse islet cells in a concentration-dependent manner, with a submaximal response at 100 nM. Reverse transcription-polymerase chain reaction (RT-PCR) analysis detected V1b and oxytocin, but not V1a or V2, receptor transcripts in mouse islet cells. We characterized the recently synthesized vasopressin receptor subtype antagonists (2S)1-[(2R 3S)-(5-chloro-3-(2-chlorophenyl)-1-(3,4-dimethoxybenzene-sulfonyl)-3-hydroxy-2,3-difydro-1H-indole-2-carbonyl)-pyrrolidine-2-carboxamide] (SR49059), 1-[1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl]-3,4-dihydro-2(1H)-quinolinone (OPC-21268), and (2S,4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxy-phenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2-pyrrolidine carboxamide (SSR149415) using human embryonic kidney 293 cells stably expressing the three cloned mouse vasopressin receptors (V1a, V1b, and V2). A radioligand binding study showed that SR49059 and OPC-21268 potently inhibited [3H]AVP binding to the cloned mouse V1a receptor, with Ki values of 27 and 510 nM, respectively, whereas SSR149415 potently inhibited [3H]AVP binding to the cloned mouse V1b receptor with a Ki value of 110 nM. The inhibitory effects of vasopressin antagonists on AVP-induced insulin release correlate well with the rank order of potency to inhibit [3H]AVP binding to the V1b receptor; pancreatic islet cells were significantly inhibited by SSR149415 but not by SR49059 or OPC-21268. Furthermore, the AVP effect on insulin release was entirely lost in mice lacking the V1b receptor but was preserved in mice lacking the V1a receptor. Our study, which combined pharmacological and knockout approaches, clearly demonstrates that vasopressin-stimulated insulin release from islet cells is mediated via V1b receptors.
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PMID:Vasopressin stimulates insulin release from islet cells through V1b receptors: a combined pharmacological/knockout approach. 1497 40

Whereas arginine vasopressin binds to its receptor subtypes V(1)R and V(2)R with equal affinity of approximately 2 nM, nonpeptide antagonists interact differently with vasopressin receptor subtypes. The V(2)R antagonist binding site was mapped by site-directed mutagenesis at six selected amino acid positions, K100D, A110W, M120V, L175Y, R202S, and F307I, predicted to be involved in antagonist binding differences between V(2) R and V(1)R. These mutations did not alter the affinity for arginine vasopressin. However, the affinity for six nonpeptide receptor antagonists SR121463B [1-[4-(N-tert-butylcarbamoyl)-2-methoxybenzenesulfonyl]-5-ethoxy-3-spiro-[4[(2 morpholinoethoxy)cy-clohexane]indoline-2-one, phosphate monohydrate cis-isomer], SR49059 [(2S)1-[(2R3S)-(5-chloro-3-(2 chlorophenyl)-1-(3,4-dimethoxybenzene-sulfonyl)-3-hydroxy-2,3-dihydro-1H-indole-2-carbonyl]-pyrrolidine-2-carboxamide], SSR149415 [(2S,4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2pyrrolidine carboxamide, isomer(-)], OPC21268 [1-[1-[4-(3-acetylaminopropoxy)benzoyl]-4-piperidyl]-3,4-dihydro-2(1H)-quinolinone], OPC41061 [(+/-)-4'-[(7-chloro-2,3,4,5-tetrahydro-5-hydroxy-1H-1-benzazepin-1-yl)carbonyl]-o-tolu-m-toluidide], and OPC31260, [(+/-)-5-dimethylamino-1-[4-(2-methylbenzoylamino)benzoyl]-1,2, 3,4,5-tetrahydro-1H-benzazepine monohydrochloride], was altered to varying degrees, resulting in differences up to 6000-fold. Replacement of the small alanine for the bulky tryptophan in position 110 resulted in a reduced affinity for all six antagonists. In contrast, replacement of the large methionine for the smaller valine in position 120 caused a dramatic increase in affinity, up to a K(i) of 7 fM for OPC31260. Molecular modeling revealed that the binding sites for arginine vasopressin and the nonpeptide antagonists are partially overlapping. Whereas arginine vasopressin binds on the extracellular surface of V(2) R, the nonpeptide antagonists penetrate deeper into the transmembrane region of the receptor, in particular OPC21268. The mutagenesis data point to significant differences in the shape of the V(1)R and V(2)R antagonist binding pockets. The most important factor determining the specificity of nonpeptide antagonists seems to be the shape of the binding pocket on the receptor.
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PMID:Mapping the binding site of six nonpeptide antagonists to the human V2-renal vasopressin receptor. 1623 9


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