UNIPROT:P01185 - FACTA Search

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Query: UNIPROT:P01185 (vasopressin)
23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This paper reports the in vitro and in vivo characterisation of a nonpeptide, orally active, vasopressin V(1A) and V(2) receptor antagonist, YM087 (methyl-1,4,5,6-tetrahydroimidazo[4, 5-d][1]benzoazepine-6-carbonyl)-2-phenylbenzanilide monohydrochloride) in the rat. YM087 dose dependently displaced the vasopressin V(1A) receptor antagonist radioligand, 125I-labelled [d(CH(2))(5),sarcosine(7)]vasopressin at vasopressin V(1A) receptors in liver and kidney medulla membranes and caused a concentration dependent displacement of the vasopressin V(2) receptor antagonist radioligand [3H]desGly-NH(2)(9)[d(CH(2))(5), D-Ile(2), Ile(4)]vasopressin at vasopressin V(2) receptors in kidney medulla membranes. In vitro binding kinetic studies showed YM087 acted as a competitive antagonist at liver V(1A) and kidney V(1A) and V(2) vasopressin receptors. Oral administration of YM087 (0.1-3 mg/kg) dose dependently inhibited vasopressin binding to liver V(1A) and kidney V(1A) and V(2) vasopressin receptors over 24 h. Oral YM087 (1-3 mg/kg/day) for 7 days in normotensive rats caused a dose dependent aquaresis with no effect on systolic blood pressure. These results show that YM087 is an orally effective vasopressin V(1A) and V(2) receptor antagonist that may be useful in the treatment of conditions characterised by vasoconstriction and fluid retention such as congestive heart failure.
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PMID:In vivo and in vitro characterisation of a nonpeptide vasopressin V(1A) and V(2) receptor antagonist (YM087) in the rat. 1052 30

Parallel and antiparallel heterodimers have been synthesized that combine into a single molecule the neurohypophyseal hormone oxytocin and the potent vasopressin V(2)-antagonist d(CH(2))(5)[D-Ile(2), Ile(4)]arginine vasopressin. Solid-phase synthesis with N(alpha)-9-fluorenylmethyloxycarbonyl (Fmoc) chemistry, featuring appropriate combinations of orthogonal protecting groups for the thiols [S-(N-methyl-N-phenylcarbamoyl)sulfenyl (Snm); S-acetamidomethyl (Acm); S-triphenylmethyl (Trt)], was used to assemble the required linear nonapeptide amide monomer intermediates, which were then brought together in defined ways by solution reactions to provide the two heterodimers. The first disulfide bridge was formed by a directed approach involving attack by the free thiol of the 1-beta-mercapto-beta, beta-cyclopentamethylenepropionic acid (Pmp) residue of one monomer onto the Snm group of a cysteine residue on the other monomer; the inverse directed strategy failed due to steric hindrance. The second disulfide bridge was formed by iodine co-oxidation of Cys(Acm) residues on adjacent chains. Biological studies revealed that both the parallel and antiparallel chimeras lack pressor activity, have low uterotonic activity, and have diuretic activities comparable to that of the monomeric V(2)-antagonist. Sodium excretion depends on experimental conditions. Thus, with a 4% water load, both chimeras display effects similar to that of an equimolar mixture of oxytocin and V(2)-antagonist, i.e., lower sodium excretion than that resulting from administration of oxytocin alone but higher than that when V(2)-antagonist was administered alone. However, when no water load was used, the parallel chimera proved to be more effective in promoting sodium excretion than either oxytocin alone or an equimolar mixture of oxytocin and V(2)-antagonist.
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PMID:Chemical syntheses and biological studies on dimeric chimeras of oxytocin and the V(2)-antagonist, d(CH(2))(5)[D-Ile(2), Ile(4)]arginine vasopressin. 1058 9

The reactivity of intrarenal arteries to vasoconstrictor and vasodilator polypeptides was examined in adult stroke-prone spontaneously hypertensive rats (SHRSP). The contraction response to endothelin-1 (ET-1) was greater in SHRSP than in age-matched Wistar-Kyoto rats (WKY), and so was the pD2 estimate (8.05+/-0.03 in SHRSP, and 7.73+/-0.06 in WKY; n=5, P < 0.05). The contraction response to, and the pD2 estimate of, vasopressin were comparable in SHRSP and WKY. Neuropeptide Y did not contract the intrarenal arteries. In norepinephrine-precontracted arteries with intact endothelium, substance P and neurokinin A did not relax the arteries of either SHRSP or WKY, while calcitonin gene-related peptide (CGRP) induced a profound relaxation response. Relaxation response to CGRP was significantly greater in SHRSP than in WKY. Atrial, brain, and C-type natriuretic peptides (ANP, BNP, CNP), vasoactive intestinal polypeptide (VIP), and peptide histidine isoleucine (PHI) all caused relaxation responses, with a greater extent of relaxation to ANP, BNP, and VIP and a less extent to CNP and PHI. However, there were no significant differences in these relaxation responses between SHRSP and WKY. The current results revealed the character of heterogeneity of rat intrarenal arteries in response to vasoconstrictor and vasodilator peptides, and showed an enhanced reactivity to ET-1 and to CGRP in SHRSP.
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PMID:Reactivity of intrarenal arteries to vasoconstrictor and vasorelaxant polypeptides in adult stroke-prone spontaneously hypertensive rats. 1064 9

The effects of metabolic fragments of [Arg(8)]-vasopressin (AVP), [pGlu(4), Cyt(6)]AVP (AVP(4-9)), and desglycinamide-[pGlu(4), Cyt(6)]AVP (AVP(4-8)) on the growth of hippocampal neurons in culture were investigated in comparison with those of AVP. AVP(4-9) caused a significant increase in filopodial length following 96 h of exposure at concentrations higher than 300 nM. AVP(4-9) was more potent than AVP. AVP(4-8) also induced an increase in filopodial length, but this effect was less than that of AVP. The selective V(1) agonist [Phe(2), Ile(3), Orn(8)]-vasopressin caused a significant increase in filopodial length, whereas the selective V(2) agonist [deamino-Cys(1), D-Arg(8)]-vasopressin showed no such effect. OPC-21268, a vasopressin V(1) antagonist, blocked AVP and AVP fragment-induced increases in filopodial length. However, the V(2) antagonist OPC-31260 showed no such effect. A23187, a representative Ca ionophore, also increased filopodial length, and the A23187-induced increase in filopodial length was potentiated by AVP and AVP fragments. These results indicated that AVP(4-9) and AVP(4-8) increased filopodial length in cultured hippocampal neurons by activating V(1) receptors. Both phenomena induced by AVP(4-9) and AVP(4-8) were associated with intracellular calcium mobilization.
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PMID:Effects of metabolic fragments of [Arg(8)]-vasopressin on nerve growth in cultured hippocampal neurons. 1071 61

Previous studies have demonstrated that arginine vasopressin (AVP) produces exaggerated renal vasoconstriction in young spontaneously hypertensive rats (SHR) relative to normotensive rats. The exaggerated renal vascular reactivity does not appear to be due to a primary defect in postreceptor calcium signal transduction. Although the magnitudes of vascular responses differ, the relative proportions of calcium entry and mobilization pathways evoked by AVP in renal resistance vessels are similar in these rat strains. The purpose of the present study was to evaluate possible differences in V(1) mRNA and receptor density and affinity in preglomerular resistance vessels (<50 microm) obtained from young Wistar-Kyoto (WKY) and SHR. Quantitative RT-PCR analysis revealed twofold greater expression of the V(1a) receptor gene in preglomerular arterioles of 7-wk-old SHR compared with WKY. In vitro radiolabeled ligand binding studies were performed under equilibrium conditions on preglomerular resistance arterioles freshly isolated from kidneys of 7-wk-old rats. The results indicate that AVP receptor density (B(max)) is two to three times greater in SHR than in WKY (248 +/- 24 vs. 91 +/- 11 fmol/mg protein, P < 0.001). The affinity does not differ between strains (K(d) = 0.5 nM). Displacement studies yielded similar results for SHR and WKY. Unlabeled AVP completely displaced [(3)H]AVP binding, with an IC(50) of 2.5 x 10(-10) M. Expression of AVP receptor types in afferent arterioles was evaluated using the V(1) receptor agonist, [Phe(2), Ile(3),Org(8)]vasopressin, the V(1) receptor antagonist, [d(CH(2))(5), Tyr(Me)(2), Tyr(NH(2))(9)]Arg(8)-vasopressin, and the V(2) receptor agonist, desamino-[D-Arg(8)]vasopressin. Both the V(1) agonist and antagonist displaced up to 90% of the AVP binding with IC(50) values of 4 x 10(-8) and 8 x 10(-7) M, respectively. The V(2) receptor agonist was a weak inhibitor, displacing less than 15% of AVP binding at a high concentration of 10(-4) M. These results demonstrate that virtually all AVP receptors in the preglomerular arterioles are of the V(1) type. Collectively, our results provide evidence that the enhanced renal reactivity to AVP is mediated by a higher density of V(1) receptors associated with increased gene expression in renal resistance vessels of SHR developing genetic hypertension.
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PMID:Upregulation of V(1) receptors in renal resistance vessels of rats developing genetic hypertension. 1083 81

Neurohypophysial hormone receptors and second messengers were studied in trout (Oncorhynchus mykiss) hepatocytes. Arginine vasotocin (AVT) and isotocin (IT) elicited a concentration-dependent inhibition of cAMP accumulation in the presence of 5x10(-8) M glucagon (maximal effect for 4.5x10(-7) M and 1.4x10(-7) M, half-maximal effect for 2.1x10(-8) M and 0.7x10(-8) M, AVT and IT respectively). The effect of glucagon was inhibited up to 90% by AVT and 80% by IT. While AVT inhibited (up to 50%) the basal cAMP production, IT had no such action. Specific V(1) or V(2) analogues (with reference to vasopressin in mammals) were used for pharmacological characterization of the type of neurohypophysial hormone receptor involved in this inhibition. The V(1) agonist [Phe(2), Orn(8)]-oxytocin inhibited the glucagon-stimulated cAMP production with a maximal effect for 6x10(-7) M and a half-maximal effect for 0.9x10(-8) M concentrations of the analogue. While the V(1) agonist reduced the glucagon-stimulated cAMP level by 70%, it showed only a tendency to reduce the basal level. The V(2) agonist [deamino(1), Val(4),d -Arg(8)]-vasopressin had no effect either on basal or on glucagon-stimulated cAMP production. The V(1) antagonist [d(CH(2))(5)(1), O-Me-Tyr(2), Arg(8)]-vasopressin totally reversed the 10(-8) M AVT-induced inhibition of 5x10(-8) M glucagon-stimulated cAMP production, whereas the V(2) antagonist [d(CH(2))(5)(1),d -Ile(2), Ile(4), Arg(8), Ala(9)]-vasopressin had no such effect. In this particular case, maximal and half-maximal effects of the V(1) antagonist were obtained for 2.3x10(-6) M and 1. 2x10(-6 )M respectively. Changes in intracellular calcium content were measured using the fluorescent probe FURA-2/AM. AVT and IT elicited a concentration-dependent increase in Ca(2+) accumulation. The comparison of the effect of 10(-8) M agonists versus AVT showed the following order of potency: AVT=IT>V(1) agonist>V(2) agonist. The V(1) antagonist reversed the AVT-induced Ca(2+) accumulation whereas the V(2) antagonist had no such effect. These results are taken as evidence for the presence in trout hepatocytes of neurohypophysial hormone receptors functionally close to the V(1a)-type linked to cAMP production and Ca(2+) mobilization.
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PMID:Neurohypophysial hormone receptors and second messengers in trout hepatocytes. 1101 61

In the present study, we have examined neurochemical correlates that may be involved in the differential cardiovascular responses observed in normotensive and hypertensive rats during stress. Using a restraint stress paradigm, both normotensive Wistar Kyoto (WKY) and Spontaneously Hypertensive rats (SHR) underwent acute (1 h restraint in a perspex tube), chronic (1 h restraint for ten consecutive days) or no restraint (control) stress. Following cessation of restraint, rats were processed by incubating sections of brain stem and kidney with [125I]-HO-LVA (0.03 nM) or [125I]Sar(1)Ile(8)-AngiotensinII (0.5 nM), in the presence of PD123319 (10 microM) or losartan (10 microM), to determine the distribution and density of vasopressin V(1A), angiotensin AT(1) and AT(2) receptors, respectively. Analysis of autoradiograms indicated changes in the density of radioligand binding in acutely and chronically-stressed rats, as compared to controls. For example, V(1A) binding in the medial nucleus tractus solitarius (SolM) decreased in the WKY but increased in the SHR. AT(1) binding in SolM did not significantly change in the WKY but decreased in the SHR with repeated restraint. In kidney slices, AT(1) binding decreased with stress in the WKY (-17%) but increased in SHR (+10-15%). AT(2) binding in the kidney showed a pattern similar to that of AT(1) binding in SHR, but not WKY. Graded increases in V(1A) binding were measured in kidney medulla and cortex of both strains (+50-60% with chronic restraint). These results suggest that physiological adaptation to restraint is associated with specific changes in V(1A), AT(1) and AT(2) receptor density within brain nuclei and kidney.
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PMID:Characterisation of vasopressin V(1A), angiotensin AT(1) and AT(2) receptor distribution and density in normotensive and hypertensive rat brain stem and kidney: effects of restraint stress. 1106 99

The effects on social recognition memory of (Arg(8))-vasopressin (AVP-(1-9), [pGlu(4), Cyt(6)]AVP-(4-8) and oxytocin locally administered into the rat's septum were investigated. In the behavioural paradigm used, a juvenile intruder was presented to an adult resident male rat twice for 5 min, with an inter-exposure interval of 120 min. Peptide-free residents investigated the juvenile during the second encounter as long as during the first encounter. Intraseptal injection just after the first encounter with graded doses of (Arg(8))-vasopressin, [pGlu(4),Cyt(6)]AVP-(4-8) or oxytocin caused a decrease of social investigation, as compared to placebo treatment, indicating facilitation of social recognition. The least effective dose was 100pg, 200pg and 300pg respectively. The action of vasopressin was blocked by both d(CH(2))(5)[Tyr(Me)(2)]AVP and d(CH(2))(5)[D-Ile(2)Ile(4)]AVP, V(1) and V(2) vasopressinergic receptor antagonists, but not by desGly(NH(2))(9)-d(CH(2))(5)[Tyr(Me)(2)Thr(4)]-OVT, an oxytocinergic receptor antagonist. None of the antagonists blocked the oxytocin-facilitating action on social recognition. They also did not affect social recognition when injected alone. The effects of vasopressin seem to be mediated by vasopressinergic receptors dissimilar to those found in the periphery, while the receptors involved in the action of oxytocin remain to be elucidated.
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PMID:Neurohypophyseal hormone receptors in the septum are implicated in social recognition in the rat. 1122 37

To examine the role of vasopressin V(1) and V(2) receptors, nitric oxide and prostanoids in the cerebrovascular effects of arginine vasopressin, cerebral blood flow was electromagnetically measured in awake goats. In 16 animals, vasopressin (0.03 - 1 microg), injected into the cerebral circulation, caused increments of resting cerebrovascular resistance which ranged from 18% (0.03 microg, P<0.01) to 79% (1 microg, P<0.01). Desmopressin (0.03 - 1 microg, four goats) did not affect significantly cerebrovascular resistance. The cerebrovascular resistance increases by vasopressin were reduced significantly by the antagonist for vasopressin V(1) receptors d(CH(2))(5)Tyr(Me)-AVP in a rate depending way (five (six goats) and 15 (four goats) microg min(-1)), and by the mixed antagonist for vasopressin V(1) and V(2) receptors desGly-d(CH(2))(5)-D-Tyr(Et)Val-AVP (5 microg min(-1), four goats), and they were not significantly affected by the antagonist for vasopressin V(2) receptors d(CH(2))(5), D-Ile(2), Ile(4)-AVP (5 microg min(-1), four goats). The inhibitor of nitric oxide synthesis N(w)-nitro-L-arginine methyl ester (L-NAME, 47 mg kg(-1) i.v., five goats) augmented cerebrovascular resistance by 130% (P<0.01), and for 24 h after this treatment the cerebrovascular effects of vasopressin were potentiated. The inhibitor of cyclo-oxygenase meclofenamate (6 mg kg(-1) i.v., five goats) did not modify significantly resting haemodynamic variables measured or the cerebrovascular effects of vasopressin. Therefore, the vasopressin-induced cerebral vasoconstriction may be mediated by vasopressin V(1) receptors, without involvement of vasopressin V(2) receptors, and may be modulated by nitric oxide but not by prostanoids.
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PMID:Cerebral vasoconstriction produced by vasopressin in conscious goats: role of vasopressin V(1) and V(2) receptors and nitric oxide. 1130 56

The reduced pressure response to vasopressin during acute sepsis has directed our interest to the regulation of vasopressin V(1A) receptors. Rats were injected with lipopolysaccharide for induction of experimental gram-negative sepsis. V(1A) receptor gene expression was downregulated in the liver, lung, kidney, and heart during endotoxemia. Inasmuch as the concentrations of proinflammatory cytokines such as interleukin-1beta, tumor necrosis factor-alpha, and interferon-gamma were highly increased during sepsis, the influence of these cytokines on V(1A) receptor expression was investigated in primary cultures of hepatocytes and in the aortic vascular smooth muscle cell line A7r5. V(1A) receptor expression was downregulated by the cytokines in a nitric oxide-independent manner. Blood pressure dose-response studies after injection of endotoxin showed a diminished responsiveness to the selective V(1) receptor agonist Phe(2),Ile(3),Orn(8)-vasopressin. Our data show that sepsis causes a downregulation of V(1A) receptors and suggest that this effect is likely mediated by proinflammatory cytokines. We propose that this downregulation of V(1A) receptors contributes to the attenuated responsiveness of blood pressure in response to vasopressin and, therefore, contributes to the circulatory failure in septic shock.
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PMID:Cytokine-mediated downregulation of vasopressin V(1A) receptors during acute endotoxemia in rats. 1189

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