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)

The aim of the present study was to determine whether vasopressin affects NaCl reabsorption in the medullary thick ascending limb of the loop of Henle when administered selectively to the luminal membrane. At 5 x 10(-6) M and 10(-8) M, luminal [Arg8]vasopressin significantly inhibited Cl- transport in the in vitro microperfused rat medullary thick ascending limb by 46.4 +/- 5.9% (P < 0.01) and 32.4 +/- 2.0% (P < 0.05) respectively. The response to 10(-8) M luminal [Arg8]vasopressin was completely blocked by the vasopressin V1 receptor antagonist [beta-mercapto-beta,beta-cyclopenta-methylenepropionyl1, O-Me-Tyr2,Arg8]vasopressin (10(-6) M), and was mimicked by the vasopressin V1 receptor agonist [Phe1, Ile5, Orn8]vasopressin (10(-8) M; delta -35.0 +/- 4.5%; P < 0.05). Luminal administration of the vasopressin V2 receptor agonist [deamino-Cys1, D-Arg8]vasopressin (5 x 10(-6) M) had no effect on transport. These data suggest that luminal vasopressin can inhibit NaCl transport in the medullary thick ascending limb of the rat via vasopressin V1 receptors.
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PMID:Effect of luminal vasopressin on NaCl transport in the medullary thick ascending limb of the rat. 890 37

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

SR 121463A, a potent and selective, orally active, nonpeptide vasopressin V2 receptor antagonist, has been characterized in several in vitro and in vivo models. This compound displayed highly competitive and selective affinity for V2 receptors in rat, bovine and human kidney (0.6 < or = Ki [nM] < or = 4.1). In this latter preparation, SR 121463A potently antagonized arginine vasopressin (AVP)-stimulated adenylyl cyclase activity (Ki = 0.26+/-0.04 nM) without any intrinsic agonistic effect. In autoradiographic experiments performed in rat kidney sections, SR 121463A displaced [3H]AVP labeling especially in the medullo-papillary region and confirmed that it is a suitable tool for mapping V2 receptors. In comparison, the nonpeptide V2 antagonist, OPC-31260, showed much lower affinity for animal and human renal V2 receptors and lower efficacy to inhibit vasopressin-stimulated adenylyl cyclase (Ki in the 10 nanomolar range). Moreover, OPC-31260 exhibited a poor V2 selectivity profile and can be considered as a V2/V1a ligand. In normally hydrated conscious rats, SR 121463A induced powerful aquaresis after intravenous (0.003-0.3 mg/kg) or oral (0.03-10 mg/kg) administration. The effect was dose-dependent and lasted about 6 hours at the dose of 3 mg/kg p.o. OPC-31260 had a similar aquaretic profile but with markedly lower oral efficacy. The action of SR 121463A was purely aquaretic with no changes in urine Na+ and K+ excretions unlike that of known diuretic agents such as furosemide or hydrochlorothiazide. In addition, no antidiuretic properties have been detected with SR 121463A in vasopressin-deficient Brattleboro rats. Thus, SR 121463A is the most potent and selective, orally active V2 antagonist yet described and could be a powerful tool for exploring V2 receptors and the therapeutical usefulness of V2 blocker aquaretic agents in water-retaining diseases.
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PMID:Characterization of SR 121463A, a highly potent and selective, orally active vasopressin V2 receptor antagonist. 898 18

The V2 vasopressin receptor undergoes ligand-induced sequestration and desensitization (Birnbaumer, M., Antaramian, A., Themmen, A. P. N., and Gilbert, S. (1992) J. Biol. Chem. 267, 11783-11788). The V2 receptor expressed in transfected cells labeled with [32P] orthophosphate was phosphorylated following the addition of 100 nM arginine vasopressin (AVP). Phosphorylation was complete 5 min after addition of AVP, and was not stimulated by increased levels of Ca2+ or cAMP. The half-maximal dose of AVP that stimulated phosphorylation was 2.4 +/- 0.4 nM, similar to the receptor KD of 4. 5 +/- 0.4 nM. The role of phosphorylation on receptor desensitization was investigated by studying two vasopressin receptors 14 and 27 amino acids shorter than the wild type receptor. The missing segments were not needed for normal ligand binding or coupling to Gs, but the last 14 amino acids were required for phosphorylation. The truncated receptors exposed to 100 nM AVP were sequestered and desensitized. The R137H V2R mutant receptor that binds vasopressin with wild type-like affinity and does not couple to Gs (Rosenthal, W., Antaramian, A., Gilbert, S., and Birnbaumer, M. (1993) J. Biol. Chem. 268, 13030-13033) was phosphorylated and subjected to ligand-induced sequestration. These results established that phosphorylation is not essential for sequestration and desensitization of the V2 vasopressin receptor. Furthermore, they revealed that the conformation acquired after ligand occupancy is necessary for receptor phosphorylation and sequestration, while coupling to Gs is not.
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PMID:Phosphorylation of the V2 vasopressin receptor. 899 63

Studies were performed on the central antidiuretic actions via the tachykinin NK-3 receptor in the rat hypothalamic paraventricular nucleus (PVN). Microinjections of the selective tachykinin NK-3 receptor agonist senktide (2-200 pmol) into the PVN resulted in prolonged inhibition of urine output in water-loaded rats, its effect being dose-dependent. The antidiuretic action of senktide was blocked by pretreatment with the vasopressin V2 receptor antagonist OPC-31260 (1 mg/kg, i.v.), but not by microinjection of the angiotensin II AT-1 receptor antagonist losartan (1 nmol) into the PVN. NK-3 receptor mRNA was strongly detected in the magnocellular part of the PVN and the supraoptic nucleus (SON) of the hypothalamus as detected by in situ hybridization histochemistry. Moreover, [3H]senktide binding sites were also detected in the PVN and the SON by receptor autoradiography. These findings suggest that NK-3 receptors in the PVN may be involved in water regulation by stimulation of vasopressin secretion from the posterior pituitary gland, and that vasopressin caused water reabsorbtion via the kidney V2 receptor.
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PMID:Antidiuretic action of tachykinin NK-3 receptor in the rat paraventricular nucleus. 901 29

Strategies for developing selective water diuretic agents have involved development of kappa opioid receptor agonists and vasopressin V2 receptor antagonists; however, these two classes of compounds have not been compared directly. We have investigated the activity of three kappa receptor agonists and one nonpeptide vasopressin receptor antagonist in conscious dogs. SB 215520, SB 215519 and niravoline are selective kappa agonists with variable abilities to cause a water diuresis and ataxia in rats. When administered to conscious hydropenic dogs, the kappa agonists resulted in an increase in free water clearance; however, these effects were associated with an antinatriuresis, an increase in heart rate and, at the higher doses, central nervous system side effects. Conversely, the vasopressin receptor antagonist, OPC 31260, resulted in a significant water diuresis without any accompanying changes in sodium excretion and heart rate, and with no apparent central nervous system effects. These studies suggest that, at least in dogs, a vasopressin receptor antagonist is a more selective water diuretic than a kappa receptor agonist.
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PMID:Comparison of the water diuretic activity of kappa receptor agonists and a vasopressin receptor antagonist in dogs. 906 1

The increase in blood clotting factor VIII (antihaemophilic factor, F-VIII) and fibrinolytic activity induced by the administration of neurohypophyseal hormone analogues, was assayed in sheep. Peptides with high selectivity for vasopressin V1, V2 or myometrial oxytocin receptors in the dose range of 0.1-10 micrograms/kg body weight were investigated. The main conclusions are as follows. The time-course of the F-VIII plasma levels following the administration of the peptides was biphasic, with one surge at about 20 min, a rebound phase, and another increase with the maximum at 60-90 min. The time-course of the fibrinolytic response, expressed as biological activity of plasminogen activator in the plasma euglobulin fraction, displayed a single maximum within 60 min. The baseline responses were reached within 90-120 min. Responses were expressed as integrals of the time-concentration curves in a predetermined time range (90-120 min). F-VIII and plasminogen activator enhancing effects seemed to be tightly linked to the specific vasopressin V2 receptor activities. [Val4,D-Arg8]Vasopressin displayed higher plasminogen activator activities than the standard substance, deamino[D-Arg8]vasopressin. The vasotocin analogue [Phe2,Orn8]oxytocin, a specific vasopressin V1 receptor agonist, also displayed high antihaemophilic and fibrinolytic potencies, expressed in terms of ED50 values, but did not reach the same maximal response as vasopressin V2 receptor agonists. Oxytocin and its highly selective uterotonic analogue, [Thr4,Gly7]oxytocin, displayed low antihaemophilic, and virtually no plasminogen activating potencies. Surprisingly, vasopressin V2 and V1V2 receptor antagonists studied in our experiments showed both enhanced F-VIII and fibrinolytic responses. Dose-response curves frequently displayed a decrease of the F-VIII, and sometimes also decreased fibrinolytic responses, at higher peptide doses. Strong decreases of the packed cell volume (haematocrit) and somewhat lower decreases of the total plasma protein concentration were observed shortly after administration of the peptides.
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PMID:Effects of neurohypophyseal hormone analogues on blood clotting factor VIII and fibrinolytic activity in sheep. 912 40

1. The effects of intracerebroventricularly (i.c.v.) injected substance P (SP), neurokinin A (NKA) and [MePhe7]neurokinin B (NKB) were investigated on renal excretion of water, sodium and potassium in the conscious saline-loaded rat. The central effects of [MePhe7]NKB were characterized with selective tachykinin antagonists for NK1 (RP 67580), NK2 (SR 48968) and NK3 (R 820) receptors. 2. Whereas SP or NKA (65 or 650 pmol) failed to modify the renal responses, [MePhe7]NKB (65-6500 pmol) produced dose-dependent and long-lasting (30-45 min) decreases in renal excretion of water (maximal reduction at 65 pmol: from 66.14 +/- 7.62 to 21.07 +/- 3.79 microliters min-1), sodium (maximal reduction at 65 pmol: from 10.19 +/- 2.0 to 1.75 +/- 0.48 mumol min-1) and potassium (maximal reduction at 65 pmol: from 4.31 +/- 1.38 to 0.71 +/- 0.27 mumol min-1). While 650 pmol [MePhe7]NKB elevated urinary osmolality, neither 65 pmol nor 6.5 nmol [MePhe7]NKB altered this parameter. 3. Both the antidiuresis and antinatriuresis induced by [MePhe7]NKB (65 pmol) were significantly blocked by the prior i.c.v. injection of R 820 (1.3 nmol, 5 min earlier), although the potassium excretion was only partially reduced. However, R 820 did not affect the antidiuresis and antinatriuresis elicited by endothelin-1 (1 pmol, i.c.v.). On its own, R 820 decreased renal potassium excretion with no effect on urinary osmolality and renal excretion of water and sodium. The i.c.v. co-injection of RP 67580 and SR 48968 (6.5 nmol each, 5 min earlier) failed to modify the renal responses to [MePhe7]NKB in a similar study. 4. The central effects of [MePhe7]NKB (65 pmol) on renal excretion were blocked by the prior i.v. administration of a linear peptide vasopressin V2 receptor antagonist (50 micrograms kg-1, 5 min earlier). 5. These results suggest that the central NK3 receptor, probably located in the hypothalamus, is implicated in the renal control of water and electrolyte homeostasis through the release of vasopressin in the conscious saline-loaded rat.
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PMID:Renal effects of intracerebroventricularly injected tachykinins in the conscious saline-loaded rat: receptor characterization. 913 83

In congestive heart failure (CHF), low cardiac output decreases the fullness of the arterial circulation. This underfilling of the arterial vascular compartment unloads the baroreceptors, resulting in a sequence of events to maintain arterial circulatory integrity. Among them, the renin-angiotensin-aldosterone axis, the sympathetic nervous system, the non-osmotic release of vasopressin and the endothelins are activated to increase vascular resistance and enhance sodium and water renal retention. Simultaneously, vasodilatory and natriuretic substances such as the natriuretic peptides are activated to counterregulate these vasoconstrictors. In the initial phase of CHF, these events contribute to the cardiorenal adaptation. However, when CHF progresses, they become maladaptive and further depress vantricular performance and increase sodium and water retention. This vicious cycle of CHF provides the rationale for the use of neurohormonal antagonists in CHF. The beneficial effects of angiotensin converting enzyme inhibitors in CHF are well described. Vasopressin V1 receptor antagonists have been associated with peripheral vasodilation and improved cardiac function in some patients with CHF. In CHF animals, the vasopressin V2 receptor antagonist has been demonstrated to reverse the defect in water excretion. Bosentan, an endothelin antagonist, is associated with an increase of cardiac index in patients with CHF. A role for exogenous natriuretic peptides is also under investigation. Modulation of the neurohumoral systems associated with CHF opens a new perspective in the treatment of cardiac edema, principally by improving cardiac performance.
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PMID:Sodium and water retention in heart failure: pathogenesis and treatment. 918 6

Arginine vasopressin (AVP) is a potent vasoconstrictor that preferentially reduces renal medullary blood flow through the stimulation of the vasopressin V1a receptor (V1aR). Studies have also shown that the vasopressin V2 receptor (V2R) may modulate AVP-mediated vasoconstriction. At present, the distribution of the V1aR and V2R within the renal cortical and medullary microcirculation has not been determined. This study was designed to localize the transcriptional and translational sites of the V1aR and V2R in microdissected intrarenal vascular segments from both the cortex and medulla, specifically the interlobar, arcuate, and interlobular arteries; afferent and efferent arterioles; glomeruli; and single outer medullary vasa recta capillaries using reverse transcription-polymerase chain reaction and Western blot analyses. The results indicated that V1aR mRNA and proteins were present in the isolated cortical or medullary vasculature, but the V2R mRNA and proteins were not found. This study suggests that the vasoconstrictor action of AVP within the renal medulla is mediated through the V1aR and that the modulatory V2R-mediated vasodilation is probably through the release of paracrine hormones found within the renal interstitial or tubular cells.
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PMID:Localization of the vasopressin V1a and V2 receptors within the renal cortical and medullary circulation. 924 56


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