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)

It has been almost 40 years since the diuretic effect of alpha-adrenoceptor agonists was first demonstrated. Two possible mechanisms were proposed: inhibition of vasopressin secretion and antagonism of the cellular hydrosmotic actions of vasopressin. The debate could not be settled then for the lack of appropriate experimental models and pharmacological tools. Advances made in adrenoceptor pharmacology in the 1970s such as 1) subdivision of alpha-adrenoceptors into alpha 1- and alpha 2-subtypes; 2) development of selective agonists and antagonists; and 3) localization of both adrenoceptor subtypes in the kidney, including the proximal and collecting tubules, stimulated new research. With regard to renal adrenoceptors, selective alpha 2-agonists have been shown to induce diuresis in dogs and rats. Whereas in the dog the increase in urine flow results mostly from an increase in osmolal clearance, in the rat the diuresis results in large part from an increase in the excretion of solute-free water. In vitro studies on isolated collecting tubules from rats and rabbits (none from dogs) have shown that alpha 2-agonists inhibit vasopressin-induced adenosine 3',5'-cyclic monophosphate formation and that this effect is mediated by the inhibitory guanine nucleotide regulatory protein and abolished by pertussis toxin treatment. In vivo evidence in support of such a mechanism was presented from conscious Brattleboro homozygous rats in which a selective alpha 2-agonist inhibited the antidiuretic effect of exogenous vasopressin, and this effect was abolished by pertussis toxin. The physiological importance of renal alpha 2-adrenoceptors was identified by use of adrenal medullectomized rats and the alpha 2-antagonist, yohimbine.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Modulation of vasopressin antidiuretic action by renal alpha 2-adrenoceptors. 216 55

Desensitization of vasopressin V2 receptor-mediated adenylate cyclase was studied in canine kidney cell line, MDCK cells. Overnight treatment of MDCK cells with arginine vasopressin (AVP) resulted in a loss of vasopressin receptors and an inhibition of cAMP accumulation in response to AVP. Both the loss of receptor and reduction in cAMP accumulation were time- and AVP concentration-dependent. Desensitization was selective for AVP because cAMP formation in response to isoproterenol, prostaglandin E1 (PGE1) and forskolin was not affected by AVP pre-treatment. Pre-treatment of MDCK cells with phorbol dibutyrate (PDBu) also caused a dose-dependent inhibition of AVP mediated cAMP accumulation, but not of isoproterenol-, PGE1- and forskolin-induced cAMP accumulation. PDBu pre-treatment did not cause loss of vasopressin receptors. Instead, the affinity for vasopressin was changed by PDBu treatment. Pre-treatment of the cells with pertussis toxin (PT) had no effect on the desensitization and downregulation of vasopressin (V2) receptors, suggesting that the desensitization may not be mediated by pertussis toxin sensitive G-protein. Our data suggest that pre-treatment of MDCK cells with AVP or PDBu caused desensitization of AVP-mediated cAMP accumulation and that downregulation of V2 receptors required agonist occupancy of the receptors, whereas the affinity of the receptors was changed by phorbol ester treatment.
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PMID:Desensitization of vasopressin sensitive adenylate cyclase by vasopressin and phorbol esters. 216 86

Agonist-stimulated divalent cation entry was studied in fura-2-loaded hepatocytes. In the presence of extracellular Mn2+, the Ca2(+)-mobilizing hormone vasopressin produced a severalfold stimulation of the basal rate of fura-2 fluorescence quenching as a result of Mn2+ influx; this effect was blocked by the presence of Ni2+ in the incubation medium. Half-maximum and maximum stimulation of Mn2+ influx was observed with 0.1 and 0.8 nM vasopressin, respectively. Agonist-stimulated Mn2+ influx was also seen with angiotensin II, ATP, phenylephrine, and the combination of AlCl3 and NaF. The stimulation of Mn2+ influx did not occur immediately after addition of Ca2(+)-mobilizing agents, but was characterized by a latency period of 20-30 s. In contrast to vasopressin, glucagon did not stimulate Mn2+ influx into hepatocytes, but produced both a 3-fold enhancement of the rate of vasopressin-stimulated Mn2+ entry and the abolishment of the latency period. The effects of glucagon were mimicked by forskolin and dibutyryl cAMP. Pretreatment of hepatocytes with pertussis toxin or depolarization of the cells altered neither the basal rate of Mn2+ entry nor the ability of vasopressin to stimulate this rate. Emptying of the inositol 1,4,5-trisphosphate-sensitive Ca2+ store by treatment with 2,5-di-(tert-butyl)-1,4-benzohydroquinone (tBuBHQ) did not enhance Mn2+ entry into hepatocytes; however, exposure of the cells to tBuBHQ for 2 min markedly enhanced the ability of vasopressin, alone or in combination with glucagon, to increase the rate of Mn2+ influx. Furthermore, pretreatment with tBuBHQ for 2 min abolished the latency of vasopressin-stimulated Mn2+ influx. It is concluded that Ca2(+)-mobilizing hormones stimulate Ca2+ influx in hepatocytes, possibly through receptor-operated Ca2+ channels. The stimulation of divalent cation entry is transduced by a G protein, and the rate of influx appears to be controlled both by the intracellular level of cAMP and the empty state of an intracellular Ca2+ pool that may be inositol 1,4,5-trisphosphate-insensitive.
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PMID:Receptor-operated calcium influx in rat hepatocytes. Identification and characterization using manganese. 217 Mar 82

Quiescent cultures of Swiss 3T3 cells can be stimulated to recommence DNA synthesis by polypeptide growth factors, neuropeptides, and various pharmacologic agents that act via multiple signal transduction pathways. Neuropeptides of the bombesin family provide potent mitogens to elucidate these pathways. These peptides bind to specific receptors that have been characterized by radioligand binding and sensitivity to antagonists and identified as glycoproteins with a Mr of 75,000-85,000 by chemical cross-linking. After binding, bombesin elicits a cascade of early molecular events including stimulation of phosphorylation of the acidic Mr 80,000 cellular protein, which is a major substrate of protein kinase C; Ca2+ mobilization mediated by Ins(1,4,5)P3, Na+ and K+ fluxes, transmodulation of EGF receptor, enhancement of cAMP accumulation, and expression of the proto-oncogenes c-fos and c-myc. Studies using membrane preparations and permeabilized 3T3 cells indicate that G proteins play a role in the transduction of the mitogenic signal triggered by the binding of bombesin to its receptor. A pertussis toxin-insensitive G protein couples the bombesin receptor to the generation of a signal that activates protein kinase C, whereas a pertussis toxin-sensitive G protein mediates cross-talk between transmembrane signaling pathways. Bombesin-mediated mitogenesis can be blocked by different antagonists and by interrupting the signal-transduction process at various postreceptor levels. Thus, prolonged treatment with vasopressin causes heterologous desensitization to the mitogenic action of bombesin. This mitogenic block is mediated by uncoupling the receptor from its signaling system. Loss of responsiveness to bombesin-stimulated DNA synthesis is also induced by down-regulation of protein kinase C.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Bombesin stimulation of mitogenesis. Specific receptors, signal transduction, and early events. 217 58

Addition of vasopressin (100 nM) to rat hepatocytes prelabelled with [3H]inositol stimulated the production of inositol phosphates in the presence of 20 mM Li+. Preincubation of hepatocytes with insulin (50 nM) or glucagon (10 nM) had no significant effect alone but enhanced the effects of vasopressin after a lag period of at least 1 min. The effects of insulin and glucagon appeared additive in this respect. Insulin also enhanced the norepinephrine-mediated stimulation of inositol phosphate accumulation. The enhancement by insulin of the effects of vasopressin required at least 0.5-5 nM insulin and did not involve changes in [3H]inositol lipid labelling or IP3 phosphatase activity. The effect of insulin appeared insensitive to prior treatment of hepatocytes with pertussis toxin (200 ng/ml for 18-24 h) or cholera toxin (100 ng/ml for 3-4 h). The glucagon enhancement of the effects of vasopressin was not affected by pertussis toxin but was mimicked by cholera toxin. The response of hepatocytes to vasopressin in the absence of Li+ was smaller and more transient. Under these conditions a 5 min prior incubation with insulin inhibited the stimulation by vasopressin of inositol phosphate accumulation. A similar inhibitory effect of prior insulin exposure on the transient activation by vasopressin of exogenous phosphatidylinositol 4,5-bisphosphate breakdown by hepatocyte homogenates was also seen. These data indicate that insulin, although having no effect on basal inositol phosphate accumulation, can either enhance or antagonise the effects of vasopressin in primary rat liver hepatocyte cultures depending on the experimental conditions.
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PMID:Effects of insulin on inositol phosphate production in cultured rat hepatocytes. 218 Apr 88

The potentiation of corticotropin-releasing factor (CRF)-stimulated cAMP production by vasopressin (VP) in the pituitary cell was investigated by studies on the interaction of CRF, VP, and the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA) on cAMP, adenylate cyclase and phosphodiesterase. Addition of VP or PMA (0.01-100 nM) alone did not alter cellular cAMP content, but markedly increased the effect of 10 nM CRF with ED50 of about 1 nM. Treatment of the cells with 200 ng/ml pertussis toxin for 4 h increased CRF-stimulated cAMP accumulation by 3.2-fold, an effect that was not additive to those of VP and PMA. Incubation of pituitary cells with 2 mM 1-methyl-3-isobutylxanthine increased CRF-stimulated cAMP accumulation and decreased the relative effect of VP and PMA, suggesting that the actions of VP and PMA are partially due to inhibition of phosphodiesterase. This was confirmed by the demonstration of a 30% inhibition of the low-affinity phosphodiesterase activity in cytosol and membranes prepared from cells preincubated with VP or PMA. In intact cells, following [3H]adenine prelabeling of endogenous ATP pools, measurement of adenylate cyclase in the presence of 1-methyl-3-isobutylxanthine showed no effect of VP and PMA alone, but did show a 2-fold potentiation of the effect of CRF. Measurement of adenylate cyclase in pituitary homogenates by conversion of [alpha-32P]ATP to [32P]cAMP showed a paradoxical GTP-dependent inhibition by VP of basal and CRF-stimulated adenylate cyclase activity, suggesting that the VP receptor is coupled to an inhibitory guanyl nucleotide-binding protein. Pertussis toxin pretreatment of the cells prevented the VP inhibition of adenylate cyclase activity observed in pituitary cell homogenates. These findings indicate that besides inhibition of phosphodiesterase, VP has a dual interaction with the pituitary adenylate cyclase system; a direct inhibitory effect, manifested only in broken cells, that is mediated by a receptor-coupled guanyl nucleotide-binding protein, and a physiologically predominant indirect stimulatory effect in the intact cell, mediated by protein kinase C phosphorylation of one of the components of the CRF-activated adenylate cyclase system.
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PMID:Phorbol 12-myristate 13-acetate and vasopressin potentiate the effect of corticotropin-releasing factor on cyclic AMP production in rat anterior pituitary cells. Mechanisms of action. 243 73

We investigated the mechanism for lithium-induced inhibition of vasopressin-stimulated adensoine 3',5'-cyclic monophosphate (cAMP) production in the renal epithelial cell line LLC-PK1. In LLC-PK1 membranes lithium caused direct inhibition of hormone-stimulated adenylate cyclase activity by competing with magnesium. Fifty percent inhibition occurred at 20 mM lithium. The maximum transport activity (Vmax) but not the activation constant (Ka) for activation by vasopressin was altered. Activation by GTP and its nonhydrolyzable analogues was also inhibited by lithium. Furthermore, kinetic studies revealed that the lag phase in the activation of adenylate cyclase by 5'-guanylimi-dotriphosphate [Gpp(NH)p] was prolonged from 1 to 3 min, suggesting an effect of lithium on magnesium-dependent activation of the stimulatory GTP binding protein Gs. The function of the corresponding inhibitory GTP-binding protein Gi, as assessed by GTP inhibition of vasopressin-stimulated adenylate cyclase activity in the presence and absence of pertussis toxin pretreatment, was unaffected. Intact LLC-PK1 cells incubated in 10 mM lithium (approximate urinary concentration in lithium-treated patients) attained an intracellular lithium concentration of 17 mM, which led to a 40% reduction in cAMP formation. Magnesium loading of intact cells with the ionophore A23187 reversed the inhibitory effect of lithium. It is concluded that lithium directly inhibits the activation of vasopressin-sensitive adenylate cyclase in renal epithelia by competing with magnesium for activation of Gs. This direct effect on Gs activation accounts for the inhibitory effect of lithium on cAMP production in the intact cell.
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PMID:Mechanism of Li inhibition of vasopressin-sensitive adenylate cyclase in cultured renal epithelial cells. 246 Oct 98

To aid in characterizing adenosine receptors in renal cells, primary cultures of rabbit cortical collecting tubule (RCCT) cells were infected with an adenovirus 12-simian virus 40 hybrid, resulting in a continuous cell line. The cells, designated RCCT-28A, retained their epithelial morphology and reacted with a monoclonal antibody specific for rabbit collecting tubule. Adenosine 3',5'-cyclic monophosphate (cAMP) accumulation was stimulated by vasopressin (AVP), isoproterenol, prostaglandin E2 (PGE2), calcitonin, parathyroid hormone, and a potent adenosine A1- and A2-receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA). A more selective adenosine A1-receptor agonist, N6-cyclohexyl adenosine (CHA) inhibited basal and AVP-stimulated cAMP accumulation. Cytosolic free calcium was transiently elevated by bradykinin, PGE2, NECA, and CHA. To examine the mechanism by which adenosine analogues increase intracellular free calcium, phosphoinositide (PI) turnover was assessed in the 28A cells after labeling with myo-[3H]inositol. NECA and CHA increased [3H]inositol phosphate formation with an approximate half-maximal effective concentration of 0.1 microM for both analogues. The increase in PI turnover was blocked by the selective adenosine A1-receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine and pretreatment of the 28A cells with pertussis toxin. These results suggest that adenosine analogues increase cytosolic free calcium by stimulating PI turnover.
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PMID:Adenosine-sensitive phosphoinositide turnover in a newly established renal cell line. 247 75

Vasopressin (V2) receptors were solubilized from porcine kidney membranes with the detergent egg lysolecithin. Binding of [3H]vasopressin to the solubilized fraction was rapid, specific, and saturable. The agonist dissociation constants observed in membranes and solubilized fractions were 1.7 +/- 0.3 and 2.3 +/- 0.2 nM, respectively. In competition binding experiments, the solubilized fraction exhibited the same pharmacological profile as the membranes. Chemical crosslinking of [125I]vasopressin to the solubilized fraction followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis demonstrated a 62-kDa band which was specifically labeled with [125I]vasopressin. Vasopressin binding sites from the solubilized fractions were resolved by gel filtration and ultracentrifugation on a sucrose gradient. In addition, agonist high affinity binding to V2 receptors and its sensitivity to guanine nucleotides were preserved even after solubilization in the absence of prebound agonist prior to solubilization. Addition of guanine nucleotides such as GTP gamma S decreased the specific binding of [3H]arginine vasopressin to these solubilized fractions in a dose-dependent manner, suggesting the solubilization of a V2 receptor-G protein complex. [32P]ADP ribosylation of the solubilized fraction by cholera and pertussis toxins revealed specifically labeled proteins with molecular weights of 42,000-43,000 and 39,000-41,000, respectively, on sodium dodecyl sulfate polyacrylamide gels. Furthermore [35S]GTP gamma S binding to these solubilized fractions was enhanced by vasopressin, confirming that a significant proportion of the vasopressin receptors must be closely coupled to G proteins even when these receptors are solubilized in the absence of agonist. These results are in contrast with those reported for beta, alpha 2 adrenergic and D2 dopaminergic receptor systems, but in agreement with D1 dopaminergic and A1 adenosine receptors. The molecular mechanism responsible for this difference remains to be determined.
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PMID:Solubilization of a guanine nucleotide-sensitive form of vasopressin V2 receptors from porcine kidney. 252 56

Guanine nucleotides and pertussis toxin were used to test for the involvement of a guanine nucleotide binding protein in the vasopressin V1 receptor-mediated stimulation of protein kinase C activity in Swiss 3T3 cells. Addition of vasopressin in the presence of [gamma-32P]ATP and digitonin caused a marked and rapid increase (8 +/- 1-fold after 1 min) in the phosphorylation of an Mr = 80,000 cellular protein (80K), a specific marker for protein kinase C activation. This phosphorylation was selectively blocked by the V1 receptor antagonist Pmp1-0-Me-Tyr2 [Arg8] vasopressin, indicating that the effect was mediated through the vasopressin V1 receptor. Down regulation of protein kinase C by prior prolonged pretreatment of intact cells with phorbol 12,13-dibutyrate (PBt2) blocked the ability of vasopressin to stimulate the phosphorylation of 80K in digitonin-permeabilized cells. Addition of a submaximal concentration of vasopressin together with the GTP analogue GTP-gamma-S caused a synergistic stimulation of 80K phosphorylation. The GDP analogue GDP-beta-S caused a 50% inhibition of the phosphorylation of 80K induced by a saturating concentration of vasopressin and shifted the vasopressin dose-response curve to the right. GDP-beta-S had no effect on the dose-response for the stimulation of 80K phosphorylation induced by PBt2. Prior incubation of intact quiescent cultures of Swiss 3T3 cells with pertussis toxin did not impair either vasopressin-induced increase in cytosolic [Ca2+] or activation of protein kinase C. These findings provide functional evidence for the involvement of a pertussis toxin-insesitive G protein in the vasopressin V1 receptor-mediated stimulation of protein kinase C in Swiss 3T3 cells.
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PMID:Vasopressin rapidly stimulates protein kinase C in digitonin-permeabilized Swiss 3T3 cells: involvement of a pertussis toxin-insensitive guanine nucleotide binding protein. 253 Feb 40

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