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)

To assess sites and mechanism of action of prostaglandin E2 (PGE2) on water permeability (PF), we determined PGE2 effects on antidiuretic hormone (ADH)- and adenosine 3',5'-cyclic monophosphate (cAMP)-stimulated PF in rat terminal inner medullary collecting ducts perfused in vitro. PGE2 (10(-7) M) reversibly inhibited ADH-stimulated PF (1.131 +/- 192 to 532 +/- 208 microns/s). In contrast to that observed in rabbit, PGE2 also inhibited an established PF response to the exogenous cAMP analogue 8-p-(chlorophenylthio)-cAMP (696 +/- 107 to 399 +/- 99 microns/s). PGE2 alone had no effect on PF. The protein kinase C inhibitor staurosporine (10(-8) M) blocked PGE2-mediated inhibition of cAMP-stimulated PF. PGE2 caused a rapid spikelike increase in intracellular calcium [( Ca2+]i) followed by a stable elevation above basal values. Only the latter effect was abolished in a zero calcium bath. Neither staurosporine nor cAMP altered the [Ca2+]i response. These studies are the first to demonstrate PGE2-mediated inhibition of an established PF response to cAMP independent of changes in intracellular cAMP. The pattern of [Ca2+]i release and sensitivity to staurosporine suggests that this effect is mediated via signaling through phospholipase C. The results underscore the importance of species differences, axial heterogeneity, and/or in vivo conditioning for functional expression of cellular signaling pathways.
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PMID:PGE2 inhibits water permeability at a post-cAMP site in rat terminal inner medullary collecting duct. 131 24

The kinetics of vasopressin-stimulated PtdIns(4,5)P2 and phosphatidylcholine (PtdCho) hydrolysis in relation to sustained diacylglycerol (DAG) formation was investigated in A10 vascular-smooth-muscle cells in culture. Vasopressin stimulated a transient increase in Ins(1,4,5)P3 mass formation, which was mirrored by a decrease in PtdIns(4,5)P2 mass levels. Vasopressin stimulated sustained accumulation of total [3H]inositol phosphates ([3H]IP) in the presence of Li+; however, this was significantly decreased by adding a vasopressin-receptor antagonist at different times after initial stimulation. Vasopressin-stimulated phospholipase D (PLD) activity was found to be a transient phenomenon lasting approx. 2 min. Experiments involving agonist preincubation with subsequent addition of butanol confirmed that vasopressin-stimulated PLD activity was desensitized. Vasopressin stimulated an increase in formation of choline, but not of phosphocholine, suggesting that PLD was the major catalytic route of PtdCho hydrolysis in this cell line. The roles of choline and inositol phospholipid hydrolysis in the prolonged phase of DAG formation was examined by comparing vasopressin-stimulated changes in DAG levels in the presence of butanol, the protein kinase C inhibitor Ro-31-8220 or a V1a-receptor antagonist. Vasopressin-stimulated DAG formation was decreased by 40-50% in the presence of butanol between 1 and 10 min; however, during more prolonged stimulation butanol was without significant effect. In cells pretreated with Ro-31-8220, vasopressin-stimulated DAG formation was decreased by approx. 30% at 2 min, but was significantly potentiated at later times. This coincided with an enhancement of vasopressin-stimulated [3H]IP accumulation. In cells exposed to the V1a-receptor antagonist 5 min after addition of vasopressin, subsequent DAG formation was significantly decreased, indicating that sustained formation of DAG, like [3H]IP accumulation, was dependent on continual agonist receptor activation. The results are discussed in terms of different phospholipid-hydrolytic pathways providing DAG generation.
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PMID:Rapid desensitization of vasopressin-stimulated phosphatidylinositol 4,5-bisphosphate and phosphatidylcholine hydrolysis questions the role of these pathways in sustained diacylglycerol formation in A10 vascular-smooth-muscle cells. 132 72

The effects of increases in cytosolic Ca2+ on hepatocyte bile secretion are unknown. A number of agents that alter levels of cytosolic Ca2+ in the hepatocyte also produce hepatic vasoconstriction and activate protein kinase C, which complicates interpretations of their effects on bile secretion. To better understand the role of cytosolic Ca2+ in bile secretion, we examined the effect of the Ca2+ ionophore A23187 (0.1 mumol/L), the Ca2+ agonist vasopressin (10 nmol/L) and the Ca(2+)-mobilizing agent, 2,5-di(tert-butyl)-1,4-benzohydroquinone (25 mumol/L) on cytosolic Ca2+ in isolated hepatocytes and on bile flow in the isolated perfused rat liver, using vasodilators and inhibitors of protein kinase C and Ca2+ influx. Single-pass perfused livers were used, and cytosolic Ca2+ was measured by luminescent photometry in isolated hepatocytes loaded with the Ca(2+)-sensitive photoprotein aequorin. After A23187 perfusion, a sustained 74% +/- 10% (mean +/- S.D.) decrease in bile flow and a sustained 271% +/- 50% increase in perfusion pressure was observed. Simultaneous pretreatment with the vasodilator papaverine (25 mumol/L) and the protein kinase C inhibitor H-7 (50 mumol/L) abolished the pressure increase but not the decrease in bile flow, whereas pretreatment with Ni2+ (25 mumol/L) to block the influx of extracellular Ca2+ markedly reduced both the pressure increase and the decrease in bile flow. Vasopressin produced a transient (mean = 6 min) 75% +/- 4% decrease in bile flow and a sustained 7% +/- 4% increase in perfusion pressure. Pretreatment with H-7 alone corrected the vasopressin-induced pressure increase but also failed to eliminate the decrease in bile flow, whereas pretreatment with Ni2+ decreased the magnitude of the decrease by two-thirds without affecting the increase in perfusion pressure, 2,5'-di(tert-butyl)-1,4-benzohydroquinone produced a transient 65% +/- 20% decrease in bile flow and a transient 56% +/- 15% increase in perfusion pressure. In isolated hepatocytes, bromo-A23187, the nonfluorescent form of the ionophore, produced a sustained 56% +/- 32% increase in the cytosolic Ca2+ signal, whereas vasopressin resulted in a transient 241% +/- 75% increase and 2,5-di(tert-butyl)-1,4-benzohydroquinone resulted in a sustained 149% +/- 66% increase. The ionophore-induced increase in Ca2+ was abolished completely by pretreatment of the hepatocytes with Ni2+, whereas the vasopressin-induced increase was reduced by 38%.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of Ca2+ agonists on cytosolic Ca2+ in isolated hepatocytes and on bile secretion in the isolated perfused rat liver. 172 85

The effect of ethanol on receptor-mediated phospholipase C-linked signal transduction processes was investigated in isolated rat hepatocytes. Pretreatment of the cells with ethanol (6-300 mM) markedly inhibited a subsequent stimulation of phospholipase C by vasopressin, angiotensin II, or epidermal growth factor. By contrast, the effects of the alpha 1-adrenergic agonist phenylephrine and of glucagon were not affected by ethanol pretreatment. Ethanol inhibited the agonist-induced decrease in polyphosphoinositides, the formation of inositol phosphates, and the increase in cytosolic free Ca2+ levels, as detected with the intracellular Ca2+ indicator indo-1. The effects of ethanol were concentration dependent and were pronounced at low concentrations of agonists but were not significant at saturating levels. Pretreatment of the cells with the protein kinase C inhibitor H7 partly prevented the inhibition by ethanol of vasopressin-induced phospholipase C activation. By contrast, pretreatment of the cells with (Rp)-adenosine cyclic 3':5'-phosphorothioate [Rp)-cAMP-S), a competitive inhibitor of protein kinase A, potentiated the inhibitory effect of ethanol on the Ca2+ mobilization by vasopressin. (Rp)-cAMP-S similarly potentiated the inhibition of phospholipase C by the protein kinase C-activating phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA). The kinase A inhibitor also made the Ca2+ mobilization by phenylephrine sensitive to ethanol, indicating that the formation of cAMP in the cells played a role in suppressing the sensitivity to ethanol. Pretreatment of the cells with ethanol enhanced the inhibitory effects of TPA on the vasopressin-induced phospholipase C activation at all concentrations of the hormone; however, these synergistic effects were prevented when TPA was added prior to ethanol, a condition that prevents the activation of phospholipase C by ethanol. The data indicate that ethanol causes desensitization of the receptor-mediated phospholipase C secondary to the ethanol-induced activation of phospholipase C and activation of protein kinase C. Ethanol treatment also affects the sensitivity of the phospholipase C system to control by protein kinases A and C. The data indicate that ethanol can affect the control of intracellular signal transduction processes in liver cells under physiologically relevant conditions.
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PMID:Ethanol causes desensitization of receptor-mediated phospholipase C activation in isolated hepatocytes. 184 16

We have examined the effect of bradykinin (BK) and other peptide mediators with related cellular actions on tyrosine phosphorylation in confluent Swiss 3T3 fibroblast cells using an anti-phosphotyrosine antibody. Immunoblots of extracts from cells stimulated with BK showed a major heterogeneous band centered at Mr 120,000. Three phosphorylated protein species were present within this band. The lower of these three phosphoproteins was occasionally present under basal conditions. The detection of this group of phosphoproteins by the antibody was prevented by coincubation with an excess of phosphotyrosine but not with an excess of phosphoserine or phosphothreonine. The BK-promoted increase in phosphorylation was rapid and transient with the peak response apparent following BK exposure for 1 min. The response was dose-dependent with half-maximal effect occurring at 10-30 nM BK. The antagonist Arg0, Hyp3, Thi5,8, D-Phe7-BK completely inhibited the response indicating that BK was acting via a B2 kinin receptor. Bombesin, at 0.1 microM, stimulated an increase in phosphorylation of the 120-kDa group of proteins with the same efficacy as 0.1 microM BK. On the other hand, 1 microM vasopressin was considerably less efficaceous than either of the former agonists. Short-term preexposure to 0.1 microM 12-O-tetradecanoyl-phorbol-13-acetate (1 min), a protein kinase C stimulator, or 30 microM H7 (15 min), a protein kinase C inhibitor, had no significant effect either on the basal or BK-promoted increase in tyrosine phosphorylation of these proteins. BK also stimulated inositol phosphate formation in these cells. Genistein, a tyrosine kinase inhibitor, inhibited BK stimulation of tyrosine phosphorylation. In addition, genistein partially inhibited BK stimulation of inositol phosphate formation. These results show that an increase in tyrosine phosphorylation of a 120-kDa group of proteins is an early protein kinase C-independent cellular signal elicited by both bradykinin and bombesin.
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PMID:Bradykinin and bombesin rapidly stimulate tyrosine phosphorylation of a 120-kDa group of proteins in Swiss 3T3 cells. 201 98

Cultured fibroblasts (REF52 cells) were employed to investigate phospholipid degradation in response to vasopressin (VP) treatment. There have been few studies in fibroblasts which characterize the pattern and relationship of phosphatidylinositol 4,5-bisphosphate (PIP2) and non-phosphoinositide hydrolysis elicited by VP. Here we demonstrate that VP-induced PIP2 hydrolysis is closely accompanied by phosphatidylcholine (PC) degradation by phospholipase D. Cells prelabeled with [3H]arachidonic acid showed rapid formation and diminution of [3H]diacylglycerol (DG) (5-15s) when treated with VP; this was accompanied by a reduction in polyphosphoinositide radioactivity. Radiolabeled inositol trisphosphate was generated with a similar time frame. In cells prelabeled with [3H]myristic acid, which is predominantly incorporated into cellular PC, VP elicited the generation of [3H]myristoyl phosphatidate (PA) as early as 15 s, in the absence of an increase in labeled DG. In the presence of ethanol the pattern of [3H]myristoyl phosphatidylethanol (PEt) formation coincided with [3H]myristoyl-PA formation in the absence of ethanol. PEt was similarly formed, in response to VP treatment, in cells prelabeled with 1-O-[3H]hexadecyl-2-lyso-sn-glycero-3-phosphocholine. The formation of PC-derived [3H]myristoyl-DG was characterized by a lag period of approximately 1 min, after which DG increased steadily over a 10-min period. Biphasic formation of DG was observed in cells prelabeled with [3H]arachidonic acid, and the formation of [3H]PA occurred in an uninterrupted fashion. Two protein kinase C agonists, phorbol diester and dioctanoylglycerol, elicited the formation of [3H]myristoyl-PEt. The inclusion of staurosporine, a protein kinase C inhibitor, blocked VP-induced [3H]myristoyl-PEt formation by 88%. These data demonstrate that VP elicits the coordinated hydrolysis of PIP2 by phospholipase C and PC hydrolysis by phospholipase D. This event results in the prolonged generation of PA and biphasic formation of DG. From the time courses shown, we hypothesize that the early generation of PA, heretofore ascribed to products of the polyphosphoinositide cycle, are in part derived from PC by phospholipase D.
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PMID:Vasopressin-induced polyphosphoinositide and phosphatidylcholine degradation in fibroblasts. Temporal relationship for formation of phospholipase C and phospholipase D hydrolysis products. 217 Mar 80

The current study examined the effect of vasopressin on the secretion of phosphatidylcholine, the principal component of pulmonary surfactant, from adult rat alveolar type II pneumocytes in primary culture. Vasopressin stimulated secretion in a time- and dose-dependent manner. At a concentration of 10 nM, vasopressin stimulated release by 6-fold over the basal secretory rate. The concentration producing half the maximal response for vasopressin-induced secretion was 0.4 nM. The stimulation of phosphatidylcholine release by vasopressin was duplicated by the vasopressin fragment, amino acids 4 through 9. [Lys8]vasopressin and the selective vasopressin-2 agonist [deamino-8-D-Arg]vasopressin did not stimulate surfactant secretion effectively. The vasopressin- and fragment-induced secretion was inhibited by the vasopressin-1 receptor antagonist d(CH2)5TDAVP and the protein kinase C inhibitor, tetracaine, but not by the beta-adrenergic antagonist alprenolol. Vasopressin did not activate adenylate cyclase, which suggests that stimulation by vasopressin was independent of cyclic AMP. When vasopressin and isoproterenol were added concomitantly, the effects on phosphatidylcholine secretion were additive. This suggests that these two secretagogues operate via separate mechanisms.
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PMID:Stimulation of surfactant secretion by vasopressin in primary cultures of adult rat type II pneumocytes. 291 96

To evaluate a possible modulation by protein kinase C of hormonal, cAMP-mediated effects on renal epithelial cells, we studied the effect of protein kinase C activators and of bradykinin on intracellular cAMP accumulation in MDCK cells. A 15-min pretreatment of cells with phorbol 12-myristate 13-acetate or 1-oleoyl-2-acetylglycerol induced a dose-dependent inhibition of vasopressin-stimulated cAMP synthesis, but not of basal or glucagon-, prostaglandin E2-, and forskolin-stimulated cAMP generation. 4 alpha-Phorbol 12,13-didecanoate, inactive on protein kinase C, did not affect cAMP accumulation. Bradykinin (0.1-10 microM) also inhibited the stimulatory effect of vasopressin on cAMP synthesis in a concentration-dependent manner, but affected neither basal cAMP content, nor its stimulation by glucagon, prostaglandin E2 and forskolin. The effect of activators of protein kinase C and of bradykinin occurred while renal prostaglandin synthesis was blocked with indomethacin. The inhibitory effect of protein kinase C activators and bradykinin on cAMP generation was reversed by the protein kinase C inhibitor H7, was enhanced by monensin, one effect of which is to block the recycling of membrane receptors, and persisted when the GTP-binding protein N1 was blocked with 1 mM Mn2+. Our data suggest that: protein kinase C can modulate the tubular effects of vasopressin by inhibiting cAMP generation; this effect is not mediated by renal prostaglandins, and might result from a direct action on the vasopressin receptor, or on its coupling with Ns; the modulation by bradykinin of vasopressin effects are likely to be exerted, at least partly, through activation of protein kinase C.
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PMID:Protein kinase C activators and bradykinin selectively inhibit vasopressin-stimulated cAMP synthesis in MDCK cells. 303 98

Vasopressin, angiotensin II, epinephrine (alpha 1-adrenergic action) and phorbol 12-myristate 13-acetate (PMA) induce increases in membrane-associated protein kinase C activity concomitant with decreases in the cytosolic activity. The data indicate that the calcium-mobilizing hormones and the active phorbol ester induce translocation from the cytosol to the plasma membrane of this protein kinase. The protein kinase C inhibitor, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, blocked the translocation to the membrane of this protein kinase induced by PMA and vasopressin.
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PMID:Phorbol esters and calcium-mobilizing hormones increase membrane-associated protein kinase C activity in rat hepatocytes. 337 82

Rat aortic smooth muscle cells produced large quantities of nitric oxide (NO) after exposure to interleukin-1 beta, and this was depressed in the presence of the protein kinase C inhibitor bisindolylmaleimide. Intracellular cAMP levels were elevated mildly in cytokine-treated smooth muscle cells, and the presence of forskolin enhanced both the cAMP levels and NO production. Inhibition of GTP:cyclohydrolase I by 2,4-diamino-6-hydroxypyrimidine attenuated NO production by interleukin-1 beta-treated cells. GTP:cyclohydrolase is the regulatory enzyme for de novo tetrahydrobiopterin synthesis, and the latter is a required cofactor for NO synthase activity. Treatment of smooth muscle cells with forskolin induced GTP:cyclohydrolase mRNA expression, and simultaneous treatment of cells with forskolin and phorbol esters elicited NO production. Angiotensin II and arginine-vasopressin, acknowledged agonists for protein kinase C, elicited production of NO by forskolin-treated smooth muscle cells. These observations confirm the importance of GTP:cyclohydrolase activity for NO production by cultured smooth muscle cells and implicate both adenylyl cyclase and protein kinase C in this process.
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PMID:Simultaneous activation of adenylyl cyclase and protein kinase C induces production of nitric oxide by vascular smooth muscle cells. 752 13


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