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)

The phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate) stimulates baseline Na+ transport across frog skin epithelium and partially inhibits the natriferic response to vasopressin. The effects are produced largely or solely when TPA is added to the mucosal surface of the tissue. Although TPA activates protein kinase C, it has other effects, as well. Thus, the biochemical basis for the effects and the ionic events involved have been unclear. Furthermore, the physiologic implications have been obscure because of the sidedness of TPA's actions. We now report that two synthetic diacylglycerols (DAG) replicate the stimulatory and inhibitory effects of TPA on frog skin. DAG is the physiologic activator of PKC. In this tissue, it produces half-maximal stimulation at a concentration of less than or equal to 19 microM. In contrast to TPA, DAG is about equally effective from either tissue surface. In a series of eight experiments, DAG was found to depolarize the apical membrane. Diacylglycerol also increases the paracellular conductance of frog skins bathed with mucosal Cl- Ringer's solution. The latter effect can be minimized by replacing NO3- for Cl- in the mucosal solution. Under these conditions, combined intracellular and transepithelial measurements indicated that DAG increased both the apical Na+ permeability and intracellular Na+ concentration. These results are qualitatively similar to the effects of cyclic 3',5'-AMP on this tissue, suggesting that activation of PKC by DAG causes phosphorylation of the same or nearby gating sites phosphorylated by cAMP. We propose that apical Na+ entry is regulated in part by activation of PKC, and that insulin may be a physiologic trigger of this activation.
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PMID:Diacylglycerols stimulate short-circuit current across frog skin by increasing apical Na+ permeability. 349 45

Cross-talk between signaling pathways is increasingly recognized as integral to cellular function. We investigated whether the mitogen-activated protein kinase (MAPK) pathway alters vasopressin (AVP) stimulation of protein kinase A (PKA) by specifically studying the role of Ras. Mouse cortical collecting duct cells (M-1) were transfected with a cDNA encoding oncogenic Ras. Transfection was confirmed by Western blot analysis and functionally by enhanced basal MAPK activity. When compared with basal MAPK activity of 26.4 +/- 6.6 pmol/mg/min in controls, basal MAPK activity varied widely in Ras-transfected clones from 29.0 +/- 6.6 to 96.6 +/- 13.4 pmol/mg/min. Clones that functionally expressed activated Ras displayed complete abolition of AVP-stimulated PKA activity, whereas those that failed to express elevated basal MAPK activity showed intact AVP-stimulated PKA. The correlation between expression of high basal MAPK activity and inhibition of AVP-induced PKA yielded a correlation coefficient of -0.92 (P = 0.009). Exposure to 10 microM forskolin or 1 microgram/ml cholera toxin resulted in comparable activation of PKA in all clones. We found no correlation between PKC activity of the clones and PKA inhibition. To assess whether the observed effect was due to one known Ras target, cells were transfected with constitutively activated Raf. M-1 cells expressing activated Raf exhibited elevated MAPK activity. The Raf clones showed no impairment of AVP-stimulated PKA activity. We conclude that expression of activated Ras is inhibitory of AVP-induced PKA activation in the M-1 cortical collecting duct cell line at a site proximal to G alpha s protein. The failure of Raf to influence AVP signaling indicates that the action of Ras is through a pathway independent of this Ras target.
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PMID:Expression of GTPase-deficient Ras inhibits vasopressin signaling in cultured cortical collecting duct cells. 761 32

Studies were performed to determine the primary signal transduction mechanism that mediates adenosine stimulation of electrogenic sodium transport in renal epithelial cells. Experiments were performed on cultured amphibian A6 cells with an adenosine analogue that preferentially binds to the A1 receptor, cyclohexyladenosine (CHA). Sodium transport was assessed by the equivalent short circuit current (Ieq). CHA was found to stimulate Ieq via activation of an A1 receptor because (1) the threshold concentration was 1 nM compared to that of 10 microM for the specific A2 agonist CGS21680, (2) CHA inhibited vasopressin (AVP)-stimulated cAMP production by a pertussis toxin-sensitive mechanism, and (3) the action of CHA was inhibited by the A1 antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). CHA increased intracellular Ca2+ ([Ca2+]i) and stimulated phosphoinositide turnover at concentrations that increased Ieq and in a time course that paralleled the increase in Ieq. Ion transport was stimulated by a Ca(2+)-dependent mechanism because the CHA induced increase in Ieq was inhibited by chelating [Ca2+]i with 5,5'dimethyl BAPTA in a dose-dependent manner, with a Ki of approximately 10 microM. The increase in Ieq was also dose-dependently inhibited by the specific PKC inhibitors dihydroxychlorpromazine and chelerythrine, and by trifluoperazine which inhibits PKC and calmodulin. Further studies indicated that CHA-stimulated Ieq was independent of cAMP generation because CHA did not induce an increase in cAMP accumulation parallel to the increase in Ieq in a dose-response analysis, and the adenylate cyclase inhibitor 2',5' dideoxy-adenosine (DDA) did not affect the CHA-induced increase in Ieq.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adenosine stimulation of Na+ transport is mediated by an A1 receptor and a [Ca2+]i-dependent mechanism. 764 26

We have documented new observations with respect to PGE2 action in the rabbit CCD. (1) PGE2 can inhibit both cAMP and vasopressin-induced water flow, depending on the sequence of PGE2 addition with respect to vasopressin or cAMP. (2) PGE2 inhibition of vasopressin or cAMP-stimulated water flow can be reversed with staurosporine. Thus, PGE2 inhibits vasopressin-stimulated water flow by activation of PKC and (3) PGE2 induces release of calcium from intracellular stores. These results strongly suggest the presence of a PGE2 receptor coupled to PIP2 hydrolysis. PGE2 mediated increases in cytosolic calcium are responsible for the inhibitory action of PGE2 on sodium transport. While stimulation of cAMP production by PGE2 may contribute to the inhibition of sodium transport, it is not required since in the presence of 8-CPTcAMP, PGE2 still decreases sodium transport. The effect of PGE2 on sodium transport is pertussis toxin insensitive and is unlikely to be mediated by an inhibitory G protein. Using PGE2 and one of its selective analogues, sulprostone, we have provided evidence for functionally distinct PGE2 receptors. Separate PGE2 receptor subtypes appear to be coupled to separate transport processes. These receptor subtypes may correspond to the EP1, EP2 and EP3 receptors described earlier in smooth muscle. Thus, an EP2 like receptor stimulates cAMP generation and water reabsorption while an EP1 like receptor increases [Ca++]i and inhibits sodium reabsorption. Finally, an EP3 receptor, equivalently activated by sulprostone and PGE2, may couple to Gi and mediate pertussis toxin sensitive inhibition of vasopressin-stimulated water flow.
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PMID:Cellular signalling of PGE2 and its selective receptor analogue sulprostone in rabbit cortical collecting duct. 782 28

Studies were performed to determine the signal transduction mechanism involved in the onset of insulin stimulated electrogenic sodium transport (Ieq) in cultured A6 cells. Insulin stimulated Ieq at a threshold concentration of one nM and a half-maximum concentration of approximately 3 nM. The onset of action occurred within 10 seconds and the increase in Ieq was augmented by pretreatment with aldosterone, similar to the action of vasopressin. Insulin stimulated an increase in Ca2+i in a dose-dependent manner that involved release from intracellular stores. Hormone stimulated Ieq was dependent on increases in Ca2+i because pretreatment with 5, 5' dimethyl BAPTA/AM blocked the increase in sodium transport. Further studies with dihydroxyclorpromazine, trifluoperazine and genistein, inhibitors of PKC, Ca2+i dependent, calmodulin dependent kinases and tyrosine kinase, respectively, suggested that the action of insulin was dependent on activation of these kinases. In contrast, insulin stimulated Ieq was independent of changes in cAMP, because insulin did not increase the accumulation of cAMP, and inhibition of adenylate cyclase with 2', 5' dideoxyadenosine did not affect transport. These results suggest that insulin, as previously shown for aldosterone, activates apical membrane amiloride sensitive sodium channels by a calcium-dependent second messenger system.
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PMID:Mechanism of insulin-stimulated electrogenic sodium transport. 799 87

Teleocidin, a phorbol ester-type tumor promoter, inhibits cell proliferation and calcium mobilization induced by epidermal growth factor and vasopressin in PLC/PRF/5 hepatoma cells. These inhibitory effects of teleocidin were observed even after a prolonged exposure of the hepatoma cells to this promoter, suggesting the presence of down-regulation-resistant protein kinase C in this hepatoma cell line. Column chromatography of cytosolic fractions showed three separate peaks of protein kinase C activity, two being down-regulation-sensitive while one was down-regulation-resistant. This down-regulation-resistant PKC is suggested to be responsible for the inhibitory effect of teleocidin on cell proliferation and calcium mobilization induced by epidermal growth factor and vasopressin.
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PMID:Involvement of down-regulation-resistant protein kinase C in teleocidin inhibition of cell proliferation and calcium mobilization induced by epidermal growth factor and vasopressin in human hepatoma cells. 839 71

Treatment of rat 3Y1 fibroblasts with vasopressin (AVP) results in a transient activation of MAP kinase as potent as with EGF and serum. An antagonist of vasopressin receptor V1, but not an antagonist of V2, inhibited the AVP-induced activation of MAP kinases, indicating that AVP activates MAP kinases through V1 receptor. Prolonged TPA treatment of cells resulted in partial MAP kinase activation, indicating the presence of PKC-independent pathway. The pathway was inhibited by wortmannin, an inhibitor of PI3-kinase. The results suggest that wortmannin-sensitive molecules such as PI3-kinase, are involved in the V1 receptor-mediated activation of the MAP kinase pathway independent of TPA-sensitive PKC.
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PMID:Wortmannin inhibits the activation of MAP kinase following vasopressin V1 receptor stimulation. 854 62

The testis is a complex organ in which local control is achieved by signalling between its constituent cells. Herein we describe the responses of cultured rat testicular cells and a mouse Sertoli cell-line to stimulation by endothelin and ATP, and elsewhere we have shown that rat peritubular myoid cells possess phosphoinositidase C-coupled V1a-vasopressin receptors identical to those of liver (Howl, J. et al, 1995, Endocrinology 136: 2206-2213). 1. Peritubular myoid cells from pre-pubertal rats responded through ETA receptors with PtdIns(4,5)P2 hydrolysis [EC50 for endothelin-1 (ET-1) approximately 0.4 nM], elevation of intracellular [Ca2+], and tyrosine phosphorylation of a variety of cellular proteins. They also showed enhanced adenylate cyclase activity, with an EC50 for ET-1 of approximately 3 nM, also through ETA receptors. Pharmacological elevation of [cAMP] did not immediately change the ET-1-stimulated formation of inositol phosphates, but attenuated the response after several hours. 2. Pre-pubertal rat Sertoli cells showed no detectable responses to ET-1, but responded to FSH with elevated [cAMP] and to ATP with PtdIns(4,5)P2 hydrolysis. PtdIns(4,5)P2 hydrolysis was equally responsive to ATP and UTP, and so appears to be activated by P2U-purinergic receptors. This response was enhanced by protein kinase C inhibition and attenuated by PKC activation. 3. Despite its lack of effect on rat Sertoli cells in primary culture, ET-1 provoked PtdIns(4,5)P2 hydrolysis in the TM4 murine Sertoli cell line (EC50 approximately 0.6 nM), and this response was negatively regulated by protein kinase C activation. 5. No receptor-stimulated activation of phosphoinositase C was detected in 'germ cell' populations, but the non-specific G protein activator A1F4-provoked inositol phosphate accumulation in these cells, so demonstrating their potential to respond through yet to be identified G protein-coupled receptors with phosphoinositidase C activation. 6. Immunoblotting studies showed the presence in rat testis of phosphoinositidase C-beta 1 and the alpha-subunits(s) of the G-protein(s) Gq and/or G11. These studies show that testicular myoid and Sertoli cells use at least three G protein-coupled receptors (V1a-vasopressins, ETA-endothelin and P2U-purinergic) to signal through phosphoinositidase C activation, that ET-1 can activate multiple signalling pathways in myoid cells, and that the ET-1-stimulated phosphoinositidase C responses of myoid and Sertoli cells have different regulatory characteristics.
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PMID:Inositol lipid-mediated signalling in response to endothelin and ATP in the mammalian testis. 856 25

We previously demonstrated that the antiprogestogen RU 486, when superfused on myometrial strips, induces a rapid decrease in spontaneous uterine contractile frequency, an increase in amplitude and duration of contractions, and a concomitant decrease in 6-keto PGF(1alpha) release. In this study, we present further work on the role of calcium transients and the involvement of the PLC/PKC pathway in mediating RU 486 effects. We found no clear causal relationship between the spontaneous contractility controlled by external Ca++ concentration and 6-keto PGF(1alpha) release depending mostly on intracellular Ca++ mobilization. We show that RU 486 strengthened the inhibitory effect of TMB8, a potent inhibitor of internal calcium, on both spontaneous contractility and 6-keto PGF(1alpha), release and antagonized the stimulatory action of thapsigargin, a toxin blocking the endoplasmic reticulum calcium pump (ER Ca++ ATPase). These data indicate that RU 486 could act as an inhibitor of intracellular Ca++ mobilization. A slight but significant decrease of the prostanoid liberation was observed in the presence of U73122, an inhibitor of PLC, but not in the presence of neomycin, another PLC inhibitory compound. PKC inhibitors, staurosporine and H7 did not significantly affect spontaneous 6-keto PGF1alpha release, showing that PIP2 hydrolysis and PKC pathway were not involved in the basal release of the prostacyclin metabolite. Vasopressin (AVP), an agent known to induce contractility of the non-pregnant human uterus, markedly increased 6-keto PGF(1alpha) release in a dose-dependent manner. Stimulation of GTP-regulated proteins (G proteins) by ALF4 was accompanied by a rise in 6-keto PGF(1alpha) liberation and a high contractile activity. The effects of both vasopressin and ALF4- were not significantly opposed by RU 486, indicating that other sources of Ca++, not controlled by the steroid, were involved in the agonist-stimulated prostanoid release. Studies with structurally related RU 486 analogues showed that the steroid effects were not dependent on their antihormonal activity, but rather on a specific 11beta arylsubstitution and a 17beta-hydroxy-13beta-methyl configuration of the 4,9-estradien-3-one molecule.
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PMID:RU 38486 inhibits intracellular calcium mobilization and PGI2 release from human myometrium: mechanisms of action. 900 39

The role of protein kinase C activation and carboxyl-terminal region in rapid desensitization of the vasopressin V1a receptor was investigated in Xenopus oocytes. Preincubation of the oocytes with vasopressin or with the diacylglycerol analog 1-oleoyl-2-acetyl-sn-glycerol (OAG), or direct injection of active protein kinase C, all blunted the calcium response of the V1a receptor. Truncation of the 51 terminal amino acids (S374STOP) modified neither the intracellular calcium response to vasopressin nor its desensitization by vasopressin or OAG. These data suggest that desensitization of the V1a receptor is mediated by PKC activation and that its carboxyl-terminal domain is not required for signal transduction and rapid desensitization.
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PMID:Role of protein kinase C and carboxyl-terminal region in acute desensitization of vasopressin V1a receptor. 928 Mar 6

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