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)

Vasopressor hormones alter efflux of glutathione (GSH) and increase permeability of tight junctions in perfused rat liver. Infusions of 10 nM angiotensin II, 10 microM phenylephrine, and 10 nM vasopressin significantly increased efflux of GSH into perfusate by 32-41% and decreased biliary efflux by 31-57%. Direct modulation of protein kinase C (PKC) activity by 600 nM phorbol 12,13-dibutyrate (PDB), 5 microM 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7), 5 microM sphingosine, or 10 nM staurosporine altered the pattern of efflux of GSH but not biliary oxidized glutathione disulfide (GSSG)-GSH ratios. Phorbol dibutyrate mimicked the vasopressor-mediated effects, increasing perfusate efflux by 31% and decreasing biliary efflux by 45%. Inhibitors of PKC caused qualitatively opposite responses, changing perfusate GSH by -37 to 18% and increasing biliary efflux by 22-161%. Whereas vasopressin increased penetration of [14C]sucrose into bile, modulation of PKC activity by PDB and H-7 did not affect the permeability of tight junctions to [14C]sucrose. Although pretreatment with H-7 blocked vasopressin-mediated changes in efflux of GSH, it did not prevent the increase in [14C]sucrose penetrance. We conclude that alterations in sinusoidal and biliary efflux of GSH can occur independent of changes in permeability of hepatocellular tight junctions. These findings suggest a role for protein kinase C in modulating the hepatic efflux of GSH.
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PMID:Effects of vasopressor hormones and modulators of protein kinase C on glutathione efflux from perfused rat liver. 192 46

In primary cultured rat hepatocytes, DNA synthesis was markedly induced 48 h after plating by epidermal growth factor (EGF) and insulin added at 24 h, but not by 12-O-tetradecanoyl-phorbol-13-acetate (TPA). When EGF and insulin were added at 6 h, DNA synthesis at 30 h was 7% of DNA synthesis seen at 48 h, but became 27% by pretreatment with TPA. The similar pretreatment effect was also seen with vasopressin. Such induction at 30 h was inhibited by rat liver plasma membrane added at 2 h even in the presence of TPA or vasopressin, and also by 1-(5-isoquinolinyl-sulfonyl)-2-methylpiperazine more extensively than N-(2-guanidinoethyl)-5-isoquinolinesulfonamide. These results suggest that DNA synthesis induction by EGF and insulin may require a priming period related to protein kinase C activation in primary cultured rat hepatocytes, which is inhibited by plasma membrane.
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PMID:Possible contribution of protein kinase C activation to priming for DNA synthesis induced by epidermal growth factor with insulin and its inhibition by plasma membrane in primary cultured rat hepatocytes. 222 29

Isolated rat neurohypophyses were superfused in vitro and the release of vasopressin and oxytocin into the medium was determined by specific radioimmunoassays. Hormone secretion was increased by electrical stimulation of the pituitary stalk at different frequencies. The effects of several phorbol esters, known to activate phorbol 12,13-dibutyrate, PDB) or not to affect (4 alpha-phorbol 12,13-dideconate and phorbol 12-monoacetate) protein kinase C, and of the direct protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H7) were tested. Electrical stimulation with 450 pulses caused the release of about 45 microU vasopressin and 55 microU oxytocin, when a frequency of 3 Hz was applied, and of about 500 microU vasopressin and oxytocin, when a frequency of 15 Hz was used. PDB (1 mumol/l) increased the release of vasopressin evoked by 15 Hz stimulation maximally by about 40-50% and that evoked by 3 Hz stimulation by about 150%. The release of oxytocin evoked by 15 Hz stimulation was increased by about 150% and that evoked by 3 Hz stimulation by about 400-500% in the presence of PDB. Both inactive phorbol esters had no effects on the evoked release of vasopressin or oxytocin. The effect of PDB on the release of vasopressin and oxytocin was blocked by H7 (10-30 mumol/l). H7 (30 mumol/l) alone reduced the release of vasopressin evoked by stimulation at 15 Hz by 50%. The release of oxytocin was not significantly affected by H7. In the presence of naloxone (1 mumol/l) the release of oxytocin evoked by 3 and 15 Hz stimulation was increased by about 175 and 105%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Frequency-dependent effects of activation and inhibition of protein kinase C on neurohypophysial release of oxytocin and vasopressin. 277 Aug 88

Protein kinase C activity towards exogenous histone was found in a cytosolic fraction of rat renal mesangial cells. The analysis of the 100,000 x g supernatant fraction with DEAE-cellulose ion-exchange chromatography gave a protein kinase C preparation that was dependent on Ca2+ and phosphatidylserine for its activity. The addition of diolein decreased the Ca2+ requirement of the enzyme. 1-(5-Isoquinoline-sulfonyl)-2-methylpiperazine (H-7), sphingosine and cytotoxin I potently inhibited the protein kinase C activity prepared from mesangial cells as well as the 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced prostaglandin synthesis in intact mesangial cells. In the second part of the study, the desensitization of angiotensin II-stimulated phospholipase C activity was investigated. Angiotensin II induced a rapid increase in inositol trisphosphate (IP3) formation. Pretreatment of cells with angiotensin II, followed by removal of the hormone, resulted in a decreased response to a second application of angiotensin II. A similar protocol involving pretreatment with angiotensin II had no effect on subsequent responsiveness to [Arg8]vasopressin. The specific antagonist [Sar1, Ala8]angiotensin II did not stimulate IP3 formation neither did it inhibit the response to a subsequent stimulation with angiotensin II. After angiotensin II pretreatment, a prolonged incubation (120 min) restored responsiveness of the cells to angiotensin II. Pretreatment of mesangial cells with H-7, sphingosine or cytotoxin I almost completely diminished the desensitization of angiotensin II-stimulated IP3 generation. These results indicate that, in rat mesangial cells, angiotensin II induces a homologous desensitization of phospholipase C stimulation. It is proposed that protein kinase C activation plays an important role in the molecular mechanism of desensitization of angiotensin II-stimulated polyphosphoinositide metabolism.
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PMID:Protein kinase C from rat renal mesangial cells: its role in homologous desensitization of angiotensin II-induced polyphosphoinositide hydrolysis. 283 88

Vasopressin and angiotensin II inhibited in a dose-dependent fashion the stimulation of ureagenesis induced by alpha 1-adrenergic activation in hepatocytes incubated in medium without calcium and containing 25 microM EGTA. Vasopressin was more potent than angiotensin II. The effect of different inhibitors of protein kinase C on the alpha 1-adrenergic blockade induced by the vasopressor peptides was tested. It was observed that N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W-7), 4-aminoethyl-1-[2,3-bis(n-decloxyl)-n-propyl]-4-phenylpiperadin e dihydrochloride (CP-46,665-1); 8-(N,N-diethylamino)octyl-3,4, 5-trimethoxybenzoate (TMB-8), polymyxin B and 1-(5-isoquinolynsulfonyl)-2-methylpiperazine (H-7) block this effect of the vasopressor peptides in a dose-dependent fashion. The active phorbol ester, phorbol 12-myristate 13-acetate (PMA), also inhibited the alpha 1-adrenergic stimulation of ureagenesis in these cells. The inhibitors of protein kinase also blocked the effect of phorbol esters but a preincubation with the inhibitors before the addition of PMA was required. alpha 1-Adrenergic activation of phosphatidylinositol labeling was also abolished by PMA; the inhibitors of protein kinase partially blocked this effect of PMA. In summary, our data indicate that inhibitors of protein kinase C can block the alpha 1-adrenergic refractoriness induced by active phorbol esters, vasopressin and angiotensin II. The data are consistent with an important role of protein kinase C in modulating the alpha 1-adrenergic responsiveness of hepatocytes.
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PMID:Inhibitors of protein kinase C block the alpha 1-adrenergic refractoriness induced by phorbol 12-myristate 13-acetate, vasopressin and angiotensin II. 302 3

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

The effects of the protein kinase C inhibitors staurosporine and H-7 [1-(5-isoquinolinylsulfonyl)-2-methylpiperazine] on glucose-induced regulation of glycogen synthase and phosphorylase activities were investigated in the primary culture of hepatocytes. Glycogen synthesis as measured by the incorporation of [14C]glucose into glycogen was enhanced up to 78% (P < .001) by 100 nmol/L staurosporine. In contrast, H-7 inhibited glycogen synthesis in a dose-dependent manner, with an IC50 value of 70 mumol/L. Activation of glycogen synthase by 30 mmol/L glucose was enhanced significantly (P < .02 and less) by staurosporine at 20 nmol/L and higher concentrations whereas the activity of this enzyme was inhibited by H-7 (IC50 = 50 mumol/L). The inactivation of phosphorylase by glucose was significantly greater when staurosporine was included in the medium. However, H-7 increased the phosphorylase activity ratio by 1.5- to 2.5-fold at concentrations of 20 to 100 mumol/L. The time course of synthase activation and phosphorylase inactivation showed that the effect of glucose was enhanced by staurosporine and inhibited by H-7. These novel reciprocal effects of protein kinase C inhibitors were also observed at different concentrations of glucose. The effects of H-8, a compound with structural resemblance to H-7 and an inhibitor of protein kinase A, were similar to those of staurosporine but not to those of H-7. Staurosporine blocked the effects of vasopressin and 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA), whereas H-7 in combination with these protein kinase C activators acted in the same direction. The effects of staurosporine, a relatively more specific inhibitor of protein kinase C, indicated that this enzyme plays a role in the regulation of glycogen metabolism in liver. However, H-7, which is known to have protein kinase C-independent effects in intact cells, seems to alter the activities of glycogen synthase and phosphorylase by a different mechanism.
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PMID:Reciprocal effects of the protein kinase C inhibitors staurosporine and H-7 on the regulation of glycogen synthase and phosphorylase in the primary culture of hepatocytes. 823 44

The present work aimed to determine the role played by protein kinase-C (PKC) in the alpha 1-adrenoceptor-induced activation of hepatic metabolism. The following observations indicate that activation of PKC is a condition necessary for alpha 1-adrenoceptor activation of hepatic functions, but not sufficient to mimic the receptor-mediated effects in the absence of external physiological stimuli. 1) alpha 1-Adrenoceptor activation promoted the translocation of PKC from the cytosol to its active form in the plasma membrane. 2) Activation of PKC by the phorbol ester 12-myristate 13-acetate or exogenous diacylglycerols or by elevation of endogenous levels of diacylglycerols by inhibiting diacylglycerol kinase mimicked the alpha 1-adrenoceptor-mediated actions. However, the time course and magnitude of the nonreceptor responses differ from those mediated by alpha 1-adrenoceptor activation. In addition, nonreceptor-mediated activation of PKC decreased the alpha 1-adrenoceptor responsiveness. 3) Inhibition of PKC by either H-7 [1-(5-isoquinolinilsulfonyl)2-methylpiperazine] or staurosporine inhibited all of the alpha 1-adrenoceptor-induced responses, except gluconeogenesis. The vasopressin effects were not inhibited by H-7, indicating that PKC activation is a distinct feature of the hepatic alpha 1-adrenoceptor activation that is not shared by all the Ca(2+)-mobilizing agonists. The diacylglycerol-PKC branch of the alpha 1-adrenoceptor signaling pathway seems to control the sustained phase of stimulation of hepatic functions. In these studies we have also observed that phorbol 12-myristate 13-acetate produces a concentration-dependent inhibition of hepatic respiration. However, decreased energy availability does not seem to be the cause of its action to decrease alpha 1-adrenoceptor responsiveness.
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PMID:Role of protein kinase-C in the alpha 1-adrenoceptor-mediated responses of perfused rat liver. 840 60