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)

Okadaic acid is a potent and specific inhibitor of protein phosphatases 1 and 2A which seems to be useful for identifying biological processes that are controlled by reversible phosphorylation of proteins. We report here that okadaic acid inhibits in isolated hepatocytes the stimulations of phosphoinositide turnover induced by epinephrine, angiotensin II and vasopressin. Mastoparan, a peptide toxin from wasp venom that mimics receptors by activating G-proteins, also stimulates the accumulation of inositol phosphates in hepatocytes. Interestingly, this action of mastoparan was also inhibited by okadaic acid. Our data indicate that okadaic acid inhibits the phosphoinositide turnover signal transduction system in hepatocytes at a level distal to the receptors.
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PMID:Effect of okadaic acid on hormone- and mastoparan-stimulated phosphoinositide turnover in isolated rat hepatocytes. 165 1

Ca(2+)-dependent and protein kinase C-dependent mechanisms of phospholipase D (PLD) activation were studied in rat hepatocytes by measuring phosphatidylethanol (Peth) formation in the presence of ethanol. Stimulation of Peth formation by 12-O-tetradecanoyl-phorbol 13-acetate (TPA), vasopressin, or A23187 was inhibited by multiple protein kinase C inhibitors or by protein kinase C down-regulation, indicating that this enzyme is involved in the action of all these agents. A controlled elevation of the cytosolic Ca2+ concentration ([Ca2+]cyt) over the range of 0.1-2.0 microM activated Peth formation in the absence of other agonists. Staurosporin potentiated Ca(2+)-induced Peth formation by shifting the [Ca2+]cyt dose-response curve to the left. Other protein kinase C inhibitors (calphostin C, bisindolylmaleimide) inhibited Ca(2+)-mediated Peth formation, but this inhibition was reduced in staurosporin-treated cells. Okadaic acid potentiated PLD activation by TPA, but suppressed PLD activation by elevated [Ca2+]cyt. Desensitization of TPA-induced PLD activity did not affect PLD activation by Ca2+. These data indicate that [Ca2+]cyt and protein kinase C control distinct pathways of PLD activation, but the Ca(2+)-mediated pathway is suppressed by a staurosporin-sensitive protein kinase. Both mechanisms contribute to vasopressin-induced Peth formation in intact hepatocytes. Activation of protein kinase A enhanced vasopressin-induced Peth formation, but not TPA-stimulated or Ca(2+)-stimulated stimulated Peth formation. Protein kinase A acted by enhancing hormonal Ca2+ mobilization, rather than by directly activating PLD, and thereby shifted the balance of Ca(2+)-dependent and protein kinase C-dependent activation mechanisms of PLD in intact cells.
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PMID:The role of cytosolic Ca2+, protein kinase C, and protein kinase A in hormonal stimulation of phospholipase D in rat hepatocytes. 828 38

The effect of the protein phosphatase inhibitor okadaic acid on phospholipase C (PLC)-linked signal transduction processes was investigated in intact hepatocytes. A short (5 min) pretreatment of the hepatocytes with okadaic acid (1 mu M) markedly inhibited a subsequent stimulation of PLC by ethanol as well as by receptor-mediated stimuli (vasopressin and phenylephrine). Okadaic acid inhibited the agonist-induced hydrolysis of polyphosphoinositides, the accumulation of inositol trisphosphate (InsP(3)) and the increase in cytosolic Ca(2+) concentrations. The inhibition could be overcome by high concentrations of vasopressin or ethanol, but only partly so with phenylephrine. A comparison of the sensitivity of different agonists at similar rates of InsP(3) accumulation and Ca(2+) mobilization indicated that ethanol-induced PLC activation was more resistant to the effects of okadaic acid than the hormonal agonists. Moreover, the stimulation of PtdInsP kinase by ethanol, which accompanies PLC activation, was refractory to okadaic acid treatment. These findings suggest that receptor-mediated PLC activation is subject to multiple controls by phosphorylation-dephosphorylation, not all of which affect the actions of ethanol on this signal transduction system.
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PMID:Inhibition of ethanol-induced inositol phosphate formation and Ca(2+) mobilization by okadaic acid in rat hepatocytes: evidence for a role of protein phosphatases in the modulation of phospholipase C by ethanol. 906 20