Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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