Staurosporine and calphostin-C inhibit the phorbol ester-induced decrease of protein kinase C activity in rat hepatocytes.
Two main forms of protein kinase C (PKC 1 and PKC 2) are detected in homogenates of rat hepatocytes using DEAE-cellulose column chromatography. The activity of these forms paradoxically, is rapidly decreased by treatment in vivo with phorbol myristate acetate (PMA). The dose-response curves to PMA for decreasing the activities of PKC 1 and 2 were shifted to the right by the potent and selective PKC inhibitors, staurosporine and calphostin-C. The decreases induced by 100 nM PMA were dose-dependently blocked by these inhibitors. It is concluded that activation of PKC is required and precedes such decreases in activity induced by the active phorbol ester.
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D002848:Chromatography, DEAE-Cellulose; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009281:Naphthalenes; D011083:Polycyclic Compounds / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D019311:Staurosporine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D000470:Alkaloids; D009281:Naphthalenes; D011083:Polycyclic Compounds; D011493:Protein Kinase C; D019311:Staurosporine; C058819:calphostin C; D013755:Tetradecanoylphorbol Acetate