Tumour-promoting phorbol esters inhibit agonist-induced phosphatidate formation and Ca2+ flux in human platelets.
Tumour-promoting phorbol esters (phorbol-12-myristate-13-acetate, PMA; phorbol-12,13-dibutyrate, PDBu) but not 4 beta-phorbol, activate protein kinase C. Using human platelets pre-labelled with quin2 or 32PO4 we examined the effects of these compounds on human platelet cytosolic free Ca2+ ([Ca2+]i) and on [32P]phosphatidic acid ([32P]PtdOH). PMA and PDBu, but not 4 beta-phorbol inhibited thrombin-, PAF- and vasopressin-induced elevation of [Ca2+]i and [32P]PtdOH formation. It is suggested that protein kinase C may act to terminate the transduction processes that link receptor occupancy to cellular activation.
MacIntyre
D E
DE
McNicol
A
A
Drummond
A H
AH
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000097:blood*; D002273:Carcinogens / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology*; D010704:Phorbols / Q000494:pharmacology*; D010716:Phosphatidylinositols / Q000097:blood*; D010972:Platelet Activating Factor / Q000494:pharmacology; D011493:Protein Kinase C; D011494:Protein Kinases / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D014667:Vasopressins / Q000494:pharmacology
D002273:Carcinogens; D010703:Phorbol Esters; D010704:Phorbols; D010716:Phosphatidylinositols; D010972:Platelet Activating Factor; D014667:Vasopressins; D015240:Phorbol 12,13-Dibutyrate; D011494:Protein Kinases; D011493:Protein Kinase C; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate; D002118:Calcium; C033085:phorbol