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.