Tumour-promoting phorbol esters inhibit agonist-induced phosphatidate formation and Ca flux in human platelets

Tumour-promoting phorbol esters (phorbol-12-myristate-13-acetate, PMA; phorbol-12,13-dibutyrate, PDBu) but not 4β-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⁺]_j) and on ³²]phosphatidic acid (³²P]PtdOH). PMA and PDBu, but not 4β-phorbol inhibited thrombin-, PAF- and vasopressin-induced elevation of Ca²⁺], and ²⁺P]PtdOH formation. It is suggested that protein kinase C may act to terminate the transduction processes that link receptor occupancy to cellular activation.