Activation of protein kinase C inhibits hormonal stimulation of the GTPase activity of Gi in human platelets.

The effect of 12-tetradecanoyl phorbol 13-acetate on the GTPase activity of Gi was investigated. Treatment with TPA did not alter basal GTPase activity of membranes or the stimulatory effect of prostaglandin E1 (putatively via Gs). In contrast, the phorbol ester markedly diminished stimulation of GTPase by agents whose receptors are coupled to Gi such as epinephrine (alpha-adrenergic action), platelet activating factor or thrombin. Pertussis toxin catalyzed ADP-ribosylation was also decreased in membranes from TPA-treated platelets as compared to the controls. It is suggested that the alteration in the hormonal activation of the GTPase activity of Gi is secondary to a perturbation in the receptor-Gi interaction.