Influence of trifluoperazine on platelet aggregation and disaggregation.

Calmodulin has been shown to activate platelet phospholipase A2 and initiate the metabolism of arachidonic acid. Trifluoperazine (stelazine), an agent which selectively binds calmodulin, inhibits phospholipase activity induced by calcium. We have evaluated the effect of this agent on the aggregation, disaggregation and reaggregation of human platelets. Results of our study have shown that stelazine is a selective inhibitor of the second wave response of platelets to the stimulation of agonists. The compound causes dissociation of aggregated platelet clumps and induces a refractory state in dispersed cells. Epinephrine reverses the refractory state and potentiates the response of dissociated cells to the action of thrombin, arachidonate and ionophore A23187. Stelazine elevates cAMP levels to some extent and inhibits release of labeled arachidonic acid from platelet membranes in response to thrombin induced stimulation. Epinephrine may correct stelazine induced inhibition by acting through alpha-adrenergic mechanism, by inducing changes in membrane permeability to calcium, by releasing membrane associated calcium or by directly promoting deacylation of phospholipids.