Double action of nicardipine on serotonin release from rat platelets

We studied the effect of nicardipine on the release of preincorporated tritiated serotonin (5-HT) from washed rat platelets and on platelet 5-HT uptake. Nicardipine exerted a complex action. It partially antagonized thrombin-induced 5-HT secretion, but also induced the "selective" release of 5-HT without concomitant ATP release in the absence of platelet activation and inhibited active 5-HT uptake. The two latter effects were observed in the presence of EGTA and therefore could not be related to calcium channel blockade. Verapamil, TMB 8, and the calmodulin antagonists trifluoperazine and R 24571 also possessed this multiplicity of action; however, verapamil and TMB 8 were weaker inducers of selective 5-HT release and uptake inhibition. These results show that, in addition to its inhibitory effect on thrombin-induced platelet activation, nicardipine inhibits platelet 5-HT accumulation. Its administration may therefore result in 5-HT depletion.