SYNERGISTIC INTERACTION OF A CALCIUM IONOPHORE, A23187, AND DOPAMINE IN HUMAN PLATELET-AGGREGATION

This study was undertaken to investigate the mechanism(s) of platelet aggregation induced by the synergistic action of dopamine (DA) and a C a2+-ionophore A23187. DA showed no or little effect on aggregation ove r a wide range of concentrations (up to 500 mu M), but did potentiate the aggregation response of A23187. Aggregation induced by A23187 was inhibited by calcium channel blockers (diltiazem and verapamil), recep tor blockers (chlorpromazine and haloperidol) and cyclo-oxygenase inhi bitor (indomethacin). However, the inhibitory effect of these blockers was more marked (with a selectivity ratio of 1.5-28) in the aggregati on induced by synergistic effect of A23187 and DA. A phosphatidylinosi tol 3-kinase (PI 3-kinase) inhibitor, wortmannin (IC50; 25-30 nM), inh ibited aggregation induced by either A23187 alone or A23187 plus DA. T hese data suggest that A23187 and DA act synergistically and that this synergistic effect on platelet aggregation is mediated through multip le signalling pathways.