Inability of divalent cation complexes of A23187 to induce platelet secretion

Extracellular calcium produces a dose-dependent inhibition of the early time course of A23187-induced 14C-5HT secretion in human platelets which is independent of the occurrence of aggregation. Pre-incubation of A23187 with calcium to form the A23187-Ca complex results in markedly prolonged lag periods prior to the onset of secretion at Ca concentrations of 0.25 - 1.0 mM and total abolition of the secretion response at 2.0 mM Ca, indicating that these effects of extracellular Ca are due to specific interactions of Ca and A23187. Under conditions which favor dissociation, the complexes of A23187 with Sr, Ca, and Mg, but not Mn, all induce platelet secretion but produce an inhibition of the early secretion response which generally parallels their relative complex stabilities, i.e., Sr less than Ca approximately equal to Mg less than Mn. Under conditions which prevent dissociation, none of these complexes induce secretion. These results indicate that the complexes of A23187 with divalent cations, including Ca, are unable to induce platelet secretion, most likely because of an inability to penetrate the platelet plasma membrane.