Phosphoinositide metabolism in human blood platelets: effects of two types of divalent cation chelators

Phospholipid metabolism was investigated in platelets in relation to secretion of 5-hydroxytryptamine. Both thrombin and the ionophore, A23187, induced secretion of 5-hydroxytryptamine and platelet aggregation accompanied by the specific breakdown of phosphatidyl inositol. The products detected corresponded to phosphatidic acid and a substance which co-chromatographed with polyphosphoinositides and lysophosphatidyl inositol. Thrombin-induced aggregation, secretion and phosphatidyl inositol metabolism were all prevented by EDTA, but only the secretory response was inhibited by the intracellular calcium chelator chlortetracycline (CTC). In contrast, A23187 induced turnover of phosphatidyl inositol in the presence of EDTA even though aggregation and secretion were prevented. All three responses to A23187 were inhibited by chlortetracycline. Thus, platelet aggregation, secretion and phospholipid metabolism can be dissociated by the use of two types of divalent cation chelators: EDTA and CTC. Furthermore, these findings suggest that thrombin and A23187 induce phosphoinositide metabolism by two distinct mechanisms.