Lysophosphatidic acid activates phosphoinositide 3-kinase and phospholipase C in human platelets: inhibitory effects of Wortmannin on phosphoinositide 3-kinase and aggregation.

Lysophosphatidic acid is a biologically active serum phospholipid known to have growth factor-like activities and to cause platelet aggregation. Activated phosphoinositide 3-kinase has been suggested to be involved in cytoskeletal reorganization and mitogenesis. We report that lysophosphatidic acid causes platelet phosphoinositide 3-kinase activation, leading to accumulation of phosphatidylinositol (3, 4, 5) P3 and phosphatidylinositol (3, 4) P2, and stimulates phospholipase C. Worthmannin, a potent inhibitor of phosphoinositide 3-kinase, blocks platelet aggregation induced by lysophosphatidic acid without impairing phospholipase C activation. Eristostatin, an antagonist of fibrinogen binding to platelet integrin, completely blocks platelet aggregation without inhibiting phosphoinositide 3-kinase or phospholipase C. We suggest that lysophosphatidic acid, in activating phosphoinositide 3-kinase, promotes platelet aggregation, but that platelet aggregation in response to lysophosphatidic acid does not significantly enhance phosphoinositide 3-kinase activation.