THE TYROSINE KINASE INHIBITORS, GENISTEIN AND METHYL 2,5-DIHYDROXYCINNAMATE, INHIBIT THE RELEASE OF (H-3)ARACHIDONATE FROM HUMAN PLATELETS STIMULATED BY THROMBIN OR COLLAGEN

We have investigated the effects of the tyrosine kinase inhibitors, ge nistein and methyl 2,5-dihydroxycinnamate, on [H-3]arachidonic acid re lease from human platelets. Both tyrosine kinase inhibitors blocked, i n a dose-dependent manner, the release of arachidonic acid stimulated by thrombin or suspensions of collagen fibres. Blockade by the tyrosin e kinase inhibitors occurred early in the arachidonate release time co urse. Both genistein and methyl 2,5-dihydroxycinnamate also inhibited tyrosine phosphorylation in platelets. The inhibitors were specific in that they did not affect protein kinase C activity, ATP levels or mob ilization of Ca2+ from internal stores. These findings suggest a role for tyrosine kinase activity in the regulation of phospholipase A(2) i n platelets stimulated by the physiological ligands, thrombin and coll agen.