The tyrosine kinase inhibitors, genistein and methyl 2,5-dihydroxycinnamate, inhibit the release of (3H) arachidonate from human platelets stimulated by thrombin or collagen
Hargreaves, P.G.; Licking, E.F.; Sargeant, P.; Sage, S.O.; Barnes, M.J.; Farndale, R.W.
Thrombosis and Haemostasis 72(4): 634-642
1994
ISSN/ISBN: 0340-6245 PMID: 7878644 Document Number: 431297
We have investigated the effects of the tyrosine kinase inhibitors, genistein and methyl 2,5-dihydroxycinnamate, on (3H)arachidonic acid release from human platelets. Both tyrosine kinase inhibitors blocked, in a dose-dependent manner, the release of arachidonic acid stimulated by thrombin or suspensions of collagen fibres. Blockade by the tyrosine kinase inhibitors occurred early in the arachidonate release time course. 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 mobilization of Ca-2+ from internal stores. These findings suggest a role for tyrosine kinase activity in the regulation of phospholipase A-2 in platelets stimulated by the physiological ligands, thrombin and collagen.