The antiplatelet activity of PMC, a potent alpha-tocopherol analogue, is mediated through inhibition of cyclo-oxygenase

1 PMC, a potent alpha-tocopherol derivative, dose-dependently (5-25 mu M) i nhibited the ATP-release reaction and platelet aggregation in washed human platelets stimulated by agonists (collagen and ADP). 2 PMC also dose-dependently inhibited the intracellular Ca2+ mobilization, whereas it did not inhibit phosphoinositide breakdown in human platelets st imulated by collagen. 3 PMC (10 and 25 mu M) significantly inhibited collagen-stimulated thrombox ane A(2) (TxA(2)) formation in human platelets. On the other hand, PMC (25 and 100 mu M) did not increase the formation of cyclic AMP or cyclic GMP in platelets. Moreover, PMC (25, 100, and 200 mu M) did not affect the thromb oxane synthetase activity of aspirin-treated platelet microsomes. 4 PMC (10 and 25 mu M) markedly inhibited the exogenous arachidonic acid (1 00 mu M)-induced prostaglandin E-2 (PGE(2)) formation in the presence of im idazole (600 mu M) in washed human platelets, indicating that PMC inhibits cyclo-oxygenase activity. 5 We conclude that PMC may exert its anti-platelet aggregation activity by inhibiting cyclooxygenase activity, which leads to reduced prostaglandin fo rmation; this, in turn, is followed by a reduction of TxA2 formation, and f inally inhibition of [Ca2+](i) mobilization and ATP-release.