Inhibition of collagen-induced platelet activation by arachidonyl trifluoromethyl ketone

Collagen-induced platelet activation is associated with, and markedly potentiated by, the release of arachidonic acid and its subsequent conversion to thromboxane A(2). The precise mechanism of arachidonic acid release is unknown. An inhibitor of isolated cytosolic phospholipase A(2) (cPLA(2)), arachidonyl trifluoromethyl ketone (AACOCF(3)), was used to examine the role that cPLA(2) plays in this process. AACOCF(3) inhibited platelet aggregation in response to collagen and arachidonic acid but not to thrombin, calcium ionophore, phorbol ester, or a thromboxane mimetic. Thromboxane formation stimulated by thrombin or collagen was inhibited by AACOCF(3). However, AACOCF(3) did not inhibit collagen-induced [C-14]arachidonic acid release. These data are consistent with the inhibitory effects of AACOCF(3) on collagen-induced aggregation involving an action on the conversion of arachidonic acid to thromboxane.