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 A2. The precise mechanism of arachidonic acid release is unknown. An inhibitor of isolated cytosolic phospholipase A2 (cPLA2), arachidonyl trifluoromethyl ketone (AACOCF3), was used to examine the role that cPLA2 plays in this process. AACOCF3 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 AACOCF3. However, AACOCF3 did not inhibit collagen-induced [14C]arachidonic acid release. These data are consistent with the inhibitory effects of AACOCF3 on collagen-induced aggregation involving an action on the conversion of arachidonic acid to thromboxane.
McNicol
A
A
Department of Oral Biology, University of Manitoba, Winnipeg, Canada.
Nickolaychuk
B R
BR
D016718:Arachidonic Acid / Q000032:analysis; D001095:Arachidonic Acids / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D003094:Collagen / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D010741:Phospholipases A / Q000037:antagonists & inhibitors; D054467:Phospholipases A2; D015539:Platelet Activation / Q000187:drug effects*; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013917:Thrombin / Q000494:pharmacology; D013928:Thromboxane A2 / Q000032:analysis
D001095:Arachidonic Acids; D004791:Enzyme Inhibitors; D010975:Platelet Aggregation Inhibitors; C081565:arachidonyltrifluoromethane; D016718:Arachidonic Acid; D000001:Calcimycin; D013928:Thromboxane A2; D003094:Collagen; D010741:Phospholipases A; D054467:Phospholipases A2; D013917:Thrombin; D013755:Tetradecanoylphorbol Acetate