Inhibition of collagen-induced platelet activation by arachidonyl trifluoromethyl ketone |
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| Affiliation: | 1. Division of Neurosurgery, Lebanese American University Medical Center, Beirut, Lebanon;2. Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon;3. Department of Rheumatology, Dubai Hospital, Dubai, United Arab Emirates;4. Division of Rheumatology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut, Lebanon |
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| Abstract: | 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. |
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