Abstract
Human platelet aggregation induced by arachidonic acid (AA, 800μM) and collagen (1μg/ml) was inhibited completely by 400μM of eicosapentaenoic acid (EPA). The acid also inhibited the secondary phase of ADP-induced (3μM) aggregation at the dose, but did not affect the primary phase of that up to 1.6mM. These results consisted with the inhibitory effects of EPA on the biosynthesis of PG endoperoxide by sheep seminal vesicle microsomes and that of thromboxane (TX) A2 by horse platelet microsomes, which both were bioassayed as rabbit aorta contracting activities.
The PGH2-induced (0.8-3.2μM) aggregation and the release reaction, measured as the ATP release, were not inhibited by indomethacin (IND 25μM) and OKY-1581 (10μM). EPA significantly inhibited the PGH2-induced (1.6μM) aggregation at 100μM, but did not abolish it even at 800μM. These results suggest that PGH2 itself can induce the aggregation without conversion to TXA2 and the inhibitory effect of EPA on the PGH2-induced aggregation cannot be explained by the inhibition of TXA2 synthetase. TXA2 induced biphasic aggregation; a primary phase was reversible and not affected by IND, although a secondary phase was irreversible and inhibited by IND. The release reaction was also biphasic. EPA completely inhibited the secondary phase at 100μM, and gradually inhibited the primary phase at higher than 200μM.
These results suggest that EPA not only inhibit the AA metabolism, but also affect the action of the AA metabolites on human platelets.
