Inhibition of rabbit platelet activation by lipoxygenase products of arachidonic and linoleic acid.
The hydroperoxy fatty acids, 15-hydroperoxyeicosatetraenoic acid (15-HPETE), 13-hydroperoxy and 9-hydroperoxyoctadecadienoic acid (13- and 9-HPODE) and the corresponding hydroxy compounds (15-HETE and 13-HODE) were synthesized and purified. Washed rabbit platelets were incubated with these fatty acid derivatives before aggregation was induced. Arachidonic acid-induced aggregation, as well as the secretion of ATP and the formation of thromboxane B2 (TXB2) were dose-dependently inhibited by these compounds. Low thrombin-, collagen- and ADP-induced aggregations were also suppressed by 15-HPETE. Platelet activation induced by the calcium ionophore A23187 and by high thrombin concentrations were not affected by 15-HPETE. In addition, doses of 15-HPETE which were inactive by themselves, potentiated the anti-aggregating activity of prostacyclin (PGI2). It is suggested that the hydroperoxy and hydroxy compounds suppress platelet activation by interference with the rise in cytoplasmic calcium in addition to the inhibition of cyclo-oxygenase.
D000255:Adenosine Triphosphate / Q000097:blood; D001095:Arachidonic Acids / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D019787:Linoleic Acid; D008041:Linoleic Acids / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D008084:Lipoxygenase / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013929:Thromboxane B2 / Q000097:blood
D001095:Arachidonic Acids; D008041:Linoleic Acids; D013929:Thromboxane B2; D000255:Adenosine Triphosphate; D019787:Linoleic Acid; D011464:Epoprostenol; D008084:Lipoxygenase