Involvement of lipoxygenase pathway in docosapentaenoic acid-induced inhibition of platelet aggregation.
The effects of docosapentaenoic acid (DPA) on platelet aggregation and arachidonic acid metabolism were studied in comparison to those of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Collagen- or arachidonic acid-stimulated platelet aggregation was inhibited dose-dependently by n-3 fatty acids, among which DPA was the most potent inhibitor. These fatty acids inhibited U46619-induced aggregation but to almost the same extent. No effect of the acids on thrombin-induced aggregation was observed. Furthermore, these fatty acids suppressed thromboxane A2 formation by platelets which were exposed to collagen or thrombin, or by platelets to which arachidonic acid was added. In these experiments also, DPA was the most potent inhibitor, whereas DHA was the most effective inhibitor of cyclooxygenase-1 activity. DPA enhanced formation of 12-hydroxyeicosatetraenoic acid in response to collagen or from arachidonic acid by intact platelets, while the other two acids had less of an effect. These results suggest that DPA possesses potent activity for interfering with the cyclooxygenase pathway and accelerating the lipoxygenase pathway, thus inhibiting platelet aggregation most effectively.
Akiba
S
S
Department of Pathological Biochemistry, Kyoto Pharmaceutical University, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
Murata
T
T
Kitatani
K
K
Sato
T
T
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000097:blood; D000818:Animals; D003094:Collagen / Q000494:pharmacology; D051545:Cyclooxygenase 1; D015118:Eicosapentaenoic Acid / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000378:metabolism; D008084:Lipoxygenase / Q000378:metabolism*; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011817:Rabbits; D013929:Thromboxane B2 / Q000097:blood
D005231:Fatty Acids, Unsaturated; D007527:Isoenzymes; D010975:Platelet Aggregation Inhibitors; D013929:Thromboxane B2; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D003094:Collagen; D015118:Eicosapentaenoic Acid; D008084:Lipoxygenase; D051545:Cyclooxygenase 1; D011451:Prostaglandin-Endoperoxide Synthases; C026219:docosapentaenoic acid