Involvement of lipoxygenase pathway in docosapentaenoic acid-induced inhibition of platelet aggregation

The effects of docosapentaenoic acid (DP,I) on platelet aggregation and ara chidonic acid metabolism were studied in comparison to those of eicosapenta enoic acid (EP;I) 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 aci ds inhibited U46619-induced aggregation but to almost the same extent. No e ffect of the acids on thrombin-induced aggregation was observed. Furthermor e, these fatty acids suppressed thromboxane A, 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 inhibi tor, whereas DHA was the most effective inhibitor of cyclooxygenase-1 activ ity: DP;I enhanced formation of 12-hydrosyeicosatetraenoic acid in response to collagen or from arachidonic acid by intact platelets, while the other tno acids had less of an effect. These results suggest that DPA possesses p otent activity for interfering with the cyclooxygenase pathway and accelera ting the lipoxygenase pathway; thus inhibiting platelet aggregation most ef fectively.