Effect of docosahexaenoic acid (DHA) on arachidonic acid metabolism and platelet function.
Studies from our laboratory have suggested a role for ferrous iron in the metabolism of arachidonic acid and demonstrated that inhibitors of prostaglandin synthesis exert their effect by complexing with the heme group of cyclooxygenase. Docosahexaenoic acid (DHA) is a potent competitive inhibitor of arachidonic acid metabolism by sheep vesicular gland prostaglandin synthetase. In this study we have evaluated the effect of exogenously added DHA on platelet function and arachidonic acid metabolism. DHA at 150 microM concentration inhibited aggregation of platelets to 450 microM arachidonic acid. At this concentration DHA also inhibited the second wave of the platelet response to the action of agonists such as epinephrine, adenosine diphosphate and thrombin. Inhibition induced by this fatty acid could be overcome by the agonists at higher concentrations. DHA inhibited the conversion of labeled arachidonic acid to thromboxane by intact, washed platelet suspensions. However, platelets in plasma incubated first with DHA then washed and stirred with labeled arachidonate generated as much thromboxane as control platelets. These results suggest that the polyenoic acids, if released in sufficient quantities in the vicinity of cyclooxygenase, could effectively compete for the heme site and inhibit the conversion of arachidonic acid.
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000328:Adult; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood*; D001665:Binding Sites; D001792:Blood Platelets / Q000187:drug effects*; D004281:Docosahexaenoic Acids; D004837:Epinephrine / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood; D013917:Thrombin / Q000494:pharmacology
D001095:Arachidonic Acids; D005231:Fatty Acids, Unsaturated; D004281:Docosahexaenoic Acids; D016718:Arachidonic Acid; D000244:Adenosine Diphosphate; D011451:Prostaglandin-Endoperoxide Synthases; D013917:Thrombin; D004837:Epinephrine