Dihomogammalinolenic acid, but not eicosapentaenoic acid, activates washed human platelets.
Dihomogammalinolenic acid (2.5-20 microM) added to suspensions of washed human platelets induces platelet shape change and the formation of 1,2-diacylglycerol and phosphatidic acid, indicating the activation of phospholipase C. It also stimulates the phosphorylation of a 40 kDa protein, indicating the activation of protein kinase C. Dihomogammalinolenic acid is converted mainly to 12-hydroxyheptadecadienoic acid and to a smaller extent to prostaglandin E1 and thromboxane B1. Small quantities of the lipoxygenase product 12-hydroxyeicosatrienoic acid are also observed. Indomethacin, by blocking platelet cyclooxygenase, prevents the activation of phospholipase C, protein kinase C, and platelet shape change induced by dihomogammalinolenic acid. Compound UK 38485, a specific thromboxane synthetase inhibitor, does not block platelet activation induced by dihomogammalinolenic acid. The results indicate that endoperoxides derived from dihomogammalinolenic acid, such as prostaglandin G1 or prostaglandin H1, may be responsible for the stimulation of phospholipase C and protein kinase C, and for the induction of platelet shape change. Eicosapentaenoic acid does not activate platelets and is poorly metabolized by platelet cyclooxygenase and lipoxygenase. Eicosapentaenoic acid is a better inhibitor of platelet activation induced by various agonists in washed platelets than dihomogammalinolenic acid. Eicosapentaenoic acid and dihomogammalinolenic acid are, however, equally effective in inhibiting aggregation induced by collagen in platelet-rich plasma. We suggest that eicosapentaenoic acid might be a better antithrombotic agent than dihomogammalinolenic acid.
D015126:8,11,14-Eicosatrienoic Acid / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D015118:Eicosapentaenoic Acid; D004789:Enzyme Activation; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006801:Humans; D008855:Microscopy, Electron, Scanning; D010974:Platelet Aggregation / Q000187:drug effects*; D010738:Type C Phospholipases / Q000097:blood
D005231:Fatty Acids, Unsaturated; D015118:Eicosapentaenoic Acid; D010738:Type C Phospholipases; D015126:8,11,14-Eicosatrienoic Acid