Differential effects of 15-HPETE on arachidonic acid metabolism in collagen-stimulated human platelets.
The 15-hydroperoxyeicosatetraenoic acid (15-HPETE) has been shown to affect platelet aggregation induced by collagen, arachidonic acid (AA), and PGH2-analogue. Furthermore, it also inhibits the platelet cyclooxygenase and lipoxygenase enzymes, and prostacyclin synthase. The present study was designed to test the effect of 15-HPETE on the mobilization of endogenous AA in collagen-stimulated human platelets. For this purpose, human platelets pretreated with BW755C (a dual inhibitor of cyclooxygenase and lipoxygenase) were stimulated with collagen in the presence of varied concentrations of 15-HPETE. We observed a significant inhibition of oxygenases at all concentrations of 15-HPETE. In contrast, our results indicate that 15-HPETE at lower concentrations (10 microM and 30 microM) significantly stimulated the collagen-induced release of AA from phospholipid sources. Although higher concentrations of 15-HPETE (50 microM and 100 microM) caused some inhibition of AA accumulation in the free fatty acid fraction (25% and 60%), the degree of inhibition was significantly lower than the inhibition observed for the oxygenases (65% and 88% for cyclooxygenase and 77% and 94% for lipoxygenase respectively). These results provide support that hydroperoxides also regulate phospholipases presumably by a different mechanism, which may be important in the detoxification of phospholipid peroxides.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000097:blood* / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D003094:Collagen / Q000494:pharmacology*; D016861:Cyclooxygenase Inhibitors; D006801:Humans; D015289:Leukotrienes; D008054:Lipid Peroxides / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors; D008563:Membrane Lipids / Q000097:blood; D010743:Phospholipids / Q000097:blood
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D015289:Leukotrienes; D008054:Lipid Peroxides; D016859:Lipoxygenase Inhibitors; D008563:Membrane Lipids; D010743:Phospholipids; D016718:Arachidonic Acid; C025086:15-hydroperoxy-5,8,11,13-eicosatetraenoic acid; D003094:Collagen