title: Aspirin enhances the sensitivity of human platelet 12-lipoxygenase to inhibition by 15-HETE, an endogenous regulator.
abstract: Human platelets metabolize arachidonic acid via cyclooxygenase (E.C. 1.14.99.1) to thromboxane A2 and the 12-lipoxygenase to 12-hydroxyeicosatetraenoic acid (12-HETE). Aspirin inhibits cyclooxygenase while the neutrophil product 15-Hydroxyeicosatetraenoic acid (15-HETE) is a selective inhibitor of platelet 12-lipoxygenase. The unexpected observation was made that the platelet 12-lipoxygenase of individuals who had ingested aspirin showed up to a twenty-fold increase in sensitivity to inhibition by 15-HETE. This observation was confirmed in platelets treated with aspirin in vitro. Aspirin pretreatment consistently resulted in a decrease in the I50 for 15-HETE from an average of 21.5 microM to only 5.2 +/- 1.5 microM, indicating a probable interaction between the cyclooxygenase and lipoxygenase pathways.
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D001091:Arachidonate Lipoxygenases; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D004357:Drug Synergism; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis / Q000494:pharmacology*; D016859:Lipoxygenase Inhibitors
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; C025984:15-hydroxy-5,8,11,13-eicosatetraenoic acid; D001091:Arachidonate Lipoxygenases; D001241:Aspirin