Differential effects of putative inhibitors on cytosolic and membrane associated platelet lipoxygenase.
The effects of Indomethacin, Esculetin, ETYA (4, 7, 10, 13-eicosatetraynoic acid, U53119), 3-amino-1-trifluoromethyl-7-phenyl-pyrazoline (BW 755C), Quercetin, Phenidone, and Nordihydroguaretic acid (NDGA) on the synthesis of 12-L hydroxyeicosatetraenoic acid (12-HETE) by human platelet 12-lipoxygenases were investigated. Except Indomethacin and Esculetin, all other drugs demonstrated significant inhibitory effect on 12-lipoxygenase activity. The rank order of potency for the inhibition of lipoxygenase in intact human platelets was ETYA greater than Quercetin greater than NDGA greater than Esculetin greater than Indomethacin. BW755C and Indomethacin were effective against platelet cyclooxygenase also. ETYA (U53119) was the most potent and selective inhibitor of platelet lipoxygenases. Results of our studies suggest that known lipoxygenase inhibitors display differential effects on platelet cyclooxygenase as well as membrane and cytosol associated lipoxygenases.
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology / Q000031:analogs & derivatives; D000328:Adult; D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors*; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D002462:Cell Membrane / Q000201:enzymology*; D003600:Cytosol / Q000201:enzymology*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol / Q000494:pharmacology; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D011794:Quercetin / Q000494:pharmacology; D013379:Substrate Specificity; D014468:Umbelliferones / Q000494:pharmacology
D016859:Lipoxygenase Inhibitors; D011448:Prostaglandin Antagonists; D011720:Pyrazoles; D014468:Umbelliferones; D015117:5,8,11,14-Eicosatetraynoic Acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; C029510:4,7,10,13-eicosatetraynoic acid; D009637:Masoprocol; D011794:Quercetin; D001091:Arachidonate Lipoxygenases; C015429:phenidone; C007628:esculetin; D007213:Indomethacin