Comparative effects of indomethacin, acetylenic acids, 15-HETE, nordihydroguaiaretic acid and BW755C on the metabolism of arachidonic acid in human leukocytes and platelets

Abstract

Human leukocytes and platelets were preincubated with inhibitors of the oxidative metabolism of arachidonic acid, viz, indomethacin, BW755C, 5,8,11,14-eicosatetraynoic acid (ETYA), 5,8,11-eicosatriynoic acid, 15S-hydroxy-5,8,11,13-(Z,Z,Z,E)-eicosatetraenoic acid (15-HETE) and nordihydroguaiaretic acid (NDGA), prior to stimulation with the ionophore A23187 in the presence or absence of exogenous arachidonic acid. Eleven metabolites of arachidonic acid derived from the cyclooxygenase and the 5-,12- and 15-lipoxygenases were measured by reversed-phase high pressure liquid chromatography (RP-HPLC). Indomethacin was the best inhibitor of the platelet cyclooxygenase (ID 50 < 10 −7M) as assessed by measurement of 12-hydroxy-heptadecatrienoic acid (HHT); ETYA was the most potent inhibitor of the 12- and 15-lipoxygenases (ID 50 ≈ 3 × 10 −7M) whereas NDGA was the most potent and selective inhibitor of the 5-lipoxygenase (ID 50 ≈ 3 × 10 −7M).