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The ability of selected lipoxygenase inhibitors (LI) to influence allergic and nonallergic histamine secretion was studied. LI were found to exert concentration-dependent inhibition of allergic histamine release from rat peritoneal mast cells (RPMC) with the following IC50s, microM: nordihydroguaiaretic acid (NDGA) = 3.9; 5, 8, 11, 14-eicosatetraynoic acid (ETYA) = 3.8 and BW 755c = greater than 10. Calcium ionophore A23187 (0.2 microM)-induced histamine release from RPMC was also inhibited by these agents in a concentration-dependent fashion. The IC50s, microM were as follows: NDGA = 1.9; ETYA = 5.9 and BW 755c = greater than 10. Allergic histamine release from rabbit mixed leukocytes was inhibited by these drugs. The IC50s, microM, were as follows: NDGA = 1.4; BW 755c = 1.9 and ETYA = 7.2. These data suggest that the products of 5-lipoxygenase(s), e.g., 5-HPETE, 5-HETE, etc., may modulate (regulate) histamine secretion process(es).
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