Modulation of allergic and nonallergic histamine secretion by lipoxygenase inhibitors.
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).
D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D015117:5,8,11,14-Eicosatetraynoic Acid / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology*; D002396:Catechols / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006636:Histamine Release / Q000187:drug effects*; D006967:Hypersensitivity; D007700:Kinetics; D016859:Lipoxygenase Inhibitors; D009637:Masoprocol / Q000494:pharmacology*; D008407:Mast Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology*; D011720:Pyrazoles / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002396:Catechols; D005231:Fatty Acids, Unsaturated; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D015117:5,8,11,14-Eicosatetraynoic Acid; D000001:Calcimycin; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D009637:Masoprocol