BW755C inhibits the 5-lipoxygenase in E-mast cells without affecting degranulation.
The inhibitory effect of the drug BW755C on the 5-lipoxygenase pathway was analyzed for bone marrow-derived murine mast cells, termed E-mast cells. The drug prevented the formation of 5-HETE from exogenous [14C]arachidonic acid when IgE-sensitized cells were challenged by the antigen. BW755C also prevented formation of leukotriene C4 in a dose-dependent fashion when IgE-sensitized mast cells, preincubated with the drug, were activated with either the specific antigen or the ionophore. Leukotriene C4 inhibition occurred with a minimal drug preincubation period of 1 min before the cells were subjected to antigen-dependent activation. BW755C did not affect the degranulation response of these cells. Thus in an intact cell system BW755C prevents 5-lipoxygenation of arachidonic acid. Furthermore, this study reveals that even with transmembrane activation of E-mast cells through their IgE-Fc receptors, granule secretion is not dependent upon corresponding metabolites from the 5-lipoxygenase pathway.
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D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D000818:Animals; D001854:Bone Marrow Cells; D000001:Calcimycin / Q000494:pharmacology; D003594:Cytoplasmic Granules; D004305:Dose-Response Relationship, Drug; D006596:Hexosaminidases / Q000378:metabolism; D006636:Histamine Release; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D007073:Immunoglobulin E / Q000276:immunology; D016859:Lipoxygenase Inhibitors; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D011720:Pyrazoles / Q000494:pharmacology*; D013189:SRS-A / Q000096:biosynthesis; D001619:beta-N-Acetylhexosaminidases
D006893:Hydroxyeicosatetraenoic Acids; D016859:Lipoxygenase Inhibitors; D011720:Pyrazoles; D013189:SRS-A; D007073:Immunoglobulin E; D000001:Calcimycin; C022022:5-hydroxy-6,8,11,14-eicosatetraenoic acid; D015772:4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyrazol-3-amine; D006596:Hexosaminidases; D001619:beta-N-Acetylhexosaminidases