diethyl-maleate and Bronchial-Spasm

The Paf-acether (platelet-activating factor) induced bronchospasm (Paf-BCS) was studied in the anesthetized guinea-pig. The SRS antagonist, FPL-55712, as well as inhibitors of both lipoxygenase and cyclooxygenase, phenidone, nordihydroguaiaretic acid (NDGA), and benoxaprofen, caused a dose-related antagonism of Paf-BCS. By contrast, selective inhibitors of cyclooxygenase, indomethacin and aspirin, exerted moderate antagonism at intermediate doses, but had no effect at high doses. Furthermore, diethylmaleate (DEM), which impairs leukotriene synthesis by interfering with glutathione (GSH), suppressed Paf-BCS. Taken together, these results demonstrate that the lipoxygenase pathway plays a major part in the bronchospasmogenic effect of Paf-acether in the guinea-pig.

Topics: Animals; Bronchial Spasm; Catechols; Chromones; Cyclooxygenase Inhibitors; Dose-Response Relationship, Drug; Guinea Pigs; Lipoxygenase Inhibitors; Maleates; Masoprocol; Phenindione; Platelet Activating Factor; Propionates