Inhibition of leukotriene-induced contraction of guinea pig trachea by 5-lipoxygenase inhibitors.

Abstract The effects of the 5-lipoxygenase inhibitors nordihydroguiaretic acid (NDGA), 5,8,11,14-eicosatetraynoic acid (ETYA), 1-phenyl-3-pyrazolidone (phenidone) and BW-755c, on the contractile response to LTC 4 or LTD 4 were examined on the isolated guinea pig trachea. Responses to either LTC 4 or LTD 4 or LTD 4 were obtained on indomethacin treated tissues, in the presence of either L-serine-borate complex or L-cysteine, respectively, to exhibit metabolic conversion of the leukotrienes. NDGA (30 μM) and ETYA (100 μM) produced a selective competitive antagonism of LTD 4 - induced contractions, while phenidone antagonized both LTC 4 - and LTD 4 - induced responses in a non-competitive manner. In contrast, BW-755c (30 μM) did not significantly antagonize LTC 4 or LTD 4 concentration-response curves. The results suggest that leukotriene antagonism may be produced by large concentrations of some 5-lipoxygenase inhibitors.