Antagonism of antigen-induced contraction of isolated guinea-pig trachea by 5-lipoxygenase inhibitors.

Tracheal strips were obtained from guinea pigs actively sensitized to chicken ovalbumin (OA). OA-induced contractile responses, obtained by cumulative log addition, were found to be comparable both temporally and in magnitude with responses obtained by single addition of OA. The concentration-response curve obtained by cumulative addition of OA was partially inhibited by pretreatment of tissues with chlorpheniramine. On tracheal spirals treated with chlorpheniramine, indomethacin enhanced OA-induced contractile responses. In the presence of chlorpheniramine and indomethacin, pretreatment with one of the reference 5-lipoxygenase inhibitors (ETYA, NDGA, phenidone or BW-755C) both reduced the maximum contractile response and produced a rightward shift of the OA concentration-response curve. The data suggest that cumulative log addition of OA, on the indomethacin- and chlorpheniramine-treated guinea-pig trachea, is a useful model for evaluating compounds active as either inhibitors of 5-lipoxygenase or antagonists of the products of this pathway.