The effect of prednisolone and ketotifen on the antigen‐induced bronchoconstriction and mediator release in rat isolated lungs

Using a new method for inducing IgE‐mediated, systemic anaphylaxis in the rat both prednisolone and ketotifen had been shown previously to be effective in suppressing the bronchial anaphylaxis in vivo. In order to study the mode of action underlying their bronchoprotective effect, both agents were also tested on the antigen‐induced bronchoconstriction in rat isolated lungs in relation to the mediator release in the lung‐effluent. The presence of histamine, 5‐hydroxytryptamine (5‐HT) and SRS‐A could be detected biologically in the lung‐effluent during bronchoconstriction. Histamine and 5‐HT were determined quantitatively by means of h.p.l.c. with fluorimetric detection, whereas SRS‐A was determined using the guinea‐pig ileum in a cascade set‐up. Although both prednisolone and ketotifen inhibited the antigen‐induced bronchoconstriction effectively, it appeared that only prednisolone suppressed the release of histamine, 5‐HT and SRS‐A in the lung‐effluent significantly, whereas ketotifen had no effect. On account of these data it is suggested that the bronchoprotective effect of prednisolone is mainly based on inhibition of the release of the mediators involved, whereas the effect of ketotifen may be based on receptor antagonism. 1985 British Pharmacological Society