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

Abstract

1 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. 2 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. 3 Although both prednisolone and ketotifen inhibited the antigen-induced bronchoconstriction effectively, it appeared that only prednisolone suppressed the release ofhistamine, 5-HT and SRS-A in the lung-effluent significantly, whereas ketotifen had no effect. 4 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.

Anti-Allergic Effects of Milrinone and Sulmazole in Isolated Rat Lungs in Comparison with Theophylline

“…We used an isolated lung model which has proven to be useful in the study of anti-allergic drugs [6], All three drugs inhibited anaphylactic bronchoconstriction and vasoconstriction in a similar way with minor differences in potency. The bronchial and vascular smooth-muscle cells were probably the sites of action, since neither of these drugs inhibited anti gen-induced release of preformed mediators by the lungs.…”

“…The animals were sensitized by an intraperitoneal in jection with 2 ml suspension of trinitrophenyl-haptenized ovalbu min (TNP-OVA) together with AIP04 as an adjuvant as described in detail by Ottenhof et al [6]. After 12-21 days the animals were ex amined.…”