[Effects of tachykinin receptor antagonists on allergic asthma in guinea pigs].

ABSTRACT

In conscious sensitized guinea pigs, CP-96345 (2.06 mumol.kg-1, i.p.), a specific antagonist for tachykinin NK-1 receptors, SR-48968 (1.66 mumol.kg-1, i.p.), an NK-2 receptor antagonist, and the combination of both agents decreased the wheezing percentage and the mortality from anaphylactic shock induced by 0.25% ovalbumin (OA, for 0.5 or 2 min) aerosol inhalation. In the anesthetized guinea pigs, SR-48968 attenuated OA (5 mg.kg-1, i.v.)-induced bronchoconstriction, while CP-96345 inhibited OA-induced Evans blue extravasation in bronchi and intrapulmonary airways. In the isolated tracheal and bronchial smooth muscle preparations of guinea pigs, SR-48968 concentration-dependently inhibited OA (10 micrograms.ml-1)-induced contraction both in trachea and in bronchi, while CP-96345 only attenuated the contraction of bronchi. Pretreatment with capsaicin, a depleting agent of sensory neuropeptides from sensory nerve C-fibers, attenuated the OA-induced contractions both in trachea and in bronchi. The results indicate that (1) tachykinins in the airways are involved in the pathogenesis of allergic asthma; (2) tachykinin receptor antagonists have inhibitory effects on the allergic asthmatic responses, which is at least partly through the inhibition of antigen-induced contraction of airway smooth muscles (NK-2 receptor effect) and airway microvascular leakage (NK-1 receptor effect).