Inhibitory effect of CP-96,345, a non-peptide neurokinin-1-receptor antagonist, on neurogenic responses of guinea-pig isolated airway smooth muscle.

Abstract

The actions of CP-96,345, a non-peptide neurokinin-1 receptor antagonist, on the responses evoked by electrical-field stimulation or by acetylcholine and substance P in guinea-pig tracheal and bronchial muscle strips were examined. Electrical-field stimulation evoked a biphasic response, consisting of a cholinergically-mediated fast contraction followed by non-adrenergically-mediated relaxation in tracheal muscle and by a non-cholinergically-mediated slow contraction in bronchial muscle. CP-96,345 (1-10 microM) caused a concentration-dependent and non-selective inhibition in the amplitude of these neurogenic responses, where non-cholinergic contractions were more profoundly inhibited. Submaximal contractions of tracheal and bronchial muscles evoked by exogenous substance P (0.1-3 microM) were partly inhibited by CP-96,345 (1-10 microM), but acetylcholine-induced contractions were hardly inhibited. The results indicate that in guinea-pig isolated airway smooth muscle CP-96,345 can non-selectively inhibit neurogenic responses probably via neurokinin-1 receptor-dependent and independent mechanisms.