INHIBITORY EFFECT OF CP-96,345, A NONPEPTIDE NEUROKININ-1-RECEPTOR ANTAGONIST, ON NEUROGENIC RESPONSES OF GUINEA-PIG ISOLATED AIRWAY SMOOTH-MUSCLE

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 muM) 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 (0.13 muM) were partly inhibited by CP-96,345 (1-10 muM), 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.