Y. Kamikawa et Y. Shimo, INHIBITORY EFFECT OF CP-96,345, A NONPEPTIDE NEUROKININ-1-RECEPTOR ANTAGONIST, ON NEUROGENIC RESPONSES OF GUINEA-PIG ISOLATED AIRWAY SMOOTH-MUSCLE, Journal of Pharmacy and Pharmacology, 45(10), 1993, pp. 913-916
The actions of CP-96,345. a non-peptide neurokinin-1 receptor antagoni
st, on the responses evoked by electrical-field stimulation or by acet
ylcholine and substance P in guinea-pig tracheal and bronchial muscle
strips were examined. Electrical-field stimulation evoked a biphasic r
esponse, consisting of a cholinergically-mediated fast contraction fol
lowed by non-adrenergically-mediated relaxation in tracheal muscle and
by a non-cholinergically-mediated slow contraction in bronchial muscl
e. CP-96,345(1-10 muM) caused a concentration-dependent and non-select
ive inhibition in the amplitude of these neurogenic responses, where n
on-cholinergic contractions were more profoundly inhibited. Submaximal
contractions of tracheal and bronchial muscles evoked by exogenous su
bstance P (0.13 muM) were partly inhibited by CP-96,345 (1-10 muM), bu
t acetylcholine-induced contractions were hardly inhibited. The result
s indicate that in guinea-pig isolated airway smooth muscle, CP-96,345
can non-selectively inhibit neurogenic responses probably via neuroki
nin-1 receptor-dependent and independent mechanisms.