Inhibitory effect of CP-96,345, a non-peptide 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 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.
Kamikawa
Y
Y
Department of Pharmacology, Dokkyo University School of Medicine, Tochigi, Japan.
Shimo
Y
Y
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001980:Bronchi / Q000187:drug effects / Q000294:innervation; D004558:Electric Stimulation; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation* / Q000502:physiology; D064729:Neurokinin-1 Receptor Antagonists; D013373:Substance P / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000294:innervation
D001713:Biphenyl Compounds; D064729:Neurokinin-1 Receptor Antagonists; D013373:Substance P; D000109:Acetylcholine; C066892:CP 96345