Cholinergic neurons are involved in the effect of substance P on the circular muscle of the guinea pig small intestine.

The mode of action of the excitatory neuropeptide substance P was studied on the circular muscle of the guinea pig ileum in vitro. Atropine or tetrodotoxin strongly inhibited substance P-induced phasic contractions. The atropine-resistant part of the circular response was blocked by tetrodotoxin. A newly-developed method for quantitative evaluation revealed a rightward displacement of the substance P concentration-response curve, as well as a strong depression of the maximum effect, in the presence of atropine. These results indicate that cholinergic (and probably also non-cholinergic) excitatory neurons mediate phasic contractions due to substance P. The tonic component of the substance P-induced contraction was slightly reduced by atropine.