Evidence that the contractile response of the guinea-pig ileum to capsaicin is due to substance P release

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Abstract
Summary The mechanism of action of capsaicin on the guinea-pig isolated ileum was studied. Capsaicin (1.5×10−6mol l−1) produced a large contractile response of the ileum which exhibited marked tachyphylaxis. The response was reduced by treatment of preparations with atropine, 5×10−6mol l−1, and by substance P-autodesensitization, and was abolished by a combination of these treatments. It was concluded that capsaicin released both substance P and acetylcholine from the guinea-pig ileum. Evidence for a cholinergic component in the action of high concentrations of substance P was also obtained and therefore it is proposed that capsaicin releases substance P from neurones in the ileum, and the released substance P in turn stimulates cholinergic neurones to release acetylcholine, as well as producing direct muscle contraction.