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

The mechanism of action of capsaicin on the guinea-pig isolated ileum was studied. Capsaicin (1.5 x 10(-6) mol 1(-1) produced a large contractile response of the ileum which exhibited marked tachyphylaxis. The response was reduced by treatment of preparations with atropine, 5 x 10(-6) mol 1(-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.