Evidence that the contractile response of the guinea-pig ileum to capsaicin is due to release of substance P.
1. The possible roles of substance P and opioids in the contractile response of the isolated guinea-pig ileum to the sensory stimulant drug capsaicin were investigated, and the contractions were found to be inhibited by about 60% in preparations desensitized to substance P. 2. Contractions evoked by stimulation of the mesenteric nerves in the presence of the adrenergic blocking drug guanethidine were inhibited by about 75% after the ileum had been rendered insensitive to substance P. 3. Atropine partially inhibited the effect of capsaicin. The atropine-resistant component of the contractile response to capsaicin was inhibited by more than 85% in preparations desensitized to substance P and almost abolished by the substance P antagonist, (D-Pro2,D-Trp7,9)-substance P. 4. The opioid peptide (D-Met2, Pro5)-enkephalinamide inhibited, whereas the opiate antagonist naloxone enhanced the atropine-resistant contractions in response to capsaicin. 5. The results indicate that the contractile response of the guinea-pig ileum to capsaicin and mesenteric nerve stimulation is mediated by release of substance P, presumably from sensory nerve endings in the gut. Substance P appears to act on the smooth muscle both directly and indirectly via cholinergic neurones. It is proposed that opioids modulate the non-cholinergic response to capsaicin by inhibiting the release of substance P.
D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D004723:Endorphins / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D006145:Guanethidine / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000502:physiology; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000502:physiology*; D009270:Naloxone / Q000494:pharmacology; D013373:Substance P / Q000037:antagonists & inhibitors / Q000502:physiology*
D004723:Endorphins; D005231:Fatty Acids, Unsaturated; D013373:Substance P; D009270:Naloxone; D001285:Atropine; D002211:Capsaicin; D006145:Guanethidine