Indirect evidence for the inhibition of enteric substance P neurones by opiate agonists but not by capsaicin.
There is good evidence indicating that hyoscine-resistant contractions of the guinea-pig ileum evoked by stimulation of the intramural nerves are mediated by substance P (SP). In the present experiments, non-cholinergic neurogenic ileum contractions to field stimulation (100 imp., 5-50 Hz) were inhibited by the opiate agonists morphine and [D-Met2,Pro5]enkephalinamide (10(-6) M) in a naloxone-reversible manner. Neither morphine nor naloxone influenced the musculodirect contracting effect of histamine. Capsaicin, a drug that has been shown to deplete SP from primary afferent neurones, exerted no long-lasting effect on non-cholinergic contractions to field stimulation. Repeated administration of long trains of stimuli (900 impulses) resulted in a progressive decrease of the contractions evoked. Addition of naloxone (3 X 10(-7) M) restored the original height of the responses. The above inhibitory action of opiate agonists and of repeated long-train stimulation was 3-6 times greater at 5 Hz than at 50 Hz. It is concluded that opiate agonists inhibit the release of SP from intramural neurones of the guinea-pit ileum. The decrease in responses to repeated long-train stimulations is mediated, at least in part, by the release of endogenous opioid substance(s).
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D004558:Electric Stimulation; D005231:Fatty Acids, Unsaturated / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007422:Intestines / Q000187:drug effects* / Q000294:innervation; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009474:Neurons / Q000378:metabolism*; D013373:Substance P / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects
D005231:Fatty Acids, Unsaturated; D009294:Narcotics; D013373:Substance P; D009270:Naloxone; D009020:Morphine; D002211:Capsaicin