Role of Opioid Ligands in the Irritable Bowel Syndrome

Abstract

E Corazziari. Role of opioid ligands in the irritable bowel syndrome. Can J Gastroenterol 1999;13(Suppl A):71A-75A. Endogenous opioid peptides -enkephalins, beta-endorphin and dynorphins -are located in specific sites of the brain, the spinal cord, the autonomic ganglia and the enteric nervous system. Endogenous opioids participate in the regulation of nervous visceral afference and sensitivity as well as of several visceral motor function induced by the central nervous system and through the enteroenteric and the myoenteric reflexes. Their final effect on gut physiology is the net and harmonically balanced result of their binding to mu, delta and kappa opioid receptor subtypes. Exogenous opioid receptor ligands with different affinities for the opioid receptor subtypes have been effectively used to modify and normalize altered gut functions. The mu receptor agonists -morphine and, to a greater extent, the meperidine congeners diphenoxylate and loperamide -have been shown to slow gastrointestinal transit by their effects on the circular and longitudinal muscle of the intestine. Diphenoxylate and, more efficiently, loperamide, for the lack of any effect on the central nervous system, have been usefully employed in the treatment of diarrhea in irritable bowel syndrome (IBS) patients. Unlike the mu receptor agonists morphine and loperamide, which invariably stimulate colonic motility, trimebutine, which has almost equal affinity for mu, delta and kappa receptors, has no effect on normal colonic activity but reduces the abnormal increase in postprandial motor activity in IBS patients and accelerates slow large bowel transit in constipated patients. Opioid ligands can be usefully employed to normalize altered visceral sensitivity in IBS patients. The kappa receptor agonist fedotozine exerts its antinociceptive effect by acting on peripheral nerve endings of sensory vagal and nonvagal afferent pathways. Fedotozine has been shown to increase the threshold of perception to colonic distension in experimental conditions and to affect favourably symptoms of IBS in clinical trials. Le rôle des ligands des récepteurs des opiacés dans le syndrome du côlon irritable RÉSUMÉ : Les peptides opiacés endogènes, les encéphalines, bêta-endorphines et dynorphines, sont localisés en certains points spécifiques du cerveau, de la moelle épinière, des ganglions autonomes et du système nerveux entérique. Les opiacés endogènes participent à la régulation de l'afférence et de la sensibilité viscérale nerveuse, de même qu'à diverses fonctions motrices viscérales induites par le système nerveux central et par les réflexes entéro-entériques et myo-entériques. Leur effet final sur la physiologie intestinale est l'équilibre harmonieux de leurs liaisons aux sous-types de récepteurs des opiacés mu, delta et kappa. Des ligands des récepteurs des opiacés exogènes présentant des affinités diverses à l'endroit des sous-types de récepteurs des opiacés ont été mis à profit utilement pour modifier et normaliser les anomalies de la fonction intestinale. Le...

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