MULTIPLE PEPTIDE RECEPTORS AND SITES OF ACTION IN THE CANINE SMALL INTESTINE (OPIOIDS, MOTILIN, TACHYKININS, INTESTINAL MOTILITY, SUBSTANCE P).

Abstract

Motility of the small intestine is a result of complex neurochemical and hormonal interactions within the intestine. The net motility (contraction) of the intestine is a balance of the influences from the central nervous system, enteric nervous system and hormonal changes in the body. Recently, the discovery of several peptide neurotransmitters common to the brain and the intestine has stimulated new research into the influence of these novel neurotransmitter candidates on intestinal motility at the level of the enteric (intestinal) nervous system. The present studies examined the contractile actions of three families of peptides, the opioids, tachykinins and motilin. Each of these peptide groups has been localized in the intestine, and suggested to function in the control of intestinal motility. The peptides were administered by intraarterial injection to isolated segments of canine small intestine and the resulting contractile activity measured. The results of these experiments demonstrate that all of these peptides may elicit contractile activity of the intestine in very low doses. These actions were further examined, using pharmacological antagonists, to determine the mechanism of action and the receptor types involved in the contractile actions. The opioid peptide induced responses were found to be mediated by two receptor types, mu and delta, located on the enteric nerve and smooth muscle, respectively. Similarly, the tachykinin induced contractions were also found to be due to actions on two receptor types, SP-P and SP-K, located on the nerve and muscle layers, respectively. These data suggest that the opioids and tachykinins may have multiple functions in the intestine dependent on the site of action and the receptor type involved in the response. Administration of motilin induced long-lasting contractile patterns in the intestine. The results also suggest that the actions of motilin are mediated by intermediate neurons of the enteric plexes which synapse on terminal cholinergic motor neurons.