Neurogenic mechanism of action of motilin in the canine isolated small intestine ex vivo.
The contractile effects of the brain gut peptide motilin were evaluated in isolated, vascularly perfused canine small intestine segments. Motilin (0.04-5.0 micrograms) produced dose-related increases in intraluminal pressure after bolus intraarterial injection. The contractile activity was effectively antagonized by vascular perfusion with either tetrodotoxin (100 ng/ml) or atropine (40 ng/ml), indicating that the primary site of action of motilin was on cholinergic neural elements of the enteric nervous system. Responses to motilin were partially inhibited by hexamethonium perfusion (15 micrograms/ml) suggesting that motilin acts, in part, on preganglionic neural elements proximal to nicotinic cholinergic synapses within the enteric nervous system. No evidence for a direct action of motilin on the smooth muscle of the intestine was observed. Perfusion of the segments with naloxone (up to 3.0 micrograms/ml) did not affect the responses of the bowel to motilin, suggesting that opioid systems are not directly involved in the contractile responses. These data indicate that motilin acts predominantly on cholinergic nerves of the enteric plexes to stimulate contractions of the intestine. In addition, motilin acts, in part, on the preganglionic interneurons of the enteric nervous system and therefore requires intact ganglionic connections. Vascular perfusion with motilin (5-50 ng/ml) also produced dose-related increases in intraluminal pressure suggesting that motilin may act through the circulation in vivo to stimulate intestinal motility. However, these concentrations are significantly greater than those measured during contractile activity in vivo.
D000818:Animals; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004285:Dogs; D066298:In Vitro Techniques; D007421:Intestine, Small / Q000187:drug effects*; D008954:Models, Biological; D009037:Motilin / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D010477:Perfusion; D013779:Tetrodotoxin / Q000494:pharmacology
D009270:Naloxone; D013779:Tetrodotoxin; D009037:Motilin; D004246:Dimethylphenylpiperazinium Iodide