BACKGROUND: It has been shown in human and canine studies that motilin, a gastroprokinetic hormone, induces gastric phase III contractions via the enteric nervous; however, the center of motilin action in the stomach has not been clearly revealed. In the present study, we investigated the neural pathway of motilin-induced gastric contraction by using Suncus murinus, a new animal model for motilin study. METHODS: An isolated suncus stomach was used in vitro to determine the mechanism of motilin action through the myenteric plexus. Synthetic suncus motilin (10(-11) -10(-7) molL(-1) ) was added to an organ bath, and the spontaneous contraction response was expressed as a percent of ACh (10(-5) molL(-1) ) responses. Motilin-induced contractions were also studied by a pharmacological method using several receptor antagonists and enzyme inhibitor. KEY RESULTS: Suncus motilin induced a concentration-dependent gastric contraction at concentrations from 10(-9) to 10(-7) molL(-1) . The responses to suncus motilin in the stomach were completely abolished by atropine and tetrodotoxin treatment and significantly suppressed by administration of hexamethonium, verapamil, phentolamine, yohimbine, ondansetron, and naloxone, whereas ritanserin, prazosin, timolol, and FK888 did not affect the action of motilin. Additionally, N-nitro l-arginine methylester slightly potentiated the contractions induced by motilin. CONCLUSIONS & INFERENCES: The results indicate that motilin directly stimulates and modulates suncus gastric contraction through cholinergic, adrenergic, serotonergic, opioidergic, and NO neurons in the myenteric plexus.
BACKGROUND: It has been shown in human and canine studies that motilin, a gastroprokinetic hormone, induces gastric phase III contractions via the enteric nervous; however, the center of motilin action in the stomach has not been clearly revealed. In the present study, we investigated the neural pathway of motilin-induced gastric contraction by using Suncus murinus, a new animal model for motilin study. METHODS: An isolated suncus stomach was used in vitro to determine the mechanism of motilin action through the myenteric plexus. Synthetic suncus motilin (10(-11) -10(-7) molL(-1) ) was added to an organ bath, and the spontaneous contraction response was expressed as a percent of ACh (10(-5) molL(-1) ) responses. Motilin-induced contractions were also studied by a pharmacological method using several receptor antagonists and enzyme inhibitor. KEY RESULTS: Suncus motilin induced a concentration-dependent gastric contraction at concentrations from 10(-9) to 10(-7) molL(-1) . The responses to suncus motilin in the stomach were completely abolished by atropine and tetrodotoxin treatment and significantly suppressed by administration of hexamethonium, verapamil, phentolamine, yohimbine, ondansetron, and naloxone, whereas ritanserin, prazosin, timolol, and FK888 did not affect the action of motilin. Additionally, N-nitro l-arginine methylester slightly potentiated the contractions induced by motilin. CONCLUSIONS & INFERENCES: The results indicate that motilin directly stimulates and modulates suncus gastric contraction through cholinergic, adrenergic, serotonergic, opioidergic, and NO neurons in the myenteric plexus.