The role of motilin and cisapride in the enteric nervous system of the lower esophageal sphincter in humans

Abstract

To assess the pharmacophysiological significance of the enteric nervous system and the responses of the human lower esophageal sphincter (LES) to motilin and cisapride, the mechanical responses of esophageal tissues from six patients with esophageal cancer and seven patients with gastric cancer were investigated. Circular muscle reactions were recorded to evaluate the in vitro esophageal responses to electrical field stimulation (EFS), motilin, and cisapride, evoking the adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. The findings of this study revealed that: cholinergic nerves are mainly involved in the regulation of enteric nerves in the steady state, while non-adrenergic non-cholinergic (NANC) inhibitory nerves also exist; motilin may act both via nerves and also directly on the LES smooth muscle; and cisapride releases acetylcholine from the end of the postganglionic fiber of the cholinergic nerve in human LES thereby inducing contraction of the LES. These results suggest that cholinergic and NANC inhibitory nerves play an important role in human LES, and that motilin and cisapride is clinically useful for improving the impaired LES of patients with gastroesophageal reflux.

5‐HT4 receptors on cholinergic nerves involved in contractility of canine and human large intestine longitudinal muscle

“…In the gut, rat oesophagus muscularis mucosae contains smooth muscle 5-HT 4 receptors mediating relaxation (Baxter et al, 1991), an e ect suggested to be absent in the guinea-pig and dog (Cohen et al, 1994). In the human lower oesophageal sphincter, there is evidence for the presence of excitatory 5-HT 4 receptors on the cholinergic nerves (Tomita et al, 1997). In the gastric area, contractile 5-HT 4 receptors have been found on the cholinergic nerves in the guinea-pig (Buchheit & Buhl, 1994), dog (Bingham et al, 1995) and, based on preliminary data, man (Schuurkes et al, 1991).…”

Role of non-adrenergic non-cholinergic inhibitory nerves in the colon of patients with ulcerative colitis

“…3 During the last decade, with the advent of improved techniques in such fields as pharmacology, electrophysiology, and immunohistochemistry, it has been suggested that the NANC nervous system, in addition to the two classical adrenergic and cholonergic components, may play an important role in the regulation of gastrointestinal motility. [4][5][6][7][8] However, the intramural innervation of the colon in patients with UC is not well understood. It seems reasonable to infer, therefore, that investigations of the NANC nervous system in the colon of patients with UC may help to clarify the pathophysiology of impaired colonic motility in this disease.…”

Effect of H. pylori infection on gastrin, ghrelin, motilin, and gastroesophageal reflux

“…Motilin, an endogenous prokinetic hormone, is secreted by gastrointestinal endocrine cells. Besides initiating gastric contraction that distally propagates in the gastrointestinal tract, motilin increases LES pressure acting both via the enteric nervous system and directly on the LES muscle (7). To the best of our knowledge, only a few studies evaluated the effect of H. pylori infection on motilin secretion.…”