The 5-HT4 receptor agonist mosapride attenuates inflammation of reflux esophagitis.

ABSTRACT

BACKGROUND/AIMS: Chronic inflammatory processes and gastric contents related esophageal mucosal injury are two major characteristics of reflux esophagitis RE). This study was aimed to establish a rat model fitting RE major characteristics and to investigate the effects of mosapride, one of the 5-hydroxy tryptamine (5-HT)4 receptor agonists, on mucosal inflammation in RE. METHODOLOGY: Rat RE model was established by pyloric clip and section ligation-induced chronic acid reflux esophagitis. Animal body weight and survival was monitored. Animals were treated with 0.1 mg/kg/d, 0.5 mg/kg/d, or 2.5 mg/kg/d mosapride by gavage. Gastric emptying was examined. After two weeks, pathological changes of the esophagus were determined and endothelin-1 (ED-1) expression in esophageal tissues was evaluated by immunohistochemistry. RESULTS: No significant differences were observed in the gastric emptying of RE rats after different doses of mosapride treatment (P > 0.05). Gross examination and pathological evaluation revealed that either 0.5 mg/kg/d or 2.5 mg/kg/d mosapride treatment attenuated the mucosal inflammation of RE, but a lower mosapride dose (0.1 mg/kg/d) had limited esophagoprotective effects (P > 0.05). Mosapride treatment greatly decreased the number of ED-1 positive monocytes in the esophagus compared with sham-operated controls (P < 0.05). 5-HT4 receptor and acetylcholine (Ach) receptor antagonists effectively reversed the protective effects of mosapride (P < 0.05). CONCLUSIONS: Our results demonstrated that mosapride attenuated the mucosal inflammation of RE, suggesting that mosapride might provide esophagoprotective effects in addition to its well-known prokinetic actions.