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

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.

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.

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).

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.