Luminal ammonia retards restitution of guinea pig injured gastric mucosa in vitro

The present study was conducted to elucidate the mechanisms by which Helico bacter pylori (HP)-derived ammonia causes gastric mucosal injury. Intact sh eets of guinea pig gastric fundic mucosae were incubated in Ussing chambers . Both the luminal and the serosal pH were kept at 7.4. Transmucosal potent ial difference (PD) and electrical resistance (R) were monitored as indices of mucosal integrity. Restitution was evaluated by recovery of PD, R, and transmucosal [H-3] mannitol flux after Triton X-100-induced mucosal injury. The effects of luminal or serosal NH4Cl on function and morphology of unin jured or injured mucosae were examined. In uninjured mucosae, serosal NH4Cl induced more profound decreases in PD and R and more prominent vacuolation in gastric epithelial cells than did luminal NH4Cl. In contrast, luminal N H4Cl markedly inhibited restitution in injured mucosae and caused an extens ive vacuolation in gastric epithelial cells, as did serosal NH4Cl. Transmuc osal ammonia flux was greater in the injured than in the uninjured mucosae. These results suggest that 1) basolateral membrane of gastric epithelial c ells is more permeable to ammonia than apical membrane and 2) luminal ammon ia, at concentrations detected in HP-infected gastric lumen, retards restit ution in injured mucosae.