Importance of an alkaline microenvironment for rapid restitution of the rabbit duodenal mucosa in vitro

Abstract

Rapid epithelial restitution after superficial damage of the gastroduodenal mucosa consists of the migration of remaining intact epithelial cells beneath a necrotic layer of mucus and shed cells. Complete reepithelialization occurs within 60 min (rat stomach) to 7 h (rabbit duodenum) and does not involve cell division. The present study investigated rapid restitution of the acid-damaged rabbit duodenal mucosa in vitro under various conditions. Alkaline flux and transmucosal potential difference were measured simultaneously, and computerized morphometry was performed. Rapid restitution was nearly completed 5 h after damage at neutral luminal pH, but it was retarded when the luminal pH (pHL) was kept at 3. Removal of the necrotic layer did not impair restitution at neutral luminal pH but caused delay at acidic pH (pHL = 3.0). Removal of nutrient bicarbonate slightly delayed restitution at pHL = 7.4 and caused complete inhibition at pHL = 3.0. Alkaline secretion was usually stable but was nearly totally abolished after removal of nutrient bicarbonate. The potential difference decreased after acid damage and showed a tendency to recover in parallel with mucosal restitution. This gradual recovery correlated directly with morphometry. The authors assume that rapid restitution of the duodenal mucosa at an acidic luminal pH depends on the presence of a protective necrotic layer and sufficient alkaline secretion to maintain an optimal environment adjacent to the mucosa. Disturbance of this alkaline microenvironment could be important for the development and healing of duodenal ulcer.