Energy dependence of restitution in the gastric mucosa

Rapid epithelial repair (restitution) after injury is required to maintain barrier function of the gastrointestinal mucosa and skin and is thought to be a highly ATP-dependent process that would be inhibited under hypoxic con ditions. However, little is known about the metabolic pathways required for restitution. Thus, this study was undertaken to evaluate, in vitro, the ro le of oxidative respiration and glycolysis in restitution after injury. To this end, restitution of the bullfrog gastric mucosa was evaluated under th e following conditions: 1) blockade of mitochondrial respiration; 2) blocka de of glycolysis; or 3) absence of glucose. The extent of mucosal repair af ter injury was evaluated by electrophysiology and morphology. Cell migratio n, repolarization, and the formation of tight junctions after injury occurr ed during blockade of mitochondrial respiration, whereas the recovery of mu cosal barrier function did not. In contrast, glycolytic inhibition complete ly blocked all aspects of restitution by inhibiting the migration of surfac e epithelial cells. Restitution occurred in tissues incubated with glucose- free solutions, suggesting that cells contain sufficient glucose (glycogen) to drive glycolysis for many hours. Our results demonstrate that the glyco lytic pathway is essential for restitution after injury in the bullfrog gas tric mucosa and that all but complete repair of barrier function occurs in the absence of mitochondrial respiration.