Duodenal epithelial sensing of luminal acid: role of carbonic anhydrases

Abstract

Sensing the luminal contents is a prerequisite to activate appropriate gastrointestinal functions. A major task of the duodenal epithelium is to resist the repeated challenges of hydrochloric acid expelled from the stomach. Although extensive research in this field, the complete mechanisms providing this defence remain to be revealed. The duodenal epithelium exports bicarbonate into a submillimetre-thick mucus gel on top of the mucosal surface. Despite the very low pH of the luminal contents, the duodenal mucus-bicarbonate barrier provides a means of maintaining a virtually neutral pH at the epithelial surface. Instead of pH, CO₂ generated by the mixing of acid and bicarbonate at levels not found elsewhere in the body serves as the mediator for sensing the luminal acid. Carbonic anhydrases (CAs) catalyse the reversible hydration of CO₂ and are heavily expressed in the duodenal segment. Accumulating data support the key function of CAs in sensing luminal acid and CO₂. Recent advances demonstrate that the presence of CA II in upper villus plays a crucial role in enterocyte intracellular acidification preceding the secretory increase in response to luminal acid. However, CAs only have a minor role in the bicarbonate supply destined for duodenal bicarbonate secretion into the lumen. The purpose of this review is to summarize the current knowledge of how intraluminal acid is sensed by the duodenal mucosa, with a focus on the role of CAs.