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.

The Gastrointestinal Circulation: Physiology and Pathophysiology

“…There are, however, significant differences between the gastric and duodenal mucosa that may limit a role for this mechanism in the stomach. Most notably, a role for TRPV1 receptors on gastric mucosal EPANs appears unlikely (486) and the threshold pCO 2 (>100 mmHg) needed to elicit a response (457) appears to exceed the CO 2 levels detected in the gastric lumen (50-70 mmHg) (335,472).…”

“…Acid entering the lumen should interact with HCO 3 − to form CO 2 , achieving pCO 2 levels as high as 400 mmHg (415). Indeed, it has been proposed that acidsensing by the epithelium is accomplished via CO 2 rather than pH per se (457). Moreover, the acid-induced duodenal HCO 3 − secretion appears to be a direct result of CO 2 formation (214).…”

Buffer Therapy for Cancer

“…Despite the low pH of the contents released by the stomach, the epithelial cells of the duodenum are maintained in a virtually neutral pH due to a layer of mucus and the secreted bicarbonate, which plays an important component of a larger system of acid-base balance [40, 41]. Between the proximal and distal sections of the duodenum, a gradient of 2 pH units is established.…”

A matter of taste

“…). Taste perception is integrated with input from other sensory organs in what appears to be a most complex, finely tuned and behaviourally modulated manner (Spector & Travers ), with newly developed imaging techniques allowing us ever more insight (Lecrux & Hamel ).…”

“…Obtaining chemosensory information about nutrients, however, is not limited to taste, but occurs widely in the GI tract (Iwatsuki et al 2012, Akiba & Kaunitz 2011, for example, for acids (Holzer 2011, Sjö blom 2011, Dong et al 2011. Airway bitter receptors trigger defensive reflexes (Kinnamon 2012).…”