Luminal chemosensing in the duodenal mucosa

The upper gastrointestinal (GI) mucosa is exposed to endogenous and exogenous chemicals, including gastric acid, CO₂ and nutrients. Mucosal chemical sensors are necessary to exert physiological responses such as secretion, digestion, absorption and motility. We propose the mucosal chemosensing system by which luminal chemicals are sensed to trigger mucosal defence mechanisms via mucosal acid sensors and taste receptors. Luminal acid/CO₂ is sensed via ecto- and cytosolic carbonic anhydrases and ion transporters in the epithelial cells and via acid sensors on the afferent nerves in the duodenum and the oesophagus. Gastric acid sensing is differentially mediated via endocrine cell acid sensors and afferent nerves. Furthermore, a luminal l-glutamate signal is mediated via epithelial l-glutamate receptors, including metabotropic glutamate receptors and taste receptor 1 family heterodimers, with activation of afferent nerves and cyclooxygenase, whereas luminal Ca²(+) is differently sensed via the calcium-sensing receptor in the duodenum. These luminal chemosensors help to activate mucosal defence mechanisms in order to maintain the mucosal integrity and physiological responses of the upper GI tract. Stimulation of luminal chemosensing in the upper GI mucosa may prevent mucosal injury, affect nutrient metabolism and modulate sensory nerve activity.