Duodenal luminal chemosensing; acid, ATP, and nutrients

Intestinal chemosensing of endogenous and exogenous luminal compounds, including acid, CO2, bile acids and nutrients is an emerging area of gastrointestinal research, since gut hormones, particularly including incretins and glucagon-like peptide-2 (GLP-2) are released in response to luminal nutrients. Identification of luminal chemosensors such as nutrient-ligand G-protein coupled receptors (GPCRs) in enteroendocrine cells has linked luminal compounds to the corresponding gut hormone release. Mucosal chemical sensors are necessary to exert physiological responses such as secretion, digestion, absorption, and motility. We have been studying the mechanisms by which luminal compounds are sensed via mucosal acid sensors and GPCRs, which trigger mucosal defense mechanisms. In addition to luminal acid/CO2 sensing in the duodenum, recent studies also show that compounds present post-prandially such as amino acids, bile acids and fatty acids, enhance duodenal mucosal defenses, with digestion following the initial gastric processing. These studies may form the basis for therapies in which luminal nutrients release gut hormones that affect the mucosal protection, appetite, satiety, and systemic metabolisms.