Gastrointestinal taste and chemosensory receptors (GI chemoreceptors)

Ectopic taste receptors, primarily the Taste Receptor Type 1 (T1R) and Type 2 (T2R) families, along with related chemosensory receptors like olfactory receptors (ORs), are G protein-coupled receptors (GPCRs) expressed in the enteroendocrine cells (EECs) of the gastrointestinal tract (PubMed: 22414320, PubMed: 28388373). While traditionally associated with oral taste or smell, these receptors function in the gut as luminal sensors that detect sugars, amino acids, and bitter compounds (PubMed: 17724332). Activation of these receptors triggers a signaling cascade involving alpha-gustducin and the TRPM5 ion channel, leading to the secretion of gut hormones such as glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and cholecystokinin (CCK) (PubMed: 24131638). These hormones are essential for regulating glucose homeostasis, gastric emptying, and appetite suppression (PubMed: 30103444). Because of their role in nutrient sensing, these receptors are being explored as therapeutic targets for obesity and type 2 diabetes (PubMed: 26863513). Pharmacological agonists aim to stimulate these pathways to induce satiety and improve insulin sensitivity without caloric intake (PubMed: 25141988). However, the broad expression of some subtypes in other tissues and the potential for inducing nausea remain significant therapeutic challenges (PubMed: 29203873).

Other names

Ectopic taste receptorsExtra-oral taste receptorsGut taste receptorsEnteroendocrine chemosensorsGastrointestinal chemoreceptors

Agonism of T1R or T2R receptors on enteroendocrine cells to stimulate the release of incretins (GLP-1) and satiety peptides (PYY, CCK).