Luminal chemosensing in the gastroduodenal mucosa

Abstract

Purpose of review We report recently published knowledge regarding gut chemosensory mechanisms focusing on nutrient-sensing G protein-coupled receptors (GPCRs) expressed on gut enteroendocrine cells (EECs), tuft cells, and in afferent nerves in the gastroduodenal mucosa and submucosa. Recent findings Gene profiling of EECs and tuft cells have revealed expression of a variety of nutrient-sensing GPCRs. The density of EEC and tuft cells is altered by luminal environmental changes that may occur following bypass surgery or in the presence of mucosal inflammation. Some EECs and tuft cells are directly linked to sensory nerves in the subepithelial space. Vagal afferent neurons that innervate the intestinal villi express nutrient receptors, contributing to the regulation of duodenal anion secretion in response to luminal nutrients. Nutrients are also absorbed via specific epithelial transporters. Summary Gastric and duodenal epithelial cells are continually exposed to submolar concentrations of nutrients that activate GPCRs expressed on EECs, tuft cells, and submucosal afferent nerves and are also absorbed through specific transporters, regulating epithelial cell proliferation, gastrointestinal (GI) physiological function, and metabolism. The chemical coding and distribution of EECs and tuft cells are keys to the development of GPCR-targeted therapies.

Expression and function of umami receptors T1R1/T1R3 in gastric smooth muscle

“…Recent studies that showed the presence of plasma membrane receptors for nutrients outside the gustatory system, especially in the gut, suggesting a much more complex role of nutrients in the control of gut function, appetite, and even emotional conditions. [1][2][3][4][5][6][7][8] The majority of the research on the receptors for chemosensation has focused on EECs of gut mucosa. Plasma membrane GPCRs for umami and sweet agonists comprise heterodimers of T1R subtype; T1R1/T1R3 for umami and T1R2/T1R3 for sweet receptors.…”

“…GI motility is controlled by neurohumoral agents released from the autonomic and enteric nervous system, glial cells, and enteroendocrine cells (EEC), which modulate the contractility of SMCs. [3][4][5][6][7][8] These new roles for nutrients and their receptors have made a significant impact in the field of GI motility and secretion. 2 The effects of nutrients have recently been expanded by studies that showed the presence of extra-oral nutrient receptors, especially in the gut, and studies to understand their functional significance.…”

“…2 The effects of nutrients have recently been expanded by studies that showed the presence of extra-oral nutrient receptors, especially in the gut, and studies to understand their functional significance. [3][4][5][6][7][8] These new roles for nutrients and their receptors have made a significant impact in the field of GI motility and secretion.…”

Branched Short-Chain Fatty Acid Isovaleric Acid Causes Colonic Smooth Muscle Relaxation via cAMP/PKA Pathway

“…While little is known of the mechanisms of response to BCFA in the gut, the responses to SCFAs (mainly acetate, propionate, and butyrate) are mediated through the fatty acid receptor 2 (FFA2) and/or 3 (FFA3) formerly known as GPR43 and GPR41, respectively. These receptors are expressed in a variety of cells in the gut including enteroendocrine cells, adipocytes, pancreatic cells, immune cells, and enteric neurons; however, their expression in smooth muscle has not been studied [4,5,[7][8][9][10][30][31][32][33][34][35]. Similarly, their role in mediating the response to BCFA has not been studied in any of these cell types in any detail.…”

“…Recent interest has been directed at these SCFA because of their potential role in gut function, glucose homeostasis, appetite, regulation of metabolism, inflammation and immune competence, as well as tumorigenesis and colon cancers. These have been the topic of many recent reviews [3,5,[7][8][9][10][11][12].…”