title: Sensing of amino acids by the gut-expressed taste receptor T1R1-T1R3 stimulates CCK secretion.
abstract: CCK is secreted by endocrine cells of the proximal intestine in response to dietary components, including amino acids. CCK plays a variety of roles in digestive processes, including inhibition of food intake, consistent with a role in satiety. In the lingual epithelium, the sensing of a broad spectrum of L-amino acids is accomplished by the heteromeric amino acid (umami) taste receptor (T1R1-T1R3). T1R1 and T1R3 subunits are also expressed in the intestine. A defining characteristic of umami sensing by T1R1-T1R3 is its potentiation by IMP or GMP. Furthermore, T1R1-T1R3 is not activated by Trp. We show here that, in response to L-amino acids (Phe, Leu, Glu, and Trp), but not D-amino acids, STC-1 enteroendocrine cells and mouse proximal small intestinal tissue explants secrete CCK and that IMP enhances Phe-, Leu-, and Glu-induced, but not Trp-induced, CCK secretion. Furthermore, small interfering RNA inhibition of T1R1 expression in STC-1 cells results in significant diminution of Phe-, Leu-, and Glu-stimulated, but not Trp-stimulated, CCK release. In STC-1 cells and mouse intestine, gurmarin inhibits Phe-, Leu-, and Glu-induced, but not Trp-stimulated, CCK secretion. In contrast, the Ca(2+)-sensing receptor antagonist NPS2143 inhibits Phe-stimulated CCK release partially and Trp-induced CCK secretion totally in mouse intestine. However, NPS2143 has no effect on Leu- or Glu-induced CCK secretion. Collectively, our data demonstrate that functional characteristics and cellular location of the gut-expressed T1R1-T1R3 support its role as a luminal sensor for Phe-, Leu-, and Glu-induced CCK secretion.
authors.affiliation: Epithelial Function and Development Group, Department of Functional and Comparative Genomics, University of Liverpool, Liverpool, UK.
authors.forename: Kristian
authors.initials: K
authors.lastname: Daly
authors.forename: Miran
authors.initials: M
authors.lastname: Al-Rammahi
authors.forename: Andrew
authors.initials: A
authors.lastname: Moran
authors.forename: Marco
authors.initials: M
authors.lastname: Marcello
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Ninomiya
authors.forename: Soraya P
authors.initials: SP
authors.lastname: Shirazi-Beechey
mesh_terms: D000596:Amino Acids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000378:metabolism*; D005260:Female; D041981:Gastrointestinal Tract / Q000187:drug effects / Q000502:physiology*; D007150:Immunohistochemistry; D007295:Inositol Phosphates / Q000378:metabolism; D007536:Isomerism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D009281:Naphthalenes / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010940:Plant Proteins / Q000494:pharmacology; D011492:Protein Hydrolysates / Q000494:pharmacology; D034622:RNA Interference; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects / Q000502:physiology*; D013268:Stimulation, Chemical
chemical_list: D000596:Amino Acids; D007295:Inositol Phosphates; C436740:N-(2-hydroxy-3-(2-cyano-3-chlorophenoxy)propyl)-1,1-dimethyl-2-(2-nephthyl)ethylamine; D009281:Naphthalenes; D010455:Peptides; D010940:Plant Proteins; D011492:Protein Hydrolysates; D043562:Receptors, G-Protein-Coupled; C431926:taste receptors, type 1; C075206:Gurmarin protein, Gymnema sylvestre; D002766:Cholecystokinin