Document Detail

Sensing of amino acids by the gut-expressed taste receptor T1R1-T1R3 stimulates CCK secretion.
MedLine Citation:
PMID:  23203156     Owner:  NLM     Status:  MEDLINE    
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.
Kristian Daly; Miran Al-Rammahi; Andrew Moran; Marco Marcello; Yuzo Ninomiya; Soraya P Shirazi-Beechey
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-11-29
Journal Detail:
Title:  American journal of physiology. Gastrointestinal and liver physiology     Volume:  304     ISSN:  1522-1547     ISO Abbreviation:  Am. J. Physiol. Gastrointest. Liver Physiol.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-02-04     Completed Date:  2013-03-19     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  100901227     Medline TA:  Am J Physiol Gastrointest Liver Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  G271-82     Citation Subset:  IM    
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MeSH Terms
Amino Acids / antagonists & inhibitors,  pharmacology*
Blotting, Western
Cell Membrane / metabolism
Cells, Cultured
Cholecystokinin / metabolism*
Gastrointestinal Tract / drug effects,  physiology*
Inositol Phosphates / metabolism
Mice, Inbred C57BL
Microscopy, Confocal
Naphthalenes / pharmacology
Peptides / pharmacology
Plant Proteins / pharmacology
Protein Hydrolysates / pharmacology
RNA Interference
Receptors, G-Protein-Coupled / drug effects,  physiology*
Stimulation, Chemical
Grant Support
//Wellcome Trust
Reg. No./Substance:
0/Amino Acids; 0/Inositol Phosphates; 0/N-(2-hydroxy-3-(2-cyano-3-chlorophenoxy)propyl)-1,1-dimethyl-2-(2-nephthyl)ethylamine; 0/Naphthalenes; 0/Peptides; 0/Plant Proteins; 0/Protein Hydrolysates; 0/Receptors, G-Protein-Coupled; 0/taste receptors, type 1; 138464-10-5/Gurmarin protein, Gymnema sylvestre; 9011-97-6/Cholecystokinin

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