Sensing of amino acids by the gut-expressed taste receptor T1R1-T1R3 stimulates CCK secretion

  • Kristian Daly
    Epithelial Function and Development Group, Department of Functional and Comparative Genomics, University of Liverpool, Liverpool, United Kingdom;
  • Miran Al-Rammahi
    Epithelial Function and Development Group, Department of Functional and Comparative Genomics, University of Liverpool, Liverpool, United Kingdom;
  • Andrew Moran
    Epithelial Function and Development Group, Department of Functional and Comparative Genomics, University of Liverpool, Liverpool, United Kingdom;
  • Marco Marcello
    Centre for Imaging, Institute of Integrative Biology, University of Liverpool, Liverpool, United Kingdom; and
  • Yuzo Ninomiya
    Section of Oral Neuroscience, Graduate School of Dental Sciences, Kyushu University, Fukuoka, Japan
  • Soraya P. Shirazi-Beechey
    Epithelial Function and Development Group, Department of Functional and Comparative Genomics, University of Liverpool, Liverpool, United Kingdom;

書誌事項

公開日
2013-02-01
資源種別
journal article
DOI
  • 10.1152/ajpgi.00074.2012
公開者
American Physiological Society

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説明

<jats:p>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<jats:sup>2+</jats:sup>-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.</jats:p>

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