Chemosensory signalling pathways involved in sensing of amino acids by the ghrelin cell.
Taste receptors on enteroendocrine cells sense nutrients and transmit signals that control gut hormone release. This study aimed to investigate the amino acid (AA) sensing mechanisms of the ghrelin cell in a gastric ghrelinoma cell line, tissue segments and mice. Peptone and specific classes of amino acids stimulate ghrelin secretion in the ghrelinoma cell line. Sensing of L-Phe occurs via the CaSR, monosodium glutamate via the TAS1R1-TAS1R3 while L-Ala and peptone act via 2 different amino acid taste receptors: CaSR &TAS1R1-TAS1R3 and CaSR &GPRC6A, respectively. The stimulatory effect of peptone on ghrelin release was mimicked ex vivo in gastric but not in jejunal tissue segments, where peptone inhibited ghrelin release. The latter effect could not be blocked by receptor antagonists for CCK, GLP-1 or somatostatin. In vivo, plasma ghrelin levels were reduced both upon intragastric (peptone or L-Phe) or intravenous (L-Phe) administration, indicating that AA- sensing is not polarized and is due to inhibition of ghrelin release from the stomach or duodenum respectively. In conclusion, functional AA taste receptors regulate AA-induced ghrelin release in vitro. The effects differ between stomach and jejunum but these local nutrient sensing mechanisms are overruled in vivo by indirect mechanisms inhibiting ghrelin release.
Gut Peptide Research Lab, Translational Research Center for Gastrointestinal Disorders, Department of Clinical &Experimental Medicine, University of Leuven, Leuven, 3000, Belgium.
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Vancleef
Gut Peptide Research Lab, Translational Research Center for Gastrointestinal Disorders, Department of Clinical &Experimental Medicine, University of Leuven, Leuven, 3000, Belgium.
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Van Den Broeck
Gut Peptide Research Lab, Translational Research Center for Gastrointestinal Disorders, Department of Clinical &Experimental Medicine, University of Leuven, Leuven, 3000, Belgium.
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Thijs
Gut Peptide Research Lab, Translational Research Center for Gastrointestinal Disorders, Department of Clinical &Experimental Medicine, University of Leuven, Leuven, 3000, Belgium.
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Steensels
INRA UMR1324, CNRS UMR6265, Université de Bourgogne, Centre des Sciences du Goût et de l'Alimentation, F-21000, Dijon, France.
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Briand
Gut Peptide Research Lab, Translational Research Center for Gastrointestinal Disorders, Department of Clinical &Experimental Medicine, University of Leuven, Leuven, 3000, Belgium.
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Tack
Gut Peptide Research Lab, Translational Research Center for Gastrointestinal Disorders, Department of Clinical &Experimental Medicine, University of Leuven, Leuven, 3000, Belgium.
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Depoortere
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D045744:Cell Line, Tumor; D054439:Ghrelin / Q000235:genetics / Q000378:metabolism*; D052216:Glucagon-Like Peptide 1 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
D000596:Amino Acids; D054439:Ghrelin; D043562:Receptors, G-Protein-Coupled; D052216:Glucagon-Like Peptide 1; D053475:Receptor-Interacting Protein Serine-Threonine Kinase 2; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C506255:Ripk2 protein, mouse