6533b7d8fe1ef96bd126ae4e

RESEARCH PRODUCT

Chemosensory signalling pathways involved in sensing of amino acids by the ghrelin cell

Laurien VancleefSandra SteenselsTheo ThijsT. Van Den BroeckJan TackInge DepoortereLoïc Briand

subject

medicine.medical_specialty[ SDV.AEN ] Life Sciences [q-bio]/Food and NutritionEnteroendocrine cellGPRC6ANutrient sensingBiologyArticleReceptors G-Protein-CoupledMice03 medical and health sciences0302 clinical medicineGlucagon-Like Peptide 1Receptor-Interacting Protein Serine-Threonine Kinase 2Taste receptorCell Line TumorInternal medicinemedicineFood and NutritionAnimalsAmino AcidsReceptor030304 developmental biology0303 health sciencesMultidisciplinarydigestive oral and skin physiologyGhrelinEndocrinologySomatostatinReceptor-Interacting Protein Serine-Threonine KinasesAlimentation et NutritionGhrelin[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition030217 neurology & neurosurgeryGhrelin secretionhormones hormone substitutes and hormone antagonistsSignal Transduction

description

AbstractTaste 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.

yearjournalcountryeditionlanguage
2015-10-29Scientific Reports
10.1038/srep15725http://dx.doi.org/10.1038/srep15725