title: The G protein-coupled receptor family C group 6 subtype A (GPRC6A) receptor is involved in amino acid-induced glucagon-like peptide-1 secretion from GLUTag cells.
abstract: Although amino acids are dietary nutrients that evoke the secretion of glucagon-like peptide 1 (GLP-1) from intestinal L cells, the precise molecular mechanism(s) by which amino acids regulate GLP-1 secretion from intestinal L cells remains unknown. Here, we show that the G protein-coupled receptor (GPCR), family C group 6 subtype A (GPRC6A), is involved in amino acid-induced GLP-1 secretion from the intestinal L cell line GLUTag. Application of l-ornithine caused an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) in GLUTag cells. Application of a GPRC6A receptor antagonist, a phospholipase C inhibitor, or an IP(3) receptor antagonist significantly suppressed the l-ornithine-induced [Ca(2+)](i) increase. We found that the increase in [Ca(2+)](i) stimulated by l-ornithine correlated with GLP-1 secretion and that l-ornithine stimulation increased exocytosis in a dose-dependent manner. Furthermore, depletion of endogenous GPRC6A by a specific small interfering RNA (siRNA) inhibited the l-ornithine-induced [Ca(2+)](i) increase and GLP-1 secretion. Taken together, these findings suggest that the GPRC6A receptor functions as an amino acid sensor in GLUTag cells that promotes GLP-1 secretion.
authors.affiliation: Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro, Tokyo 153-8902, Japan.
authors.forename: Manami
authors.initials: M
authors.lastname: Oya
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kitaguchi
authors.forename: Ramona
authors.initials: R
authors.lastname: Pais
authors.forename: Frank
authors.initials: F
authors.lastname: Reimann
authors.forename: Fiona
authors.initials: F
authors.lastname: Gribble
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuboi
mesh_terms: D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D019858:Enteroendocrine Cells / Q000378:metabolism*; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005786:Gene Expression Regulation; D005822:Genetic Vectors; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008024:Ligands; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009952:Ornithine / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D017550:Spectroscopy, Fourier Transform Infrared; D013997:Time Factors; D014162:Transfection
chemical_list: D000596:Amino Acids; C488584:GPRC6A protein, human; C515750:GPRC6A protein, mouse; D008024:Ligands; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D049452:Green Fluorescent Proteins; D052216:Glucagon-Like Peptide 1; D009952:Ornithine; D019204:GTP-Binding Proteins; D002118:Calcium