title: Integrative function of adrenaline receptors for glucagon-like peptide-1 exocytosis in enteroendocrine L cell line GLUTag.
abstract: Adrenaline reacts with three types of adrenergic receptors, α1, α2 and β-adrenergic receptors (ARs), inducing many physiological events including exocytosis. Although adrenaline has been shown to induce glucagon-like peptide-1 (GLP-1) secretion from intestinal L cells, the precise molecular mechanism by which adrenaline regulates GLP-1 secretion remains unknown. Here we show by live cell imaging that all types of adrenergic receptors are stimulated by adrenaline in enteroendocrine L cell line GLUTag cells and are involved in GLP-1 exocytosis. We performed RT-PCR analysis and found that α1B-, α2A-, α2B-, and β1-ARs were expressed in GLUTag cells. Application of adrenaline induced a significant increase of intracellular Ca(2+) and cAMP concentration ([Ca(2+)]i and [cAMP]i, respectively), and GLP-1 exocytosis in GLUTag cells. Blockade of α1-AR inhibited adrenaline-induced [Ca(2+)]i increase and exocytosis but not [cAMP]i increase, while blockade of β1-AR inhibited adrenaline-induced [cAMP]i increase and exocytosis but not [Ca(2+)]i increase. Furthermore, overexpression of α2A-AR suppressed the adrenaline-induced [cAMP]i increase and exocytosis. These results suggest that the fine-turning of GLP-1 secretion from enteroendocrine L cells is established by the balance between α1-, α2-, and β-ARs activation.
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: Kazuki
authors.initials: K
authors.lastname: Harada
authors.affiliation: Cell Signaling Group, Waseda Bioscience Research Institute in Singapore (WABIOS), 11 Biopolis Way #05-02 Helios, Singapore 138667, Singapore; Organization for University Research Initiatives, Waseda University, #304, Block 120-4, 513 Wasedatsurumaki-cho, Shinjuku-ku, Tokyo 162-0041, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kitaguchi
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. Electronic address: takatsuboi@bio.c.u-tokyo.ac.jp.
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuboi
mesh_terms: D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers; D019858:Enteroendocrine Cells / Q000166:cytology / Q000378:metabolism*; D004837:Epinephrine / Q000378:metabolism*; D005089:Exocytosis; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D051379:Mice; D008856:Microscopy, Fluorescence; D016133:Polymerase Chain Reaction; D011941:Receptors, Adrenergic / Q000378:metabolism / Q000502:physiology*
chemical_list: D017931:DNA Primers; D011941:Receptors, Adrenergic; D052216:Glucagon-Like Peptide 1; D000242:Cyclic AMP; D002118:Calcium; D004837:Epinephrine
keywords: Adrenaline; Adrenergic receptors; Enteroendocrine L cell; Exocytosis; Glucagon-like peptide-1