title: A G protein-coupled receptor responsive to bile acids.
abstract: So far some nuclear receptors for bile acids have been identified. However, no cell surface receptor for bile acids has yet been reported. We found that a novel G protein-coupled receptor, TGR5, is responsive to bile acids as a cell-surface receptor. Bile acids specifically induced receptor internalization, the activation of extracellular signal-regulated kinase mitogen-activated protein kinase, the increase of guanosine 5'-O-3-thio-triphosphate binding in membrane fractions, and intracellular cAMP production in Chinese hamster ovary cells expressing TGR5. Our quantitative analyses for TGR5 mRNA showed that it was abundantly expressed in monocytes/macrophages in human and rabbit. Treatment with bile acids was found to suppress the functions of rabbit alveolar macrophages including phagocytosis and lipopolysaccharide-stimulated cytokine productions. We prepared a monocytic cell line expressing TGR5 by transfecting a TGR5 cDNA into THP-1 cells that did not express TGR5 originally. Treatment with bile acids suppressed the cytokine productions in the THP-1 cells expressing TGR5, whereas it did not influence those in the original THP-1 cells, suggesting that TGR5 is implicated in the suppression of macrophage functions by bile acids.
authors.affiliation: Discovery Research Laboratories 1, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Wadai 10, Tsukuba, Ibaraki 300-4293, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Kawamata
authors.forename: Ryo
authors.initials: R
authors.lastname: Fujii
authors.forename: Masaki
authors.initials: M
authors.lastname: Hosoya
authors.forename: Masataka
authors.initials: M
authors.lastname: Harada
authors.forename: Hiromi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Masanori
authors.initials: M
authors.lastname: Miwa
authors.forename: Shoji
authors.initials: S
authors.lastname: Fukusumi
authors.forename: Yugo
authors.initials: Y
authors.lastname: Habata
authors.forename: Takashi
authors.initials: T
authors.lastname: Itoh
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shintani
authors.forename: Shuji
authors.initials: S
authors.lastname: Hinuma
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujisawa
authors.forename: Masahiko
authors.initials: M
authors.lastname: Fujino
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001647:Bile Acids and Salts / Q000737:chemistry* / Q000378:metabolism; D016466:CHO Cells; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000737:chemistry*; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D008969:Molecular Sequence Data; D010587:Phagocytosis; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000378:metabolism*; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014018:Tissue Distribution; D014162:Transfection
chemical_list: D001647:Bile Acids and Salts; D016207:Cytokines; C473772:GPBAR1 protein, human; C513561:Gpbar1 protein, mouse; D008164:Luminescent Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D000242:Cyclic AMP; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins