Identification of membrane-type receptor for bile acids (M-BAR).
Bile acids play an essential role in the solubilization and absorption of dietary fat and lipid-soluble vitamins. Bile acids also modulate the transcription of various genes for enzymes and transport proteins for their own and cholesterol homeostasis through binding to nuclear receptors. Here we report a novel category of bile acid receptor, a membrane-type G protein-coupled receptor (GPCR), BG37. Bile acids induced rapid and dose-dependent elevation of intracellular cAMP levels in BG37-expressing cells, but not in mock-transfected cells, independently of nuclear receptor expression. The rank order of potency of various bile acids for BG37-expressing cells was different from that for the nuclear receptor-mediated response. These observations demonstrate the presence of two independent signaling pathways for bile acids; membrane-type GPCR for rapid signaling and nuclear receptors for delayed signaling. Expression of BG37 was detected in various specific tissues, suggesting its physiological role, although it remains to be further characterized.
Maruyama
Takaharu
T
Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd., Okubo 3, Tsukuba, Ibaraki, Japan.
Miyamoto
Yasuhisa
Y
Nakamura
Takao
T
Tamai
Yoshitaka
Y
Okada
Hiromasa
H
Sugiyama
Eiji
E
Nakamura
Tatsuji
T
Itadani
Hiraku
H
Tanaka
Kenichi
K
D000595:Amino Acid Sequence; D001483:Base Sequence; D001647:Bile Acids and Salts / Q000378:metabolism* / Q000494:pharmacology; D018938:Caco-2 Cells; D002460:Cell Line; D000242:Cyclic AMP / Q000096:biosynthesis; D004247:DNA / Q000235:genetics; D019204:GTP-Binding Proteins / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D001647:Bile Acids and Salts; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018160:Receptors, Cytoplasmic and Nuclear; D004247:DNA; D000242:Cyclic AMP; D019204:GTP-Binding Proteins