Identification of membrane-type receptor for bile acids (M-BAR)

被引:836
作者
Maruyama, T [1 ]
Miyamoto, Y [1 ]
Nakamura, T [1 ]
Tamai, Y [1 ]
Okada, H [1 ]
Sugiyama, E [1 ]
Nakamura, T [1 ]
Itadani, H [1 ]
Tanaka, K [1 ]
机构
[1] Banyu Pharmaceut Co Ltd, Tsukuba Res Inst, Tsukuba, Ibaraki 3002611, Japan
关键词
G protein-coupled receptor; M-BAR; bile acid; lithocholic acid; nuclear receptor; FXR; orphan GPCR;
D O I
10.1016/S0006-291X(02)02550-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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. (C) 2002 Elsevier Science (USA). All rights reserved.
引用
收藏
页码:714 / 719
页数:6
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