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

Identification of membrane-type receptor for bile acids (M-BAR)
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DOI:
10.1016/s0006-291x(02)02550-0
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发表时间:
2002-11-15
影响因子:
3.1
通讯作者:
Tanaka, K
Tanaka, K
中科院分区:
生物学4区
文献类型:
--
作者:
Maruyama, T;Miyamoto, Y;Tanaka, K

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胆汁酸在膳食脂肪和脂溶维生素的溶解和吸收中起着至关重要的作用。胆汁酸还通过与核受体结合来调节各种酶和转运蛋白的转录,以实现自身和胆固醇的稳态。在这里,我们报道了一种新的胆汁酸受体,一种膜型G蛋白偶联受体(GPCR),BG37。胆汁酸诱导BG37表达细胞内cAMP水平快速升高,且呈剂量依赖关系,但不依赖于核受体表达。不同胆汁酸对BG37表达细胞的效力顺序与对核受体介导的反应的效力顺序不同。这些观察表明,胆汁酸存在两条独立的信号通路:膜型GPCR用于快速信号转导,核受体用于延迟信号转导。BG37在多种特定组织中均有表达,提示其具有生理功能,但仍有待进一步研究。(C)2002年埃尔塞维尔科学公司(美国)。版权所有。
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.