A G protein-coupled receptor responsive to bile acids
A G protein-coupled receptor responsive to bile acids
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DOI：
10.1074/jbc.m209706200
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发表时间：
2003-03-14
影响因子：
4.8
通讯作者：
Fujino, M
中科院分区：
文献类型：
--
作者：
Kawamata, Y;Fujii, R;Fujino, M
迄今为止，一些胆汁酸的核受体已被鉴定。然而，尚未报道胆汁酸的细胞表面受体。我们发现一种新型 G 蛋白偶联受体 TGR5 作为细胞表面受体对胆汁酸有反应。胆汁酸特异性诱导受体内化、细胞外信号调节激酶丝裂原激活蛋白激酶的激活、膜组分中鸟苷 5'-O-3-硫代三磷酸结合的增加以及表达 TGR5 的中国仓鼠卵巢细胞中胞内 cAMP 的产生。我们对 TGR5 mRNA 的定量分析表明，它在人和兔的单核细胞/巨噬细胞中大量表达。研究发现，胆汁酸治疗可抑制兔肺泡巨噬细胞的功能，包括吞噬作用和脂多糖刺激的细胞因子产生。我们通过将TGR5 cDNA转染到最初不表达TGR5的THP-1细胞中来制备表达TGR5的单核细胞系。胆汁酸处理抑制表达 TGR5 的 THP-1 细胞中细胞因子的产生，但不影响原始 THP-1 细胞中的细胞因子产生，表明 TGR5 与胆汁酸抑制巨噬细胞功能有关。
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-thiotriphosphate 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.