A G Protein-coupled Receptor Responsive to Bile Acids

作者：Yuji Kawamata, Ryo Fujii, Masaki Hosoya, Masataka Harada, Hiromi Yoshida, Masanori Miwa, Shoji Fukusumi, Yugo Habata, Takashi Itoh, Yasushi Shintani, Shuji Hinuma, Yukio Fujisawa, Masahiko Fujino · 发表于：Journal of Biological Chemistry · 年份：2003 · DOI：10.1074/jbc.m209706200 · 被引用次数：1636 · 研究领域：Drug Transport and Resistance Mechanisms、Cholesterol and Lipid Metabolism、RNA Interference and Gene Delivery

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.