TGR5的发现2003.pdfVIP

THE JOURNAL OF BIOLOGICAL CHEMISTRY Vol. 278, No. 11, Issue of March 14, pp. 9435–9440, 2003 © 2003 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in U.S.A. A G Protein-coupled Receptor Responsive to Bile Acids* Received for publication, September 21, 2002, and in revised form, December 19, 2002 Published, JBC Papers in Press, January 10, 2003, DOI 10.1074/jbc.M209706200 Yuji Kawamata, Ryo Fujii, Masaki Hosoya, Masataka Harada, Hiromi Yoshida, Masanori Miwa, Shoji Fukusumi, Yugo Habata, Takashi Itoh, Yasushi Shintani, Shuji Hinuma‡, Yukio Fujisawa, and Masahiko Fujino From the Discovery Research Laboratories 1, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., Wadai 10, Tsukuba, Ibaraki 300-4293, Japan So far some nuclear receptors for bile acids have been pressive effects on cell-mediated immunity and macrophage identified. However, no cell surface receptor for bile functions (6–8). The phagocytic capacity of the reticuloendo- acids has yet been reported. We found that a novel G thelial system including Kupffer cells is depressed in cholesta- protein-coupled receptor, TGR5, is responsive to bile sis or obstructive jaundice (8). Cholestatic jaundice frequently acids as a cell-surface receptor. Bile acids specifically causes infectious complications and endotoxemia, which are induced receptor internalization, the activation of ex- closely related to elevated serum bile acid levels (7, 9). Fur