G protein-coupled bile acid receptor explained

The G protein-coupled bile acid receptor 1 (GPBAR1) also known as G-protein coupled receptor 19 (GPCR19), membrane-type receptor for bile acids (M-BAR) or Takeda G protein-coupled receptor 5 (TGR5) is a protein that in humans is encoded by the GPBAR1 gene.^{[1] [2]}

Function

This gene encodes a member of the G protein-coupled receptor (GPCR) superfamily. This protein functions as a cell surface receptor for bile acids. Treatment of cells expressing this GPCR with bile acids induces the production of intracellular cAMP, activation of a MAP kinase signaling pathway, and internalization of the receptor. The receptor is implicated in the suppression of macrophage functions and regulation of energy homeostasis by bile acids.^[3]

One effect of this receptor is to activate deiodinases which convert the prohormone thyroxine (T₄) to the active hormone triiodothyronine (T₃). T₃ in turn activates the thyroid hormone receptor which increases metabolic rate.^{[4] [5]}

Further reading

• Takeda S, Kadowaki S, Haga T . Identification of G protein-coupled receptor genes from the human genome sequence. . FEBS Lett. . 520 . 1–3 . 97–101 . 2002 . 12044878 . 10.1016/S0014-5793(02)02775-8 . 7116392 . etal. free .
• Maruyama T, Miyamoto Y, Nakamura T . Identification of membrane-type receptor for bile acids (M-BAR). . Biochem. Biophys. Res. Commun. . 298 . 5 . 714–9 . 2003 . 12419312 . 10.1016/S0006-291X(02)02550-0 . etal.
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . etal. free .
• Kawamata Y, Fujii R, Hosoya M . A G protein-coupled receptor responsive to bile acids. . J. Biol. Chem. . 278 . 11 . 9435–40 . 2003 . 12524422 . 10.1074/jbc.M209706200 . etal. free .
• Ota T, Suzuki Y, Nishikawa T . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . etal. free .
• Gerhard DS, Wagner L, Feingold EA . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 . etal.
• Watanabe M, Houten SM, Mataki C . Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation. . Nature . 439 . 7075 . 484–9 . 2006 . 16400329 . 10.1038/nature04330 . 2006Natur.439..484W . 4429032 . etal.
• Thomas SM, Bhola NE, Zhang Q . Cross-talk between G protein-coupled receptor and epidermal growth factor receptor signaling pathways contributes to growth and invasion of head and neck squamous cell carcinoma. . Cancer Res. . 66 . 24 . 11831–9 . 2007 . 17178880 . 10.1158/0008-5472.CAN-06-2876 . etal. free .
• Yasuda H, Hirata S, Inoue K . Involvement of membrane-type bile acid receptor M-BAR/TGR5 in bile acid-induced activation of epidermal growth factor receptor and mitogen-activated protein kinases in gastric carcinoma cells. . Biochem. Biophys. Res. Commun. . 354 . 1 . 154–9 . 2007 . 17214962 . 10.1016/j.bbrc.2006.12.168 . etal.
• Keitel V, Reinehr R, Gatsios P . The G-protein coupled bile salt receptor TGR5 is expressed in liver sinusoidal endothelial cells. . Hepatology . 45 . 3 . 695–704 . 2007 . 17326144 . 10.1002/hep.21458 . 24892239 . etal. free .

External links

• Web site: Bile Acid Receptor . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2007-11-01 . 2016-03-03 . https://web.archive.org/web/20160303212103/http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1332 . dead .

Notes and References

1. Kawamata Y, Fujii R, Hosoya M, Harada M, Yoshida H, Miwa M, Fukusumi S, Habata Y, Itoh T, Shintani Y, Hinuma S, Fujisawa Y, Fujino M . A G protein-coupled receptor responsive to bile acids . J. Biol. Chem. . 278 . 11 . 9435–40 . 2003 . 12524422 . 10.1074/jbc.M209706200 . free .
2. Wang H, Tan YZ, Mu RH, Tang SS, Liu X, Xing SY, Long Y, Yuan DH, Hong H . Takeda G Protein-Coupled Receptor 5 Modulates Depression-like Behaviors via Hippocampal CA3 Pyramidal Neurons Afferent to Dorsolateral Septum . Biological Psychiatry . 89 . 11 . 1084–1095 . June 2021 . 33536132 . 10.1016/j.biopsych.2020.11.018 . 227165118 .
3. Web site: Entrez Gene: GPBAR1 G protein-coupled bile acid receptor 1.
4. Watanabe M, Houten SM, Mataki C, Christoffolete MA, Kim BW, Sato H, Messaddeq N, Harney JW, Ezaki O, Kodama T, Schoonjans K, Bianco AC, Auwerx J . Bile acids induce energy expenditure by promoting intracellular thyroid hormone activation . Nature . 439 . 7075 . 484–9 . 2006 . 16400329 . 10.1038/nature04330 . 2006Natur.439..484W . 4429032 .
5. Baxter JD, Webb P . Metabolism: bile acids heat things up . Nature . 439 . 7075 . 402–3 . 2006 . 16437098 . 10.1038/439402a . 2006Natur.439..402B . 45562883 .