G protein-coupled bile acid receptor 1, member of the class A family of seven-transmembrane G protein-coupled receptors
The G-protein coupled bile acid receptor GPBAR1 is also known as BG37, TGR5 (Takeda G-protein-coupled receptor 5), M-BAR (membrane-type receptor for bile acids), and GPR131. GPBAR1 is highly expressed in the gastrointestinal tract, but also found at many other tissues including liver, colon, heart, skeletal muscle, and brown adipose tissue. GPBAR1 functions as a membrane-bound receptor specific for bile acids, which are the end products of cholesterol metabolism that facilitate digestion and absorption of lipids or fat-soluble vitamins. Bile acids act as liver-specific metabolic signaling molecules and stimulate liver regeneration by activating GPBAR1 and nuclear receptors such as the farnesoid X receptor (FXR). Upon bile acids binding, GPBAR1 activation causes release of the G-alpha(s) subunit and activation of adenylate cyclase. The increase in intracellular cAMP level then stimulates the expression of many genes via the PKA-mediated phosphorylation of cAMP-response element binding protein (CREB). Thus, GPAR1-signalling exerts various biological effects in immune cells, liver, and metabolic tissues. For example, GPBAR1 activation leads to enhanced energy expenditure in brown adipose tissue and skeletal muscle; stimulation of glucagon-like peptide-1 (GLP-1) production in enteroendocrine L-cells; and inhibition of pro-inflammatory cytokine production in macrophages and attenuation of atherosclerosis development. GPBAR1 is a member of the class A rhodopsin-like family of GPCRs, which comprises receptors for hormones, neurotransmitters, sensory stimuli, and a variety of other ligands.
Comment:based on the structures of some class A family members with bound ligands (peptides or chemicals), agonists, or antagonists
Comment:Small-molecule chemical ligands tend to bind deeper within the receptor core, compared to a peptide ligand neurotensin, which binds towards the extracellular surface of its receptor.
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