User:BiophysicsExpert/G protein-coupled bile acid receptor
 | This is the sandbox page where you will draft your initial Wikipedia contribution.
If you're starting a new article, you can develop it here until it's ready to go live. If you're working on improvements to an existing article, copy only one section at a time of the article to this sandbox to work on, and be sure to use an edit summary linking to the article you copied from. Do not copy over the entire article. You can find additional instructions here. Remember to save your work regularly using the "Publish page" button. (It just means 'save'; it will still be in the sandbox.) You can add bold formatting to your additions to differentiate them from existing content. |
Article Draft
[edit]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.
History
TGR5 receptors were first discovered by Takaharu Maruyama in 2002 [1]. It was the first membrane bound G protein coupled receptor that was discovered for faster bile acid signaling [2]. Initially, up until the late 90's, bile acids were known only for its metabolic function of emulsifying fats and keeping cholesterol homeostasis. It wasn't until 1999 when they begun exploring into its role as a hormone and signaling molecule with the discovery of the nuclear bile acid receptors, Farnesoid X Receptors (FXR) [3].
Location
TGR5 receptors are primarily located in gastrointestinal tracts where bile acid functions are most prevalent. They can also be found throughout the body, including the nervous system, immune system, and various muscle groups[4].
Bile Acid Effects on TGR5
Bile acid binds to the TGR5 receptor which increases the secretion of GLP-1. GLP-1 is responsible for increasing insulin secretion in the presence of glucose, increases satiety, and increases pancreatic beta cell production (responsible for insulin secretion). GLP-1 is also used in medications to treat type 2 diabetes [5].
GLP-1 undergoes heightened production through 2 pathways. The first being the activation of Adenylyl cyclase and cAMP which begins a secondary messenger cascade to release GLP-1. The second pathway entails the increase in mitochondrial activity which increases the ATP to ADP ratio. This leads to the inactivation of potassium channels and an increase in calcium channel activity, sending a flood of calcium ions which lead to increased GLP-1 secretion.
Role
The primary function of the TGR5 receptor is for the binding of bile acid to elicit second messenger systems in the metabolic role of bile acids. It is also a receptor for other agonists, including activating various other pathways responsible for responses like inflammation [6].
TGR5 receptors are a member of the G protein-coupled receptor (GPCR) superfamily. As mentioned, 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.
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.
References
[edit]- ^ Maruyama, Takaharu; Miyamoto, Yasuhisa; Nakamura, Takao; Tamai, Yoshitaka; Okada, Hiromasa; Sugiyama, Eiji; Nakamura, Tatsuji; Itadani, Hiraku; Tanaka, Kenichi (2002-11-15). "Identification of membrane-type receptor for bile acids (M-BAR)". Biochemical and Biophysical Research Communications. 298 (5): 714–719. doi:10.1016/S0006-291X(02)02550-0. ISSN 0006-291X.
- ^ Foord, Steven M.; Bonner, Tom I.; Neubig, Richard R.; Rosser, Edward M.; Pin, Jean-Phillipe; Davenport, Anthony P.; Spedding, Michael; Harmar, Anthony J. (2005-06-01). "International Union of Pharmacology. XLVI. G Protein-Coupled Receptor List". Pharmacological Reviews. 57 (2): 279–288. doi:10.1124/pr.57.2.5. ISSN 0031-6997. PMID 15914470.
- ^ Wang, Haibo; Chen, Jasmine; Hollister, Kevin; Sowers, Lawrence C; Forman, Barry M (1999-05). "Endogenous Bile Acids Are Ligands for the Nuclear Receptor FXR/BAR". Molecular Cell. 3 (5): 543–553. doi:10.1016/s1097-2765(00)80348-2. ISSN 1097-2765.
{{cite journal}}: Check date values in:|date=(help) - ^ Duboc, Henri; Taché, Yvette; Hofmann, Alan F. (2014-04). "The bile acid TGR5 membrane receptor: From basic research to clinical application". Digestive and Liver Disease. 46 (4): 302–312. doi:10.1016/j.dld.2013.10.021. ISSN 1590-8658. PMC 5953190. PMID 24411485.
{{cite journal}}: Check date values in:|date=(help)CS1 maint: PMC format (link) - ^ Lun, Weijun; Yan, Qihao; Guo, Xinghua; Zhou, Minchuan; Bai, Yan; He, Jincan; Cao, Hua; Che, Qishi; Guo, Jiao; Su, Zhengquan (2024-02-01). "Mechanism of action of the bile acid receptor TGR5 in obesity". Acta Pharmaceutica Sinica B. 14 (2): 468–491. doi:10.1016/j.apsb.2023.11.011. ISSN 2211-3835. PMC 10840437. PMID 38322325.
{{cite journal}}: CS1 maint: PMC format (link) - ^ Guo, Cong; Chen, Wei-Dong; Wang, Yan-Dong (2016-12-26). "TGR5, Not Only a Metabolic Regulator". Frontiers in Physiology. 7. doi:10.3389/fphys.2016.00646. ISSN 1664-042X. PMC 5183627. PMID 28082913.
{{cite journal}}: CS1 maint: PMC format (link) CS1 maint: unflagged free DOI (link)