Biology:Beta-3 adrenergic receptor
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Short description: Mammalian protein found in Homo sapiens
 Generic protein structure example |
The beta-3 adrenergic receptor (β3-adrenoceptor), also known as ADRB3, is a beta-adrenergic receptor, and also denotes the human gene encoding it.[1]
Function
Actions of the β3 receptor include
- Enhancement of lipolysis in adipose tissue.[2]
- Thermogenesis in skeletal muscle[3]
It is located mainly in adipose tissue and is involved in the regulation of lipolysis and thermogenesis. Some β3 agonists have demonstrated antistress effects in animal studies, suggesting it also has a role in the central nervous system (CNS). β3 receptors are found in the gallbladder, urinary bladder, and in brown adipose tissue. Their role in gallbladder physiology is unknown, but they are thought to play a role in lipolysis and thermogenesis in brown fat. In the urinary bladder it is thought to cause relaxation of the bladder and prevention of urination.[4]
Mechanism of action
Beta adrenergic receptors are involved in the epinephrine- and norepinephrine-induced activation of adenylate cyclase through the action of the G proteins of the type Gs.[1]
Ligands
Agonists
- Amibegron (SR-58611A)[5][6]
- BRL-37344[7]
- CL-316,243[8]
- L-742,791[9]
- L-796,568[10]
- LY-368,842
- Mirabegron (YM-178),[11] approved for treatment of overactive bladder in Japan, United States, UK, Canada, China and India.
- Nebivolol[12] selective beta(1)-blocker and beta(3)-agonist.
- Ro40-2148
- Solabegron (GW-427,353)[13]
- Vibegron (MK-4618)[14]
Antagonists
- L-748,328[9]
- L-748,337[9]
- SR 59230A was thought to be a selective β3 antagonist[15] but later found to also be an antagonist of the α1 receptor.[16]
Interactions
Beta-3 adrenergic receptor has been shown to interact with Src.[17]
See also
References
- ↑ 1.0 1.1 "Entrez Gene: ADRB3 adrenergic, beta-3-, receptor". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=155.
- ↑ "Combined effects of oleoyl-estrone and a β3-adrenergic agonist (CL316,243) on lipid stores of diet-induced overweight male Wistar rats". Life Sciences 77 (16): 2051–8. September 2005. doi:10.1016/j.lfs.2005.04.008. PMID 15935402. https://zenodo.org/record/889563.
- ↑ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 163
- ↑ "Recent Developments in the Design of Orally Bioavailable β3-Adrenergic Receptor Agonists". Current Medicinal Chemistry 13 (1): 25–37. 2006. doi:10.2174/092986706775198006. PMID 16457637.
- ↑ "Behavioral effects of the β3 adrenoceptor agonist SR58611A: is it the putative prototype of a new class of antidepressant/anxiolytic drugs?". European Journal of Pharmacology 573 (1–3): 139–47. November 2007. doi:10.1016/j.ejphar.2007.06.048. PMID 17669397.
- ↑ "Confirmation of antidepressant potential of the selective β3 adrenoceptor agonist amibegron in an animal model of depression". Pharmacology Biochemistry and Behavior 89 (4): 623–6. June 2008. doi:10.1016/j.pbb.2008.02.020. PMID 18358519.
- ↑ "BRL37344 stimulates GLUT4 translocation and glucose uptake in skeletal muscle via β2-adrenoceptors without causing classical receptor desensitization". American Journal of Physiology. Regulatory, Integrative and Comparative Physiology 316 (5): R666–R677. May 2019. doi:10.1152/ajpregu.00285.2018. PMID 30892909.
- ↑ "The effects of beta(3)-adrenoceptor agonist CL-316,243 on adiponectin, adiponectin receptors and tumor necrosis factor-alpha expressions in adipose tissues of obese diabetic KKAy mice". European Journal of Pharmacology 584 (1): 202–6. 2008. doi:10.1016/j.ejphar.2008.01.028. PMID 18304529.
- ↑ 9.0 9.1 9.2 "Potent and selective human beta(3)-adrenergic receptor antagonists.". The Journal of Pharmacology and Experimental Therapeutics 290 (2): 649–55. Aug 1999. PMID 10411574.
- ↑ "Effect of a 28-d treatment with L-796568, a novel β3-adrenergic receptor agonist, on energy expenditure and body composition in obese men". The American Journal of Clinical Nutrition 76 (4): 780–8. 2002. doi:10.1093/ajcn/76.4.780. PMID 12324291.
- ↑ "Mirabegron for the treatment of overactive bladder". Drugs of Today 48 (1): 25–32. 2012. doi:10.1358/dot.2012.48.1.1738056. PMID 22384458.
- ↑ "Nebivolol, a vasodilating selective beta(1)-blocker, is a beta(3)-adrenoceptor agonist in the nonfailing transplanted human heart". J Am Coll Cardiol 53 (17): 1532–8. 2009. doi:10.1016/j.jacc.2008.11.057. PMID 19389564.
- ↑ "GW427353 (solabegron), a novel, selective beta3-adrenergic receptor agonist, evokes bladder relaxation and increases micturition reflex threshold in the dog". The Journal of Pharmacology and Experimental Therapeutics 323 (1): 202–9. October 2007. doi:10.1124/jpet.107.125757. PMID 17626794.
- ↑ "Discovery of Vibegron: A Potent and Selective β3 Adrenergic Receptor Agonist for the Treatment of Overactive Bladder.". Journal of Medicinal Chemistry 59 (2): 609–23. January 2016. doi:10.1021/acs.jmedchem.5b01372. PMID 26709102.
- ↑ "Functional studies of the first selective β3-adrenergic receptor antagonist SR 59230A in rat brown adipocytes". Mol. Pharmacol. 49 (1): 7–14. 1996. PMID 8569714.
- ↑ "Role of α1- and β3-adrenoceptors in the modulation by SR59230A of the effects of MDMA on body temperature in the mouse". British Journal of Pharmacology 158 (1): 259–66. April 2009. doi:10.1111/j.1476-5381.2009.00186.x. PMID 19422394.
- ↑ "Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activation". J. Biol. Chem. 275 (49): 38131–4. 2000. doi:10.1074/jbc.C000592200. PMID 11013230.
Further reading
- "Rodent and human beta 3-adrenergic receptor genes contain an intron within the protein-coding block". Mol. Pharmacol. 42 (6): 964–70. 1993. PMID 1336117.
- "Molecular characterization of the mouse beta 3-adrenergic receptor: relationship with the atypical receptor of adipocytes". EMBO J. 10 (12): 3721–7. 1991. doi:10.1002/j.1460-2075.1991.tb04940.x. PMID 1718744.
- "Molecular characterization of the human beta 3-adrenergic receptor". Science 245 (4922): 1118–21. 1989. doi:10.1126/science.2570461. PMID 2570461. Bibcode: 1989Sci...245.1118E.
- "Determination of structural domains for G protein coupling and ligand binding in beta 3-adrenergic receptor". Mol. Pharmacol. 48 (3): 492–8. 1995. PMID 7565630.
- "Evidence for the presence of beta 3-adrenergic receptor mRNA in the human brain". Brain Res. Mol. Brain Res. 29 (2): 369–75. 1995. doi:10.1016/0169-328X(94)00274-I. PMID 7609625.
- "Genetic variation in the beta 3-adrenergic receptor and an increased capacity to gain weight in patients with morbid obesity". N. Engl. J. Med. 333 (6): 352–4. 1995. doi:10.1056/NEJM199508103330605. PMID 7609752.
- "Characterization of the region of the short arm of chromosome 8 amplified in breast carcinoma". Oncogene 10 (5): 995–1001. 1995. PMID 7898940.
- "The complex of human Gs protein with the beta 3 adrenergic receptor: a computer-aided molecular modeling study". Journal of Molecular Graphics 12 (1): 22–8, 34. 1994. doi:10.1016/0263-7855(94)80004-9. PMID 8011597.
- "Identification, chromosomal location, and genome organization of mammalian G-protein-coupled receptors". Genomics 18 (2): 175–84. 1994. doi:10.1006/geno.1993.1452. PMID 8288218.
- "Tissue distribution of beta 3-adrenergic receptor mRNA in man". J. Clin. Invest. 91 (1): 344–9. 1993. doi:10.1172/JCI116191. PMID 8380813.
- "The promoter and intron/exon structure of the human and mouse beta 3-adrenergic-receptor genes". Eur. J. Biochem. 213 (3): 1117–24. 1993. doi:10.1111/j.1432-1033.1993.tb17861.x. PMID 8389293.
- "Molecular cloning of a human beta 3-adrenergic receptor cDNA". FEBS Lett. 324 (2): 127–30. 1993. doi:10.1016/0014-5793(93)81377-C. PMID 8389717.
- "Pharmacological characterization of a recently described human beta 3-adrenergic receptor mutant". Endocrinology 137 (6): 2638–41. 1996. doi:10.1210/endo.137.6.8641219. PMID 8641219.
- "Association of Trp64Arg mutation of the beta3-adrenergic-receptor with NIDDM and body weight gain". Diabetologia 39 (3): 349–52. 1996. doi:10.1007/BF00418352. PMID 8721782.
- "Association of a genetic variation in the beta 3-adrenergic receptor gene with coronary heart disease among Japanese". Biochem. Biophys. Res. Commun. 232 (3): 728–30. 1997. doi:10.1006/bbrc.1997.6339. PMID 9126344.
- "Polymorphism of the human beta3-adrenoceptor gene forms a well-conserved haplotype that is associated with moderate obesity and altered receptor function". Diabetes 48 (1): 203–5. 1999. doi:10.2337/diabetes.48.1.203. PMID 9892244.
- "Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis". Nat. Genet. 22 (3): 239–47. 1999. doi:10.1038/10297. PMID 10391210.
- "Mutated human beta3-adrenergic receptor (Trp64Arg) lowers the response to beta3-adrenergic agonists in transfected 3T3-L1 preadipocytes". Horm. Metab. Res. 32 (3): 91–6. 2000. doi:10.1055/s-2007-978597. PMID 10786926.
- "Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activation". J. Biol. Chem. 275 (49): 38131–4. 2001. doi:10.1074/jbc.C000592200. PMID 11013230.
- "Role of β3-adrenergic receptors in the action of a tumour lipid mobilizing factor". Br. J. Cancer 86 (3): 424–8. 2002. doi:10.1038/sj.bjc.6600086. PMID 11875710.
External links
- "β3-adrenoceptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2191.
- Human ADRB3 genome location and ADRB3 gene details page in the UCSC Genome Browser.
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