Beta-3 adrenergic receptor

The beta-3 adrenergic receptor (β₃-adrenoceptor), also known as ADRB3, is a beta-adrenergic receptor, and also denotes the human gene encoding it.^[5]

ADRB3
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2CDW
Identifiers
Aliases	ADRB3, BETA3AR, adrenoceptor beta 3
External IDs	OMIM: 109691; MGI: 87939; HomoloGene: 37250; GeneCards: ADRB3; OMA:ADRB3 - orthologs
Gene location (Human) Chr. Chromosome 8 (human)[1] Band 8p11.23 Start 37,962,990 bp[1] End 37,966,599 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8 A2|8 15.94 cM Start 27,225,776 bp[2] End 27,250,616 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right ovary left ovary testicle left uterine tube placenta urinary bladder gallbladder gonad muscle layer of sigmoid colon fundus Top expressed in lactiferous gland white adipose tissue brown adipose tissue tunica adventitia of aorta subcutaneous adipose tissue intercostal muscle tunica media of zone of aorta trachea mesenteric lymph nodes embryo More reference expression data BioGPS More reference expression data
Gene ontology Molecular function beta-adrenergic receptor activity G protein-coupled receptor activity epinephrine binding protein homodimerization activity beta3-adrenergic receptor activity norepinephrine binding beta-3 adrenergic receptor binding signal transducer activity adrenergic receptor activity protein binding Cellular component integral component of membrane membrane receptor complex plasma membrane integral component of plasma membrane nucleus Biological process adenylate cyclase-activating G protein-coupled receptor signaling pathway eating behavior adenylate cyclase-modulating G protein-coupled receptor signaling pathway response to antibiotic negative regulation of multicellular organism growth cell-cell signaling G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger human ageing receptor-mediated endocytosis generation of precursor metabolites and energy activation of adenylate cyclase activity diet induced thermogenesis norepinephrine-epinephrine-mediated vasodilation involved in regulation of systemic arterial blood pressure adenylate cyclase-activating adrenergic receptor signaling pathway heat generation brown fat cell differentiation response to cold energy reserve metabolic process temperature homeostasis desensitization of G protein-coupled receptor signaling pathway by arrestin positive regulation of MAPK cascade signal transduction carbohydrate metabolic process G protein-coupled receptor signaling pathway positive regulation of cold-induced thermogenesis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 155 11556 Ensembl ENSG00000188778 ENSMUSG00000031489 UniProt P13945 P25962 RefSeq (mRNA) NM_000025 NM_013462 RefSeq (protein) NP_000016 NP_038490 Location (UCSC) Chr 8: 37.96 – 37.97 Mb Chr 8: 27.23 – 27.25 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Actions of the β₃ receptor include

• Enhancement of lipolysis in adipose tissue.^[6]
• Thermogenesis in skeletal muscle^[7]

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.^[8]

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 G_s.^[5]

Ligands

Agonists

• Amibegron (SR-58611A)^[9][10]
• BRL-37344^[11]
• CL-316,243^[12]
• L-742,791^[13]
• L-796,568^[14]
• LY-368,842
• Mirabegron (YM-178),^[15] approved for treatment of overactive bladder in Japan, United States, UK, Canada, China and India.
• Nebivolol^[16] selective beta(1)-blocker and beta(3)-agonist.
• Ro40-2148
• Solabegron (GW-427,353)^[17]
• Vibegron (MK-4618)^[18]

Antagonists

• L-748,328^[13]
• L-748,337^[13]
• SR 59230A was thought to be a selective β₃ antagonist^[19] but later found to also be an antagonist of the α₁ receptor.^[20]

Interactions

Beta-3 adrenergic receptor has been shown to interact with Src.^[21]

See also

• Other adrenergic receptors
  • Alpha-1 adrenergic receptor
  • Alpha-2 adrenergic receptor
  • Beta-1 adrenergic receptor
  • Beta-2 adrenergic receptor
• Beta blocker

References

1. GRCh38: Ensembl release 89: ENSG00000188778 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000031489 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. "Entrez Gene: ADRB3 adrenergic, beta-3-, receptor".
6. Ferrer-Lorente R, Cabot C, Fernández-López JA, Alemany M (September 2005). "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. doi:10.1016/j.lfs.2005.04.008. PMID 15935402.
7. Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 163
8. Sawa M, Harada H (2006). "Recent Developments in the Design of Orally Bioavailable β3-Adrenergic Receptor Agonists". Current Medicinal Chemistry. 13 (1): 25–37. doi:10.2174/092986706775198006. PMID 16457637.
9. Consoli D, Leggio GM, Mazzola C, Micale V, Drago F (November 2007). "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. doi:10.1016/j.ejphar.2007.06.048. PMID 17669397.
10. Overstreet DH, Stemmelin J, Griebel G (June 2008). "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. doi:10.1016/j.pbb.2008.02.020. PMID 18358519. S2CID 35026036.
11. Mukaida S, Sato M, Öberg AI, Dehvari N, Olsen JM, Kocan M, et al. (May 2019). "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. doi:10.1152/ajpregu.00285.2018. PMID 30892909.
12. Fu L, Isobe K, Zeng Q, Suzukawa K, Takekoshi K, Kawakami Y (2008). "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. doi:10.1016/j.ejphar.2008.01.028. PMID 18304529.
13. Candelore MR, Deng L, Tota L, Guan XM, Amend A, Liu Y, Newbold R, Cascieri MA, Weber AE (August 1999). "Potent and selective human beta(3)-adrenergic receptor antagonists". The Journal of Pharmacology and Experimental Therapeutics. 290 (2): 649–55. PMID 10411574.
14. Larsen TM, Toubro S, van Baak MA, Gottesdiener KM, Larson P, Saris WH, Astrup A (2002). "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. doi:10.1093/ajcn/76.4.780. PMID 12324291.
15. Gras J (2012). "Mirabegron for the treatment of overactive bladder". Drugs of Today. 48 (1): 25–32. doi:10.1358/dot.2012.48.1.1738056. PMID 22384458.
16. Rozec B, Erfanian M, Laurent K, Trochu JN, Gauthier C (2009). "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. doi:10.1016/j.jacc.2008.11.057. PMID 19389564.
17. Hicks A, McCafferty GP, Riedel E, Aiyar N, Pullen M, Evans C, Luce TD, Coatney RW, Rivera GC, Westfall TD, Hieble JP (October 2007). "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. doi:10.1124/jpet.107.125757. PMID 17626794. S2CID 19281697.
18. Edmondson SD, Zhu C, Kar N-F, Di Salvo J, Nagabukuro H, Sacre-Salem B, Dingley, Berger R, Goble SD, Morriello G, Harper B, Moyes CR, Shen D-M, Wang L, Ball R, Fitzmaurice A, Frenkl T, Gichuru LN, Ha S, Hurley AL, Jochnowitz N, Levorse D, Mistry S, Miller RR, Ormes J, Salituro GM, Sanfiz A, Stevenson AS, Villa K, Zamlynny B, Green S, Struthers M, Weber AE (January 2016). "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. doi:10.1021/acs.jmedchem.5b01372. PMID 26709102.
19. Nisoli E, Tonello C, Landi M, Carruba MO (1996). "Functional studies of the first selective β₃-adrenergic receptor antagonist SR 59230A in rat brown adipocytes". Mol. Pharmacol. 49 (1): 7–14. PMID 8569714.
20. Bexis S, Docherty JR (April 2009). "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. doi:10.1111/j.1476-5381.2009.00186.x. PMC 2795232. PMID 19422394.
21. Cao W, Luttrell LM, Medvedev AV, Pierce KL, Daniel KW, Dixon TM, Lefkowitz RJ, Collins S (2000). "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. doi:10.1074/jbc.C000592200. PMID 11013230.

Further reading

• Granneman JG, Lahners KN, Rao DD (1993). "Rodent and human beta 3-adrenergic receptor genes contain an intron within the protein-coding block". Mol. Pharmacol. 42 (6): 964–70. PMID 1336117.
• Nahmias C, Blin N, Elalouf JM, Mattei MG, Strosberg AD, Emorine LJ (1991). "Molecular characterization of the mouse beta 3-adrenergic receptor: relationship with the atypical receptor of adipocytes". EMBO J. 10 (12): 3721–7. doi:10.1002/j.1460-2075.1991.tb04940.x. PMC 453106. PMID 1718744.
• Emorine LJ, Marullo S, Briend-Sutren MM, Patey G, Tate K, Delavier-Klutchko C, Strosberg AD (1989). "Molecular characterization of the human beta 3-adrenergic receptor". Science. 245 (4922): 1118–21. Bibcode:1989Sci...245.1118E. doi:10.1126/science.2570461. PMID 2570461.
• Guan XM, Amend A, Strader CD (1995). "Determination of structural domains for G protein coupling and ligand binding in beta 3-adrenergic receptor". Mol. Pharmacol. 48 (3): 492–8. PMID 7565630.
• Rodriguez M, Carillon C, Coquerel A, Le Fur G, Ferrara P, Caput D, Shire D (1995). "Evidence for the presence of beta 3-adrenergic receptor mRNA in the human brain". Brain Res. Mol. Brain Res. 29 (2): 369–75. doi:10.1016/0169-328X(94)00274-I. PMID 7609625.
• Clément K, Vaisse C, Manning BS, Basdevant A, Guy-Grand B, Ruiz J, Silver KD, Shuldiner AR, Froguel P, Strosberg AD (1995). "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. doi:10.1056/NEJM199508103330605. PMID 7609752.
• Dib A, Adélaïde J, Chaffanet M, Imbert A, Le Paslier D, Jacquemier J, Gaudray P, Theillet C, Birnbaum D, Pébusque MJ (1995). "Characterization of the region of the short arm of chromosome 8 amplified in breast carcinoma". Oncogene. 10 (5): 995–1001. PMID 7898940.
• Mahmoudian M (1994). "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. doi:10.1016/0263-7855(94)80004-9. PMID 8011597.
• Wilkie TM, Chen Y, Gilbert DJ, Moore KJ, Yu L, Simon MI, Copeland NG, Jenkins NA (1994). "Identification, chromosomal location, and genome organization of mammalian G-protein-coupled receptors". Genomics. 18 (2): 175–84. doi:10.1006/geno.1993.1452. PMID 8288218.
• Krief S, Lönnqvist F, Raimbault S, Baude B, Van Spronsen A, Arner P, Strosberg AD, Ricquier D, Emorine LJ (1993). "Tissue distribution of beta 3-adrenergic receptor mRNA in man". J. Clin. Invest. 91 (1): 344–9. doi:10.1172/JCI116191. PMC 330032. PMID 8380813.
• van Spronsen A, Nahmias C, Krief S, Briend-Sutren MM, Strosberg AD, Emorine LJ (1993). "The promoter and intron/exon structure of the human and mouse beta 3-adrenergic-receptor genes". Eur. J. Biochem. 213 (3): 1117–24. doi:10.1111/j.1432-1033.1993.tb17861.x. PMID 8389293.
• Lelias JM, Kaghad M, Rodriguez M, Chalon P, Bonnin J, Dupre I, Delpech B, Bensaid M, LeFur G, Ferrara P (1993). "Molecular cloning of a human beta 3-adrenergic receptor cDNA". FEBS Lett. 324 (2): 127–30. doi:10.1016/0014-5793(93)81377-C. PMID 8389717. S2CID 84702667.
• Candelore MR, Deng L, Tota LM, Kelly LJ, Cascieri MA, Strader CD (1996). "Pharmacological characterization of a recently described human beta 3-adrenergic receptor mutant". Endocrinology. 137 (6): 2638–41. doi:10.1210/endo.137.6.8641219. PMID 8641219.
• Fujisawa T, Ikegami H, Yamato E, Takekawa K, Nakagawa Y, Hamada Y, Oga T, Ueda H, Shintani M, Fukuda M, Ogihara T (1996). "Association of Trp64Arg mutation of the beta3-adrenergic-receptor with NIDDM and body weight gain". Diabetologia. 39 (3): 349–52. doi:10.1007/BF00418352. PMID 8721782. S2CID 24270803.
• Higashi K, Ishikawa T, Ito T, Yonemura A, Shige H, Nakamura H (1997). "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. doi:10.1006/bbrc.1997.6339. PMID 9126344.
• Hoffstedt J, Poirier O, Thörne A, Lönnqvist F, Herrmann SM, Cambien F, Arner P (1999). "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. doi:10.2337/diabetes.48.1.203. PMID 9892244.
• Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A (1999). "Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis". Nat. Genet. 22 (3): 239–47. doi:10.1038/10297. PMID 10391210. S2CID 4636523.
• Kimura K, Sasaki N, Asano A, Mizukami J, Kayahashi S, Kawada T, Fushiki T, Morimatsu M, Yoshida T, Saito M (2000). "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. doi:10.1055/s-2007-978597. PMID 10786926. S2CID 260166451.
• Cao W, Luttrell LM, Medvedev AV, Pierce KL, Daniel KW, Dixon TM, Lefkowitz RJ, Collins S (2001). "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. doi:10.1074/jbc.C000592200. PMID 11013230.
• Russell ST, Hirai K, Tisdale MJ (2002). "Role of β3-adrenergic receptors in the action of a tumour lipid mobilizing factor". Br. J. Cancer. 86 (3): 424–8. doi:10.1038/sj.bjc.6600086. PMC 2375201. PMID 11875710.

External links

• "β₃-adrenoceptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 30 December 2014. Retrieved 25 November 2008.
• Human ADRB3 genome location and ADRB3 gene details page in the UCSC Genome Browser.