Beta-3 adrenergic receptor

Adrenoceptor beta 3
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	2CDW
Identifiers
Symbols	ADRB3; BETA3AR
External IDs	OMIM: 109691 MGI: 87939 HomoloGene: 37250 IUPHAR: β3-adrenoceptor ChEMBL: 246 GeneCards: ADRB3 Gene
Gene Ontology
Molecular function	• beta-adrenergic receptor activity; • protein binding; • beta3-adrenergic receptor activity; • beta-3 adrenergic receptor binding; • protein homodimerization activity; • epinephrine binding; • norepinephrine binding;
Cellular component	• nucleus; • plasma membrane; • integral to plasma membrane; • receptor complex;
Biological process	• diet induced thermogenesis; • vasodilation by norepinephrine-epinephrine involved in regulation of systemic arterial blood pressure; • desensitization of G-protein coupled receptor protein signaling pathway by arrestin; • carbohydrate metabolic process; • generation of precursor metabolites and energy; • energy reserve metabolic process; • receptor-mediated endocytosis; • G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger; • adenylate cyclase-modulating G-protein coupled receptor signaling pathway; • adenylate cyclase-activating G-protein coupled receptor signaling pathway; • activation of adenylate cyclase activity; • aging; • response to cold; • heat generation; • negative regulation of multicellular organism growth; • eating behavior; • positive regulation of MAPK cascade; • brown fat cell differentiation;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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The beta-3 adrenergic receptor (β₃ adrenoreceptor), also known as ADRB3, is an beta-adrenergic receptor, and also denotes the human gene encoding it.^[1]

[edit] 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 CNS. Beta3-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]

[edit] 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.^[1]

[edit] Agonists

Mirabegron (YM-178),^[5] approved for treatment of overactive bladder in Japan and the United States.

Amibegron (SR-58611A)^[6]^[7]

Solabegron (GW-427,353)^[8]

L-796,568^[9]
CL-316,243^[10]
LY-368,842
Ro40-2148

A selective β₃ agonist has potential weight loss effects through modulation of lipolysis.^[2]

[edit] Antagonists

SR 59230A was thought to be a selective β₃ antagonist^[11] but later found to also be an antagonist of the α₁ receptor.^[12]

[edit] See also

Other adrenergic receptors

[edit] Interactions

Beta-3 adrenergic receptor has been shown to interact with Src.^[13]

[edit] References

^ ^a ^b "Entrez Gene: ADRB1 adrenergic, beta-1-, receptor". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=153.
^ ^a ^b 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.
^ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 163
^ Masaaki Sawa, Hiroshi Harada (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.
^ Gras, J (2012). "Mirabegron for the treatment of overactive bladder". Drugs of today (Barcelona, Spain : 1998) 48 (1): 25–32. doi:10.1358/dot.2012.48.1.1738056. PMID 22384458.
^ 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.
^ 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.
^ 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.
^ 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. PMID 12324291.
^ 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.
^ 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.
^ 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2795232/.
^ Cao, W; Luttrell L M, Medvedev A V, Pierce K L, Daniel K W, Dixon T M, Lefkowitz R J, Collins S (December 2000). "Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activation". J. Biol. Chem. (UNITED STATES) 275 (49): 38131–4. doi:10.1074/jbc.C000592200. ISSN 0021-9258. PMID 11013230.

[edit] 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.

[edit] 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 et al. (1991). "Molecular characterization of the mouse beta 3-adrenergic receptor: relationship with the atypical receptor of adipocytes". EMBO J. 10 (12): 3721–7. PMC 453106. PMID 1718744. //www.ncbi.nlm.nih.gov/pmc/articles/PMC453106/.
Emorine LJ, Marullo S, Briend-Sutren MM et al. (1989). "Molecular characterization of the human beta 3-adrenergic receptor". Science 245 (4922): 1118–21. 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 et al. (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 et al. (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 et al. (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 et al. (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 et al. (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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC330032/.
van Spronsen A, Nahmias C, Krief S et al. (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 et al. (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.
Candelore MR, Deng L, Tota LM et al. (1996). "Pharmacological characterization of a recently described human beta 3-adrenergic receptor mutant". Endocrinology 137 (6): 2638–41. doi:10.1210/en.137.6.2638. PMID 8641219.
Fujisawa T, Ikegami H, Yamato E et al. (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.
Higashi K, Ishikawa T, Ito T et al. (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 et al. (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 et al. (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.
Kimura K, Sasaki N, Asano A et al. (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.
Cao W, Luttrell LM, Medvedev AV et al. (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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2375201/.

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[entrez-1] "Entrez Gene: ADRB1 adrenergic, beta-1-, receptor". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=153.

[pmid15935402-2] 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.

[Rang163-3] Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 163

[pmid16457637-4] Masaaki Sawa, Hiroshi Harada (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.

[5] Gras, J (2012). "Mirabegron for the treatment of overactive bladder". Drugs of today (Barcelona, Spain : 1998) 48 (1): 25–32. doi:10.1358/dot.2012.48.1.1738056. PMID 22384458.

[pmid17669397-6] 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.

[pmid18358519-7] 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.

[pmid17626794-8] 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.

[pmid12324291-9] 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. PMID 12324291.

[10] 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.

[pmid8569714-11] 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.

[pmid19422394-12] 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. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2795232/.

[pmid11013230-13] Cao, W; Luttrell L M, Medvedev A V, Pierce K L, Daniel K W, Dixon T M, Lefkowitz R J, Collins S (December 2000). "Direct binding of activated c-Src to the beta 3-adrenergic receptor is required for MAP kinase activation". J. Biol. Chem. (UNITED STATES) 275 (49): 38131–4. doi:10.1074/jbc.C000592200. ISSN 0021-9258. PMID 11013230.

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Beta-3 adrenergic receptor

Contents

[edit] Function

[edit] Mechanism of action

[edit] Agonists

[edit] Antagonists

[edit] See also

[edit] Interactions

[edit] References

[edit] External links

[edit] Further reading

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