Beta-3 adrenergic receptor

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)
End	37,966,599 bp
Gene location (Mouse)
Chr.	Chromosome 8 (mouse)
End	27,250,616 bp
RNA expression pattern
	Top expressed in
	Top expressed in
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function
Cellular component
Biological process
	Sources:Amigo / QuickGO
Orthologs
	155
	11556
	ENSG00000188778
	ENSMUSG00000031489
	P13945
	P25962
	NM_000025
	NM_013462
	NP_000016
	NP_038490
	Wikidata
View/Edit Human	View/Edit Mouse

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]

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]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000188778 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000031489 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: ADRB3 adrenergic, beta-3-, receptor".
^ 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
^ 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.
^ 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. S2CID 35026036.
^ 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.
^ 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.
^ ^a ^b ^c 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.
^ 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.

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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000188778 – Ensembl, May 2017

[refGRCm38Ensembl-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.

[entrez-5] "Entrez Gene: ADRB3 adrenergic, beta-3-, receptor".

[pmid15935402-6] 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.

[Rang163-7] Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 163

[pmid16457637-8] 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.

[pmid17669397-9] 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.

[pmid18358519-10] 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.

[pmid30892909-11] 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.

[pmid10411574-13] 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.

[pmid12324291-14] 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.

[pmid17626794-17] 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.

[pmid17626795-18] 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.

[pmid8569714-19] 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.

[pmid19422394-20] 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.

[pmid11013230-21] 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.

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