Beta-3 adrenergic receptor

Adrenoceptor beta 3

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
2CDW

Identifiers

Symbols

ADRB3 ; BETA3AR

External IDs

OMIM: 109691 MGI: 87939 HomoloGene: 37250 IUPHAR: 30 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 component of plasma membrane • receptor complex
Biological process	• temperature homeostasis • 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 • activation of adenylate cyclase activity • cell-cell signaling • aging • response to cold • heat generation • negative regulation of multicellular organism growth • eating behavior • positive regulation of MAPK cascade • response to antibiotic • brown fat cell differentiation • adenylate cyclase-activating adrenergic receptor signaling pathway
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

155

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 8:
37.96 – 37.97 Mb

Chr 8:
27.23 – 27.23 Mb

PubMed search

The beta-3 adrenergic receptor (β₃ adrenoreceptor), 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 G_s.^[1]

Ligands

Agonists

Amibegron (SR-58611A)^[5]^[6]
CL-316,243^[7]
L-742,791^[8]
L-796,568^[9]
LY-368,842
Mirabegron (YM-178),^[10] approved for treatment of overactive bladder in Japan, United States, UK, Canada, China and India.
Ro40-2148
Solabegron (GW-427,353)^[11]
Vibegron (MK-4618)^[12]

Antagonists

L-748,328^[8]
L-748,337^[8]
SR 59230A was thought to be a selective β₃ antagonist^[13] but later found to also be an antagonist of the α₁ receptor.^[14]

Interactions

Beta-3 adrenergic receptor has been shown to interact with Src.^[15]

References

1 2 "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.
↑ 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.
1 2 3 Candelore MR, Deng L, Tota L, Guan XM, Amend A, Liu Y, Newbold R, Cascieri MA, Weber AE (Aug 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. PMID 12324291.
↑ 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.
↑ 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.
↑ 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.

Cell surface receptor: G protein-coupled receptors

Class A: Rhodopsin like

Neurotransmitter

Adrenergic	α1 (A B D) α2 (A B C) β1 β2 β3

Purinergic	Adenosine (A1 A2A A2B A3) P2Y (1 2 4 5 6 8 9 10 11 12 13 14)

Serotonin	(all but 5-HT3) 5-HT1 (A B D E F) 5-HT2 (A B C) 5-HT (4 5A 6 7)

Other	Acetylcholine (M1 M2 M3 M4 M5) Dopamine (D1 D2 D3 D4 D5) Histamine (H1 H2 H3 H4) Melatonin (1A 1B 1C) TAAR (1 2 3 5 6 8 9)

Metabolites and
signaling molecules

Eicosanoid	CysLT (1 2) LTB4 (1 2) FPRL1 OXE Prostaglandin (DP (1 2), EP (1 2 3 4), FP) Prostacyclin Thromboxane

Other	Bile acid Cannabinoid (CB1 CB2, GPR (18 55 119)) EBI2 Estrogen Free fatty acid (1 2 3 4) Lactate Lysophosphatidic acid (1 2 3 4 5 6) Lysophospholipid (1 2 3 4 5 6 7 8) Niacin (1 2) Oxoglutarate PAF Sphingosine-1-phosphate (1 2 3 4 5) Succinate

Peptide

Neuropeptide	B/W (1 2) FF (1 2) S Y (1 2 4 5) Neuromedin (B U (1 2)) Neurotensin (1 2)

Other	Anaphylatoxin (C3a C5a) Angiotensin (1 2) Apelin Bombesin (BRS3 GRPR NMBR) Bradykinin (B1 B2) Chemokine Cholecystokinin (A B) Endothelin (A B) Formyl peptide (1 2 3) FSH Galanin (1 2 3) GHB receptor Gonadotropin-releasing hormone (1 2) Ghrelin Kisspeptin Luteinizing hormone/choriogonadotropin MAS (1 1L D E F G X1 X2 X3 X4) Melanocortin (1 2 3 4 5) MCHR (1 2) Motilin Opioid (Delta Kappa Mu Nociceptin & Zeta, but not Sigma) Orexin (1 2) Oxytocin Prokineticin (1 2) Prolactin-releasing peptide Relaxin (1 2 3 4) Somatostatin (1 2 3 4 5) Tachykinin (1 2 3) Thyrotropin Thyrotropin-releasing hormone Urotensin-II Vasopressin (1A 1B 2)

Miscellaneous

Orphan	GPR (1 3 4 6 12 15 17 18 19 20 21 22 23 25 26 27 31 32 33 34 35 37 39 42 44 45 50 52 55 61 62 63 65 68 75 77 78 81 82 83 84 85 87 88 92 101 103 109A 109B 119 120 132 135 137B 139 141 142 146 148 149 150 151 152 153 160 161 162 171 173 174 176 177 182 183)

Other	Adrenomedullin Olfactory Opsin (3 4 5 1LW 1MW 1SW RGR RRH) Protease-activated (1 2 3 4) SREB (1 2 3)

Class B: Secretin like

Adhesion	ADGRG (1 2 3 4 5 6 7)

Orphan	GPR (56 64 97 98 110 111 112 113 114 115 116 123 124 125 126 128 133 143 144 155 157)

Other	Brain-specific angiogenesis inhibitor (1 2 3) Cadherin (1 2 3) Calcitonin CALCRL CD97 Corticotropin-releasing hormone (1 2) EMR (1 2 3) Glucagon (GR GIPR GLP1R GLP2R) Growth hormone releasing hormone PACAPR1 GPR Latrophilin (1 2 3 ELTD1) Methuselah-like proteins Parathyroid hormone (1 2) Secretin Vasoactive intestinal peptide (1 2)

Class C: Metabotropic glutamate / pheromone

Taste	TAS1R (1 2 3) TAS2R (1 3 4 5 7 8 9 10 13 14 16 19 20 30 31 38 39 40 41 42 43 45 46 50 60)

Other	Calcium-sensing receptor GABA B (1 2) Glutamate receptor (Metabotropic glutamate (1 2 3 4 5 6 7 8)) GPRC6A GPR (156 158 179) RAIG (1 2 3 4)

Class F: Frizzled / Smoothened

Frizzled	Frizzled (1 2 3 4 5 6 7 8 9 10)

Smoothened	Smoothened

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