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 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
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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

Approved for clinical use

• Mirabegron (YM-178),^[9] approved for treatment of overactive bladder in Japan, United States, UK, Canada, China and India.
• Nebivolol^[10] selective beta(1)-blocker and beta(3)-agonist.
• Vibegron (MK-4618)^[11]

Experimental

• Amibegron (SR-58611A)^[12][13]
• BRL-37344^[14]
• CL-316,243^[15]
• L-742,791^[16]
• L-796,568^[17]
• LY-368,842
• Ro40-2148
• Solabegron (GW-427,353)^[18]

Antagonists

• L-748,328^[16]
• L-748,337^[16]
• 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