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β3-adrenoceptor

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Target id: 30

Nomenclature: β3-adrenoceptor

Family: Adrenoceptors

Contents:

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 408 8p11.23 ADRB3 adrenoceptor beta 3 29,53
Mouse 7 400 8 15.94 cM Adrb3 adrenergic receptor, beta 3 64
Rat 7 400 16q12.3 Adrb3 adrenoceptor beta 3 36,61
Previous and Unofficial Names Click here for help
atypical β-adrenoceptor | ADRB | beta-3 adrenoreceptor | Adrb-3 | beta 3-AR | beta3-adrenergic receptor | adrenergic receptor
Database Links Click here for help
Specialist databases
GPCRdb adrb3_human (Hs), adrb3_mouse (Mm), adrb3_rat (Rn)
Other databases
Alphafold P13945 (Hs), P25962 (Mm), P26255 (Rn)
ChEMBL Target CHEMBL246 (Hs), CHEMBL4030 (Mm), CHEMBL4031 (Rn)
DrugBank Target P13945 (Hs)
Ensembl Gene ENSG00000188778 (Hs), ENSMUSG00000031489 (Mm), ENSRNOG00000012674 (Rn)
Entrez Gene 155 (Hs), 11556 (Mm), 25645 (Rn)
Human Protein Atlas ENSG00000188778 (Hs)
KEGG Gene hsa:155 (Hs), mmu:11556 (Mm), rno:25645 (Rn)
OMIM 109691 (Hs)
Pharos P13945 (Hs)
RefSeq Nucleotide NM_000025 (Hs), NM_013462 (Mm), NM_013108 (Rn)
RefSeq Protein NP_000016 (Hs), NP_038490 (Mm), NP_037240 (Rn)
UniProtKB P13945 (Hs), P25962 (Mm), P26255 (Rn)
Wikipedia ADRB3 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Dog β3-adrenoceptor bound to mirabegron in complex with a miniGs heterotrimer.
PDB Id:  7DH5
Ligand:  mirabegron
Resolution:  3.16Å
Species:  Dog
References:  63
Associated Proteins Click here for help
Interacting Proteins
Name Effect References
β3-adrenoceptor 12
β2-adrenoceptor 12
c-Src ERK activation 16
Natural/Endogenous Ligands Click here for help
(-)-adrenaline
(-)-noradrenaline
Potency order of endogenous ligands (Human)
(-)-noradrenaline = (-)-adrenaline

Download all structure-activity data for this target as a CSV file go icon to follow link

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]ICYP Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Partial agonist 9.2 – 9.8 pKd 56,60,70,79,85
⤷ pKd 9.2 – 9.8 (Kd 6.31x10-10 – 1.58x10-10 M) [56,60,70,79,85]
[125I]ICYP Small molecule or natural product Ligand is labelled Ligand is radioactive Mm Partial agonist 9.3 – 9.4 pKd 70
⤷ pKd 9.3 – 9.4 [70]
[125I]ICYP Small molecule or natural product Ligand is labelled Ligand is radioactive Rn Partial agonist 9.2 pKd 70
⤷ pKd 9.2 [70]
[3H]CGP12177 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Partial agonist 7.0 pKd 5
⤷ pKd 7.0 [5]
carazolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 8.4 pKi 5
⤷ pKi 8.4 (Ki 1.99x10-9 M) [5]
carazolol Small molecule or natural product Approved drug Mm Full agonist 7.7 pKi 62
⤷ pKi 7.7 [62]
carazolol Small molecule or natural product Approved drug Rn Full agonist 7.7 pKi 62
⤷ pKi 7.7 [62]
CGP 12177 Small molecule or natural product Mm Partial agonist 6.8 pKi 62
⤷ pKi 6.8 [62]
CGP 12177 Small molecule or natural product Rn Partial agonist 6.8 pKi 62
⤷ pKi 6.8 [62]
CGP 12177 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 6.1 – 7.3 pKi 10,56,60,62
⤷ pKi 6.1 – 7.3 (Ki 7.94x10-7 – 5.01x10-8 M) [10,56,60,62]
BRL 37344 Small molecule or natural product Click here for species-specific activity table Hs Full agonist 6.4 – 7.0 pKi 10,27,40,62
⤷ pKi 6.4 – 7.0 (Ki 3.98x10-7 – 1x10-7 M) [10,27,40,62]
BRL 37344 Small molecule or natural product Mm Full agonist 6.5 pKi 62
⤷ pKi 6.5 [62]
BRL 37344 Small molecule or natural product Rn Full agonist 6.5 pKi 62
⤷ pKi 6.5 [62]
CL316243 Small molecule or natural product Mm Agonist 5.9 pKi 76
⤷ pKi 5.9 binding [76]
isoprenaline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 5.1 – 6.2 pKi 5,40,60,62,70,79,85
⤷ pKi 5.1 – 6.2 [5,40,60,62,70,79,85]
(-)-noradrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Hs Full agonist 4.7 – 6.3 pKi 40,70,85
⤷ pKi 4.7 – 6.3 [40,70,85]
fenoterol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 5.4 pKi 5
⤷ pKi 5.4 [5]
(±)-adrenaline Small molecule or natural product Ligand is endogenous in the given species Mm Full agonist 5.3 pKi 62
⤷ pKi 5.3 [62]
(±)-adrenaline Small molecule or natural product Ligand is endogenous in the given species Rn Full agonist 5.3 pKi 62
⤷ pKi 5.3 [62]
isoprenaline Small molecule or natural product Approved drug Rn Full agonist 5.3 pKi 62
⤷ pKi 5.3 [62]
cimaterol Small molecule or natural product Click here for species-specific activity table Hs Full agonist 5.3 pKi 5
⤷ pKi 5.3 [5]
amibegron Small molecule or natural product Hs Full agonist 5.2 pKi 10
⤷ pKi 5.2 [10]
CL316243 Small molecule or natural product Hs Agonist 5.2 pKi 101
⤷ pKi 5.2 [101]
isoprenaline Small molecule or natural product Approved drug Mm Full agonist 4.2 – 5.3 pKi 62,70
⤷ pKi 4.2 – 5.3 [62,70]
(-)-adrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 3.9 – 4.7 pKi 5,40
⤷ pKi 3.9 – 4.7 [5,40]
(±)-adrenaline Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 3.9 – 4.7 pKi 10,40,62
⤷ pKi 3.9 – 4.7 [10,40,62]
(-)-noradrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand is endogenous in the given species Ligand has a PDB structure Rn Full agonist 4.2 pKi 70
⤷ pKi 4.2 [70]
(-)-noradrenaline Small molecule or natural product Approved drug Ligand is endogenous in the given species Ligand has a PDB structure Mm Full agonist 3.8 pKi 70
⤷ pKi 3.8 [70]
L 755507 Small molecule or natural product Hs Full agonist 10.1 pEC50 5
⤷ pEC50 10.1 [5]
CL316243 Small molecule or natural product Mm Agonist 8.7 – 9.8 pEC50 44,76
⤷ pEC50 8.7 – 9.8 cAMP accumulation [44,76]
vibegron Small molecule or natural product Approved drug Monkey Agonist 9.2 pEC50 28
⤷ pEC50 9.2 (EC50 5.7x10-10 M) [28]
vibegron Small molecule or natural product Approved drug Primary target of this compound Hs Agonist 8.7 – 9.0 pEC50 14,26,28
⤷ pEC50 8.7 – 9.0 [14,26,28]
carazolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 8.8 pEC50 5
⤷ pEC50 8.8 [5]
L742791 Small molecule or natural product Hs Agonist 8.8 pEC50 100
⤷ pEC50 8.8 (EC50 1.6x10-9 M) [100]
solabegron Small molecule or natural product Primary target of this compound Click here for species-specific activity table Hs Agonist 8.4 – 8.7 pEC50 45,59,94
⤷ pEC50 8.4 – 8.7 [45,59,94]
L-748337 Small molecule or natural product Hs Partial agonist 8.4 pEC50 5
⤷ pEC50 8.4 [5]
mirabegron Small molecule or natural product Approved drug Ligand has a PDB structure Mm Agonist 7.3 – 9.3 pEC50 24
⤷ pEC50 8.3 – 9.3 [24]
pEC50 7.3 – 7.8 [24]
mirabegron Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 7.7 – 8.8 pEC50 14,24,38,88
⤷ pEC50 7.7 – 8.8 [14,24,38,88]
vibegron Small molecule or natural product Approved drug Clf Agonist 8.0 pEC50 28
⤷ pEC50 8.0 (EC50 1.1x10-8 M) [28]
mirabegron Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Agonist 7.7 pEC50 24
⤷ pEC50 7.7 [24]
fenoterol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 7.6 pEC50 5
⤷ pEC50 7.6 [5]
BRL 37344 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 7.5 pEC50 5
⤷ pEC50 7.5 [5]
isoprenaline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 7.4 pEC50 5
⤷ pEC50 7.4 [5]
(-)-noradrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Full agonist 7.2 pEC50 5
⤷ pEC50 7.2 [5]
SB251023 Small molecule or natural product Mm Agonist 7.1 pEC50 43
⤷ pEC50 7.1 [43]
vibegron Small molecule or natural product Approved drug Rn Agonist 7.1 pEC50 28
⤷ pEC50 7.1 (EC50 8.6x10-8 M) [28]
cimaterol Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.0 pEC50 5
⤷ pEC50 7.0 [5]
(-)-adrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Full agonist 6.5 pEC50 5
⤷ pEC50 6.5 [5]
abediterol Small molecule or natural product Click here for species-specific activity table Immunopharmacology Ligand Hs Agonist 5.5 pIC50 1
⤷ pIC50 5.5 (IC50 3.001x10-6 M) [1]
View species-specific agonist tables
Agonist Comments
The species orthologs of the human β-ARs found in the rat, mouse, and cow have significantly different agonist pharmacology that has proved problematic for drug development. For example, BRL37344 is a potent agonist at rodent β3-AR but a weak partial agonist at the human β3-AR [2] and carazolol has a much higher affinity for the bovine receptor [69], whereas [125I]CYP has lower affinity [85]. Carazolol is a potent high efficacy partial agonist at β3-AR but is also a potent partial agonist at β1-AR and a highly potent antagonist at β2-AR [5]. Agonist SB251023 has an pEC50 of 6.9 for the splice variant of the mouse β3 receptor, β3b [43]. For the agonist CL316243, a cAMP accumulation assay measured pEC50 values of 9.94 and 9.97 for the β3a and β3b splice variants respectively [78]. Although the human β3-AR has an intron no splice variants have been observed. The β3-AR has a more important physiological role in rodents than in humans. Since the β3-AR largely lacks sites required for receptor phosphorylation it is less susceptible to desensitisation than other β-AR subtypes. However, desensitisation can occur associated with mRNA and protein down regulation of receptor and post receptor signalling proteins and there is also evidence for cell specific events [66]. Ligands acting at β3-AR can also display ligand-directed signalling [76-77]. Vibegron, solabegron and mirabegron are selective β3-AR agonists that potently activate human β3-AR [45]. Clinical uses: β3-AR agonists are used to treat overactive bladder syndrome.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
L-748337 Small molecule or natural product Hs Antagonist 9.2 – 9.5 pKB 77
⤷ pKB 9.2 – 9.5 [77]
[3H]L748337 Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 8.4 – 8.7 pKd 96
⤷ pKd 8.4 – 8.7 [96]
carvedilol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.3 – 9.4 pKi 4,15
⤷ pKi 8.3 – 9.4 [4,15]
tertatolol Small molecule or natural product Hs Antagonist 8.6 pKi 70
⤷ pKi 8.6 [70]
L-748328 Small molecule or natural product Hs Antagonist 8.4 – 8.6 pKi 5,15
⤷ pKi 8.4 – 8.6 [5,15]
L-748337 Small molecule or natural product Hs Antagonist 8.0 – 8.4 pKi 5,15
⤷ pKi 8.0 – 8.4 [5,15]
SR59230A Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.9 – 8.4 pKi 5,15,23,40
⤷ pKi 6.9 – 8.4 [5,15,23,40]
pindolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 7.1 pKi 5
⤷ pKi 7.1 [5]
bupranolol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.8 – 7.3 pKi 10,15,56,62
⤷ pKi 6.8 – 7.3 [10,15,56,62]
tertatolol Small molecule or natural product Mm Antagonist 7.0 pKi 70
⤷ pKi 7.0 [70]
tertatolol Small molecule or natural product Rn Antagonist 7.0 pKi 70
⤷ pKi 7.0 [70]
bunolol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.8 pKi 70
⤷ pKi 6.8 (Ki 1.6x10-7 M) [70]
propranolol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.3 – 7.2 pKi 4,56,70
⤷ pKi 6.3 – 7.2 [4,56,70]
propranolol Small molecule or natural product Approved drug Mm Antagonist 6.5 – 6.6 pKi 70
⤷ pKi 6.5 – 6.6 [70]
propranolol Small molecule or natural product Approved drug Rn Antagonist 6.4 pKi 70
⤷ pKi 6.4 [70]
bunolol Small molecule or natural product Approved drug Rn Antagonist 6.4 pKi 70
⤷ pKi 6.4 [70]
nebivolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 5.7 – 7.0 pKi 5,33
⤷ pKi 5.7 – 7.0 [5,33]
Description: Radioligand binding
nadolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.2 – 6.3 pKi 4,15
⤷ pKi 6.2 – 6.3 [4,15]
bunolol Small molecule or natural product Approved drug Mm Antagonist 6.2 – 6.3 pKi 70
⤷ pKi 6.2 – 6.3 [70]
ICI 118551 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Antagonist 5.8 – 6.6 pKi 4,40,56,62
⤷ pKi 5.8 – 6.6 [4,40,56,62]
CGP 20712A Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.1 – 5.7 pKi 4,15,56,62
⤷ pKi 5.1 – 5.7 [4,15,56,62]
pindolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 5.6 – 7.4 pEC50 5
⤷ pEC50 5.6 – 7.4 [5]
View species-specific antagonist tables
Antagonist Comments
Many of the compounds listed as antagonists at the β3-AR can behave in some systems as agonists at the β3-AR. These include L748337, SR59230A, carvedilol, nadolol, tertatolol, pindolol and propranolol as well as compounds that exhibit similar behaviour at other β-AR subtypes, notably CGP12177, pindolol, cyanopindolol, labetalol and alprenolol [3,5,10-11,27,62,89]. The approved drug propranolol is primarily a β1-/β2-AR antagonist with lower affinity for β3-AR. SR59230A that is often described as a selective antagonist at β3-AR displays little selectivity and has similar potency at all 3 subtypes (in fact higher affinity at β2-AR) [5]- what it does have is reasonable potency at blocking β3-AR. L-748337 is currently the most selective antagonist at the human β3-AR [96]. The human β3-AR also appears to exist in two active conformations (see also β1-AR) with fenoterol stimulating responses via the catecholamine formation whereas alprenolol, SR58230A and CGP12177 utilise the secondary conformation [3]. Clinical uses: β3-AR antagonists are not used clinically.
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family
Comments:  Agonist stimulated Gs coupling leads to stimulation of adenylyl cyclase (AC) and causes the conversion of ATP into cAMP. This activates protein kinase A (PKA) that in adipocytes leads to phosphorylation and activation of the hormone sensitive lipase and perilipins. Other kinases including ERK1/2, p38MAPK and AMP kinases may also be activated and PKA may be involved. In other tissues such as gut cAMP generation leads to relaxation.
References:  18,22,51,73,82
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Guanylate cyclase stimulation
Comments:  β3-ARs can also couple to Gi to inhibit adenylyl cyclase activity and reduce cAMP levels in some systems. βγ subunits from Gi are also likely involved in ERK1/2 phosphorylation following β3-AR activation. β3-ARs can also stimulate nitric oxide production through the activation of endothelial nitric oxide synthase. Nitric oxide activates guanylyl cyclase and increases cGMP levels.
References:  22,30,37,54,73,93,97
Tissue Distribution Click here for help
Endothelium of coronary microarteries.
Species:  Human
Technique:  Immunohistochemistry.
References:  25
Brown adipose tissue.
Species:  Human
Technique:  PCR.
References:  53
Bladder.
Species:  Human
Technique:  Relaxation of bladder smooth muscle.
References:  75
Prostate.
Species:  Human
Technique:  RT-PCR and relaxation of prostate strips.
References:  87
Gall bladder > small intestine > stomach, prostate > adipose tissue > left atrium
Species:  Human
Technique:  RT-PCR and RNase protection assay.
References:  9,50
Bladder, gall bladder, brown adipose tissue.
Species:  Human
Technique:  RT-PCR.
References:  7
Brown adipose tissue.
Species:  Mouse
Technique:  [3H]2-deoxyglucose uptake.
References:  67
White adipose tissue, colon, ileum, cerebral cortex.
Species:  Rat
Technique:  RT-PCR.
References:  73
Internal anal sphincter (IAS) smooth muscle.
Species:  Rat
Technique:  Western blotting.
References:  54
Bladder.
Species:  Rat
Technique:  Relaxation of bladder smooth muscle.
References:  38,75
Adipose tissue.
Species:  Rat
Technique:  Northern blotting.
References:  36
Expression Datasets Click here for help

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays Click here for help
Measurement of cAMP levels in CHO-K1 cells stably transfected with the rat β3 receptor.
Species:  Rat
Tissue:  CHO-K1 cells.
Response measured:  cAMP accumulation.
References:  36
Measurement of cAMP levels in human immortalised preadipocytes (PAZ-6 cells) endogenously expressing the β3-adrenoceptor.
Species:  Human
Tissue:  PAZ-6 cells.
Response measured:  cAMP accumulation.
References:  104
Measurement of lypolysis (glycerol release) in human immortalised preadipocytes (PAZ-6 cells) endogenously expressing the β3-adrenoceptor.
Species:  Human
Tissue:  PAZ-6 cells.
Response measured:  Glycerol release.
References:  104
Measurement of cAMP levels in CHO cells stably transfected with the human β3 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  cAMP accumulation.
References:  5,29,40,60,62
Measurement of cAMP levels in mouse brown adipocytes in culture.
Species:  Mouse
Tissue:  Brown adipocytes in culture.
Response measured:  cAMP accumulation.
References:  18,24,47
Measurement of nitric oxide release (using diaminofluorescence) and signal transduction (using immunohistochemistry) in human myocardium.
Species:  Human
Tissue:  Myocardium.
Response measured:  NO release, eNOS activation.
References:  13
Presence of β3-AR in brown adipose tissue.
Species:  Mouse
Tissue:  Brown adipocytes in culture.
Response measured:  [3H]2-deoxyglucose uptake.
References:  67
Measurements in CHO cells stably transfected with the human β3 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  cAMP accumulation, ERK1/2 and p38MAPK phosphorylation.
References:  77
Measurement of cAMP levels in CHO cells stably transfected with the mouse β3-AR splice variants.
Species:  Mouse
Tissue:  CHO cells.
Response measured:  cAMP accumulation.
References:  43
Measurement of mechanical and electrical responses of endomyocardium.
Species:  Human
Tissue:  Endomyocardial biopsies obtained form the right interventricular septum.
Response measured:  Increase in peak tension and ecrease in amplitude of the action potential and acceleration of the repolarisation phase when exposed to β3-AR agonists..
References:  34
Measurement of glucose uptake in brown adipocytes in culture.
Species:  Mouse
Tissue:  Brown adipocytes in culture.
Response measured:  [3H] 2 deoxy glucose uptake.
References:  67
Physiological Functions Click here for help
Lipolysis (glycerol release).
Species:  Mouse
Tissue:  3T3-F442A-derived adipocytes.
References:  62
Lipolysis (glycerol release).
Species:  Rat
Tissue:  White adipocytes.
References:  35
Relaxation of rat abdominal aorta smooth muscle.
Species:  Rat
Tissue:  Abdominal aorta smooth muscle.
References:  57
Glucose uptake.
Species:  Mouse
Tissue:  Brown adipocytes in culture.
References:  18
All of the β-adrenoceptors cause relaxation of the internal anal sphincter (IAS).
Species:  Rat
Tissue:  Internal anal sphincter (IAS).
References:  54
Relaxation of colon and oesophagus.
Species:  Mouse
Tissue:  Colon, oesophagus.
References:  68
Negative inotropic effect.
Species:  Human
Tissue:  Heart.
References:  34
Relaxation.
Species:  Human
Tissue:  Myometrium.
References:  74
Decrease in gastrointestinal motility.
Species:  Mouse
Tissue:  Small intestine and stomach.
References:  32
Vasodilatation via nitric oxide and vessel hyperpolarisation.
Species:  Human
Tissue:  Coronary resistance arteries.
References:  25
Lipolysis, thermogenesis.
Species:  Human
Tissue:  Brown fat.
References:  7,17,46
Lipolysis.
Species:  Human
Tissue:  White fat.
References:  7,55,90
Relaxation.
Species:  Human
Tissue:  Smooth muscle cells isolated from the colon.
References:  6,80
Relaxation of taenia coli.
Species:  Human
Tissue:  Taenia coli.
References:  72
Relaxation of ileum.
Species:  Rat
Tissue:  Ileum.
References:  73
Bladder relaxation.
Species:  Human
Tissue:  Urinary bladder.
References:  7,75
Gall bladder relaxation.
Species:  Human
Tissue:  Gall bladder.
References:  7
Lipolysis, thermogenesis.
Species:  Mouse
Tissue:  Brown fat.
References:  8
Memory consolidation.
Species:  Mouse
Tissue:  Brain.
References:  84
Physiological Consequences of Altering Gene Expression Click here for help
Cadiac overexpression of the human β3-adrenoceptor results in positive inotropy.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  49
Cardiac specific overexpression of the mouse β3-adrenoceptor produces the same negative inotropic effects as seen in human ventricular tissue.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  91
In β3-adrenoceptor knockout mice, activation of β1 receptors compensates for the lack of β3 receptor and causes relaxation of colon and oesophagus muscle, as in the wild-type.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  68
β3-adrenoceptor knockout mice exhibit the same amount of glucose uptake as wildtype mice, showing that the β1 receptor (and to a smaller degree the α1-adrenoceptor) functionally compensates for the lack of β3 receptors, despite there being no change in β1 or α1 gene expression.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  19
Cardiac β3-AR protect from fibrosis in response to haemodynamic stress by modulating nitric oxide and oxidant stress-dependent paracrine signaling to fibroblasts.
Species:  Mouse
Tissue:  Heart.
Technique:  Myocyte-specific expression of β3-AR or tamoxifen-inducible homozygous deletion (c-Adrb3-ko).
References:  39
Memory consolidation.
Species:  Mouse
Tissue:  Brain.
Technique:  Gene targeting in embryonic stem cells.
References:  84
β3-adrenoceptor knockout mice exhibit a complete loss of β3 agonist-induced adenylyl cyclase activity and lipolysis. They also have an increase in fat storage, suggesting that the β3 subtype has a role in energy balance regulation. There appears to be cross-talk between β1 and β3 gene expression, shown by an upregulation of β1 receptor expression in white and brown adipose tissue of knockout mice.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  86
β3-AR knockout mice display a loss of metabolic effects to the β3-AR agonist mirabegron.
Species:  Mouse
Tissue:  Brown and brite adipocytes.
Technique:  Gene targeting in embryonic stem cells.
References:  24
Phenotypes, Alleles and Disease Models Click here for help Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0001777 abnormal body temperature regulation PMID: 12161655 
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0002971 abnormal brown adipose tissue morphology PMID: 12161655 
Adrb3tm1Lowl Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S4/SvJae * FVB/N		 MGI:87939  MP:0008872 abnormal physiological response to xenobiotic PMID: 7493988 
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0005290 decreased oxygen consumption PMID: 12161655 
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0001260 increased body weight PMID: 12161655 
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0009119 increased brown fat cell size PMID: 12161655 
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0005669 increased circulating leptin level PMID: 12161655 
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0009294 increased interscapular fat pad weight PMID: 12161655 
Adrb3tm1Lowl Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S4/SvJae * FVB/N		 MGI:87939  MP:0009300 increased parametrial fat pad weight PMID: 7493988 
Adrb3tm1Jpg Adrb3tm1Jpg/Adrb3tm1Jpg
involves: 129S4/SvJae * C57BL/6J		 MGI:87939  MP:0005458 increased percent body fat PMID: 9276726 
Adrb3tm1Jpg Adrb3tm1Jpg/Adrb3tm1Jpg
involves: 129S4/SvJae * C57BL/6J		 MGI:87939  MP:0005455 increased susceptibility to weight gain PMID: 9276726 
Adrb3tm1Lowl Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S4/SvJae * FVB/N		 MGI:87939  MP:0010024 increased total body fat amount PMID: 7493988 
Adrb3tm1Jpg Adrb3tm1Jpg/Adrb3tm1Jpg
involves: 129S4/SvJae * C57BL/6J		 MGI:87939  MP:0010024 increased total body fat amount PMID: 9276726 
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0010024 increased total body fat amount PMID: 12161655 
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0001261 obese PMID: 12161655 
Adrb3tm1Jpg Adrb3tm1Jpg/Adrb3tm1Jpg
involves: 129S4/SvJae * C57BL/6J		 MGI:87939  MP:0001433 polyphagia PMID: 9276726 
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Trp64 -> Arg polymorphism is associated with impaired insulin secretion.
References:  20
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Trp64 -> Arg polymorphism is associated with earlier onset of non-insulin-dependent diabetes mellitus and reduced metabolic rate.
References:  98
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Trp64 -> Arg polymorphism is associated with hypertension.
References:  92
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Trp64 -> Arg polymorphism is associated with a lower resting autonomic nervous system activity.
References:  81
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Trp64 -> Arg polymorphism is associated with mild gestational diabetes mellitus.
References:  31
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Trp64 -> Arg polymorphism is associated with an increased sensitivity to noradrenaline and an influence on blood triacylglycerol levels.
References:  58
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Trp64 -> Arg polymorphism is associated with insulin resistance.
References:  99
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Trp64 -> Arg polymorphism is associated with accelerated age-related decreases in BAT activity.
References:  102
Type:  Single nucleotide polymorphism
Species:  Human
Description:  A Trp64 -> Arg single nucleotide polymorphism has been identified in humans.
The major consequence of this natural mutation is the reduced lipolytic activity and subsequent association with an increased obesity risk.
Some papers report no effect on lypolytic activity (see reference 211).
Reference 279 reports the interation between this β3-adrenoceptor polymorphism and the Pro12 -> Ala polymorphism of PPARγ2.
References:  21,48,65,71,83,95,103
Type:  Single nucleotide polymorphism
Species:  Human
Description:  Two novelβ3-AR (ADRB3) gene polymorphisms (Ser165Pro and Ser257Pro) are associated with type 2 diabetes (T2DM) in the Chinese population.
References:  42
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Trp64 -> Arg polymorphism is weakly associated with over-active bladder syndrome.
References:  41
General Comments
For a review on the β-adrenoceptor polymorphisms see reference [52], however it should be noted that many of the reported polymorphisms associated with obesity and diabetes have not been consistently reproduced.

References

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