β<sub>3</sub>-adrenoceptor | Adrenoceptors | IUPHAR/BPS Guide to PHARMACOLOGY

β3-adrenoceptor

Target id: 30

Nomenclature: β3-adrenoceptor

Family: Adrenoceptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: OFF :     Currently no data for β3-adrenoceptor in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 408 8p12-p11.2 ADRB3 adrenoceptor beta 3 18,33
Mouse 7 400 8 A2-A4 Adrb3 adrenergic receptor, beta 3 42
Rat 7 400 16q12.3 Adrb3 adrenoceptor beta 3 23,41
Previous and Unofficial Names
atypical β-adrenoceptor | ADRB | beta-3 adrenoreceptor | Adrb-3 | beta 3-AR | beta3-adrenergic receptor | adrenergic receptor
Database Links
Specialist databases
GPCRDB adrb3_human (Hs), adrb3_mouse (Mm), adrb3_rat (Rn)
Other databases
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Associated Proteins
Interacting Proteins
Name Effect References
β3-adrenoceptor 8
β2-adrenoceptor 8
Natural/Endogenous Ligands
(-)-adrenaline
(-)-noradrenaline
Potency order of endogenous ligands (Human)
(-)-noradrenaline = (-)-adrenaline

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]ICYP Hs Partial agonist 9.2 – 9.8 pKd 36,40,46,51,56
pKd 9.2 – 9.8 (Kd 6.31x10-10 – 1.58x10-10 M) [36,40,46,51,56]
[125I]ICYP Mm Partial agonist 9.3 – 9.4 pKd 46
pKd 9.3 – 9.4 [46]
[125I]ICYP Rn Partial agonist 9.2 pKd 46
pKd 9.2 [46]
carazolol Hs Full agonist 8.7 pKi 38
pKi 8.7 (Ki 1.99x10-9 M) [38]
carazolol Mm Full agonist 7.7 pKi 38
pKi 7.7 [38]
carazolol Rn Full agonist 7.7 pKi 38
pKi 7.7 [38]
CGP 12177 Mm Partial agonist 6.8 pKi 38
pKi 6.8 [38]
CGP 12177 Rn Partial agonist 6.8 pKi 38
pKi 6.8 [38]
CGP 12177 Hs Partial agonist 6.1 – 7.3 pKi 6,36,38,40
pKi 6.1 – 7.3 (Ki 7.94x10-7 – 5.01x10-8 M) [6,36,38,40]
BRL 37344 Hs Full agonist 6.4 – 7.0 pKi 6,17,24,38
pKi 6.4 – 7.0 (Ki 3.98x10-7 – 1x10-7 M) [6,17,24,38]
BRL 37344 Mm Full agonist 6.5 pKi 38
pKi 6.5 [38]
BRL 37344 Rn Full agonist 6.5 pKi 38
pKi 6.5 [38]
CL316243 Mm Agonist 5.9 pKi 49
pKi 5.9 binding [49]
isoprenaline Hs Full agonist 5.1 – 6.2 pKi 24,38,40,46,51,56
pKi 5.1 – 6.2 [24,38,40,46,51,56]
(-)-noradrenaline Hs Full agonist 4.7 – 6.3 pKi 24,46,56
pKi 4.7 – 6.3 [24,46,56]
(±)-adrenaline Mm Full agonist 5.3 pKi 38
pKi 5.3 [38]
(±)-adrenaline Rn Full agonist 5.3 pKi 38
pKi 5.3 [38]
isoprenaline Rn Full agonist 5.3 pKi 38
pKi 5.3 [38]
amibegron Hs Full agonist 5.2 pKi 6
pKi 5.2 [6]
CL316243 Hs Agonist 5.2 pKi 69
pKi 5.2 [69]
isoprenaline Mm Full agonist 4.2 – 5.3 pKi 38,46
pKi 4.2 – 5.3 [38,46]
(±)-adrenaline Hs Full agonist 3.9 – 4.7 pKi 6,24,38
pKi 3.9 – 4.7 [6,24,38]
(-)-noradrenaline Rn Full agonist 4.2 pKi 46
pKi 4.2 [46]
(-)-adrenaline Hs Agonist 3.9 pKi 24
pKi 3.9 [24]
(-)-noradrenaline Mm Full agonist 3.8 pKi 46
pKi 3.8 [46]
L 755507 Hs Full agonist 10.1 pEC50 3
pEC50 10.1 [3]
CL316243 Mm Agonist 8.7 – 9.8 pEC50 26,49
pEC50 8.7 – 9.8 cAMP accumulation [26,49]
L742791 Hs Agonist 8.8 pEC50 68
pEC50 8.8 (EC50 1.6x10-9 M) [68]
solabegron Hs Agonist 8.4 pEC50 64
pEC50 8.4 [64]
mirabegron Hs Agonist 7.7 pEC50 58
pEC50 7.7 (EC50 2.24x10-8 M) [58]
SB251023 Mm Agonist 7.1 pEC50 25
pEC50 7.1 [25]
abediterol 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-adrenoceptors found in the rat, mouse, and cow have significantly different agonist pharmacology. For example, carazolol has a much higher affinity for the bovine receptor [45], whereas [125I]CYP has lower affinity [56]. Agonist SB251023 has an pEC50 of 6.9 for the splice variant of the mouse β3 receptor, β3b [25]. 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 [50].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
carvedilol Hs Antagonist 9.4 pKi 10
pKi 9.4 [10]
tertatolol Hs Antagonist 8.6 pKi 46
pKi 8.6 [46]
L748328 Hs Antagonist 8.4 pKi 10
pKi 8.4 (Ki 3.7x10-9 M) [10]
L-748337 Hs Antagonist 8.4 pKi 10
pKi 8.4 [10]
SR59230A Hs Antagonist 6.9 – 8.4 pKi 10,15,24
pKi 6.9 – 8.4 [10,15,24]
bupranolol Hs Antagonist 6.8 – 7.3 pKi 6,10,36,38
pKi 6.8 – 7.3 [6,10,36,38]
tertatolol Mm Antagonist 7.0 pKi 46
pKi 7.0 [46]
tertatolol Rn Antagonist 7.0 pKi 46
pKi 7.0 [46]
levobunolol Hs Antagonist 6.8 pKi 46
pKi 6.8 (Ki 1.6x10-7 M) [46]
propranolol Hs Antagonist 6.3 – 7.2 pKi 36,46
pKi 6.3 – 7.2 [36,46]
propranolol Mm Antagonist 6.5 – 6.6 pKi 46
pKi 6.5 – 6.6 [46]
propranolol Rn Antagonist 6.4 pKi 46
pKi 6.4 [46]
levobunolol Rn Antagonist 6.4 pKi 46
pKi 6.4 [46]
nadolol Hs Antagonist 6.3 pKi 10
pKi 6.3 [10]
levobunolol Mm Antagonist 6.2 – 6.3 pKi 46
pKi 6.2 – 6.3 [46]
ICI 118551 Hs Antagonist 5.8 – 6.6 pKi 2,24,36,38
pKi 5.8 – 6.6 [2,24,36,38]
CGP 20712A Hs Antagonist 5.1 – 5.7 pKi 2,10,36,38
pKi 5.1 – 5.7 [2,10,36,38]
View species-specific antagonist tables
Antagonist Comments
Nadolol, tertatolol and propranolol can behave in some systems as agonists instead of antagonists at the β3-adrenoceptor [6-7,17,38,59]. The approved drug propranolol is a non-selective β-adrenoceptor antagonist.
Primary Transduction Mechanisms
Transducer Effector/Response
Gs family Adenylate cyclase stimulation
Comments:  Stimulation of adenylate cyclase (AC) causes the conversion of ATP into cAMP. This activates protein kinase C, which in turn phosphorylates several substrates, for example L-type Ca2+ channels. In adipocites this leads to the phosphorylation and activation of the hormone sensitive lipase.
References:  11,31,54
Secondary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Guanylate cyclase stimulation
Comments:  β3-adrenoceptors stimulate nitric oxide production through the activation of endothelial nitric oxide synthase. Nitric oxide activates guanylate cyclase and increases cGMP levels.
References:  34,63,66
Tissue Distribution
Adipose, gall bladder > small intestine > stomach, prostate > left atrium > bladder.
Species:  Human
Technique:  RT-PCR and RNase protection assay.
References:  5,30
Brown adipose tissue.
Species:  Human
Technique:  PCR.
References:  33
Endothelium of coronary microarteries.
Species:  Human
Technique:  Immunohistochemistry.
References:  16
Adipose tissue.
Species:  Rat
Technique:  Northern blotting.
References:  23
Internal anal sphincter (IAS) smooth muscle.
Species:  Rat
Technique:  Western blotting.
References:  34
Expression Datasets

Show »

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]

There should be a chart of expression data here, you may need to enable JavaScript!
Functional Assays
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:  23
Measurement of cAMP levels in CHO cells stably transfected with the human β3 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  cAMP accumulation.
References:  18,24,38,40
Measurement of cAMP levels in mouse brown adipocytes in culture.
Species:  Mouse
Tissue:  Brown adipocytes in culture.
Response measured:  cAMP accumulation.
References:  11
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:  71
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:  71
Measurement of mechanical and electrical responses of endomyocardium when exposed to β3-adrenoceptor agonists.
Species:  Human
Tissue:  Endomyocardial biopsies obtained form the right interventricular septum.
Response measured:  Increase in peak tension.
Decrease in amplitude of the action potential and acceleration of the repolarisation phase.
References:  21
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:  9
Physiological Functions
Lipolysis (glycerol release).
Species:  Mouse
Tissue:  3T3-F442A-derived adipocytes.
References:  38
Lipolysis (glycerol release).
Species:  Rat
Tissue:  White adipocytes.
References:  22
Relaxation of rat abdominal aorta smooth muscle.
Species:  Rat
Tissue:  Abdominal aorta smooth muscle.
References:  37
Glucose uptake.
Species:  Mouse
Tissue:  Brown adipocytes in culture.
References:  11
Vasodilatation via nitric oxide and vessel hyperpolarisation.
Species:  Human
Tissue:  Coronary resistance arteries.
References:  16
All of the β-adrenoceptors cause relaxation of the internal anal sphincter (IAS).
Species:  Rat
Tissue:  Internal anal sphincter (IAS).
References:  34
Relaxation of colon and oesophagus.
Species:  Mouse
Tissue:  Colon, oesophagus.
References:  44
Lipolysis, thermogenesis.
Species:  Human
Tissue:  Brown fat.
References:  27
Lipolysis.
Species:  Human
Tissue:  White fat.
References:  35,60
Relaxation.
Species:  Human
Tissue:  Smooth muscle cells isolated from the colon.
References:  4,52
Negative inotropic effect.
Species:  Human
Tissue:  Heart.
References:  21
Relaxation.
Species:  Human
Tissue:  Myometrium.
References:  48
Decrease in gastrointestinal motility.
Species:  Mouse
Tissue:  Small intestine and stomach.
References:  20
Physiological Consequences of Altering Gene Expression
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:  61
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:  12
In β3-adrenoceptor knockout mice, activation of β1 receptors compensate for the lack of β3 receptor and cause relaxation of colon and oesophagus muscle, as in the wild-type.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  44
Cadiac overexpression of the human β3-adrenoceptor results in positive inotropy.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  29
β3-adrenoceptor knockout mice exhibit a complete loss of β3 agonist-induced AC 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:  57
Phenotypes, Alleles and Disease Models Mouse data from MGI

Show »

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
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Trp64 -> Arg polymorphism is associated with impaired insulin secretion.
References:  13
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:  14,28,43,47,55,65,70
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:  67
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Trp64 -> Arg polymorphism is associated with hypertension.
References:  62
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Trp64 -> Arg polymorphism is associated with a lower resting autonomic nervous system activity.
References:  53
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:  39
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Trp64 -> Arg polymorphism is associated with mild gestational diabetes mellitus.
References:  19
General Comments
For a review on the β-adrenoceptor polymorphisms see reference [32].

References

Show »

1. Aparici M, Gómez-Angelats M, Vilella D, Otal R, Carcasona C, Viñals M, Ramos I, Gavaldà A, De Alba J, Gras J et al.. (2012) Pharmacological characterization of abediterol, a novel inhaled β(2)-adrenoceptor agonist with long duration of action and a favorable safety profile in preclinical models. J. Pharmacol. Exp. Ther., 342 (2): 497-509. [PMID:22588259]

2. Baker JG. (2005) The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors. Br J Pharmacol, 144: 317-322. [PMID:15655528]

3. Baker JG. (2010) The selectivity of beta-adrenoceptor agonists at human beta1-, beta2- and beta3-adrenoceptors. Br. J. Pharmacol., 160 (5): 1048-61. [PMID:20590599]

4. Bardou M, Dousset B, Deneux-Tharaux C, Smadja C, Naline E, Chaput JC, Naveau S, Manara L, Croci T, Advenier C. (1998) In vitro inhibition of human colonic motility with SR 59119A and SR 59104A: evidence of a beta3-adrenoceptor-mediated effect. Eur J Pharmacol., 353: 281-287. [PMID:9726658]

5. Berkowitz DE, Nardone NA, Smiley RM, Price DT, Kreutter DK, Fremeau RT, Schwinn DA. (1995) Distribution of beta 3-adrenoceptor mRNA in human tissues. Eur J Pharmacol., 289: 223-228. [PMID:7621895]

6. Blin N, Camoin L, Maigret B, Strosberg AD. (1993) Structural and conformational features determining selective signal transduction in the beta 3-adrenergic receptor. Mol Pharmacol., 44: 1094-1104. [PMID:7903415]

7. Blin N, Nahmias C, Drumare MF, Strosberg AD. (1994) Mediation of most atypical effects by species homologues of the beta 3-adrenoceptor. Br J Pharmacol, 112: 911-919. [PMID:7921620]

8. Breit A, Lagacé M, Bouvier M. (2004) Hetero-oligomerization between beta2- and beta3-adrenergic receptors generates a beta-adrenergic signaling unit with distinct functional properties. J. Biol. Chem., 279 (27): 28756-65. [PMID:15123695]

9. Brixius K, Bloch W, Pott C, Napp A, Krahwinkel A, Ziskoven C, Koriller M, Mehlhorn U, Hescheler J, Fleischmann B, Schwinger RH. (2004) Mechanisms of beta 3-adrenoceptor-induced eNOS activation in right atrial and left ventricular human myocardium. Br J Pharmacol., 143: 1014-1022. [PMID:15466444]

10. Candelore MR, Deng L, Tota L, Guan XM, Amend A, Liu Y, Newbold R, Cascieri MA, Weber AE. (1999) Potent and selective human beta(3)-adrenergic receptor antagonists. J Pharmacol Exp Ther, 290: 649-655. [PMID:10411574]

11. Chernogubova E, Cannon B, Bengtsson T. (2004) Norepinephrine increases glucose transport in brown adipocytes via beta3-adrenoceptors through a cAMP, PKA, and PI3-kinase-dependent pathway stimulating conventional and novel PKCs. Endocrinology, 145: 269-280. [PMID:14551227]

12. Chernogubova E, Hutchinson DS, Nedergaard J, Bengtsson T. (2005) Alpha1- and beta1-adrenoceptor signaling fully compensates for beta3-adrenoceptor deficiency in brown adipocyte norepinephrine-stimulated glucose uptake. Endocrinology, 146: 2271-2284. [PMID:15665039]

13. Christiansen C, Poulsen P, Beck-Nielsen H. (1999) The Trp64Arg mutation of the adrenergic beta-3 receptor gene impairs insulin secretion: a twin study. Diabet Med, 16: 835-840. [PMID:10547210]

14. Clement K, Vaisse C, Manning BS, Basdevant A, Guy-Grand B, Ruiz J, Silver KD, Shuldiner AR, Froguel P, Strosberg AD. (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: 352-354. [PMID:7609752]

15. De Ponti F, Gibelli G, Croci T, Arcidiaco M, Crema F, Manara L. (1996) Functional evidence of atypical beta 3-adrenoceptors in the human colon using the beta 3-selective adrenoceptor antagonist, SR 59230A. Br J Pharmacol., 117: 1374-1376. [PMID:8730727]

16. Dessy C, Moniotte S, Ghisdal P, Havaux X, Noirhomme P, Balligand JL. (2004) Endothelial beta3-adrenoceptors mediate vasorelaxation of human coronary microarteries through nitric oxide and endothelium-dependent hyperpolarization. Circulation, 110: 948-954. [PMID:15302798]

17. Dolan JA, Muenkel HA, Burns MG, Pellegrino SM, Fraser CM, Pietri F, Strosberg AD, Largis EE, Dutia MD, Bloom JD, et al.. (1994) Beta-3 adrenoceptor selectivity of the dioxolane dicarboxylate phenethanolamines. J Pharmacol Exp Ther., 269: 1000-1006. [PMID:7912272]

18. Emorine LJ, Marullo S, Briend-Sutren MM, Patey G, Tate K, Delavier-Klutchko C, Strosberg AD. (1989) Molecular characterization of the human β3-adrenergic receptor. Science, 245: 1118-1121. [PMID:2570461]

19. Festa A, Krugluger W, Shnawa N, Hopmeier P, Haffner SM, Schernthaner G. (1999) Trp64Arg polymorphism of the beta3-adrenergic receptor gene in pregnancy: association with mild gestational diabetes mellitus. J Clin Endocrinol Metab., 84: 1695-1699. [PMID:10323402]

20. Fletcher DS, Candelore MR, Grujic D, Lowell BB, Luell S, Susulic VS, MacIntyre DE. (1998) Beta-3 adrenergic receptor agonists cause an increase in gastrointestinal transit time in wild-type mice, but not in mice lacking the beta-3 adrenergic receptor. J Pharmacol Exp Ther., 287: 720-724. [PMID:9808702]

21. Gauthier C, Tavernier G, Charpentier F, Langin D, Le Marec H. (1996) Functional beta3-adrenoceptor in the human heart. J Clin Invest., 98: 556-562. [PMID:8755668]

22. Germack R, Starzec AB, Vassy R, Perret GY. (1997) Beta-adrenoceptor subtype expression and function in rat white adipocytes. Br J Pharmacol., 120: 201-210. [PMID:9117110]

23. Granneman JG, Lahners KN, Chaudhry A. (1991) Molecular cloning and expression of the rat beta 3-adrenergic receptor. Mol Pharmacol., 40: 895-899. [PMID:1684635]

24. Hoffmann C, Leitz MR, Oberdorf-Maass S, Lohse MJ, Klotz KN. (2004) Comparative pharmacology of human beta-adrenergic receptor subtypes - characterization of stably transfected receptors in CHO cells. Naunyn Schmiedebergs Arch Pharmacol., 369: 151-159. [PMID:14730417]

25. Hutchinson DS, Bengtsson T, Evans BA, Summers RJ. (2002) Mouse beta 3a- and beta 3b-adrenoceptors expressed in Chinese hamster ovary cells display identical pharmacology but utilize distinct signalling pathways. Br. J. Pharmacol., 135 (8): 1903-14. [PMID:11959793]

26. Hutchinson DS, Chernogubova E, Sato M, Summers RJ, Bengtsson T. (2006) Agonist effects of zinterol at the mouse and human beta(3)-adrenoceptor. Naunyn Schmiedebergs Arch. Pharmacol., 373 (2): 158-68. [PMID:16601951]

27. Jockers R, Issad T, Zilberfarb V, de Coppet P, Marullo S, Strosberg AD. (1998) Desensitization of the beta-adrenergic response in human brown adipocytes. Endocrinology., 139: 2676-2684. [PMID:9607772]

28. Kimura K, Sasaki N, Asano A, Mizukami J, Kayahashi S, Kawada T, Fushiki T, Morimatsu M, Yoshida T, Saito M. (2000) Mutated human beta3-adrenergic receptor (Trp64Arg) lowers the response to beta3-adrenergic agonists in transfected 3T3-L1 preadipocytes. Horm Metab Res., 32: 91-96. [PMID:10786926]

29. Kohout TA, Takaoka H, McDonald PH, Perry SJ, Mao L, Lefkowitz RJ, Rockman HA. (2001) Augmentation of cardiac contractility mediated by the human beta(3)-adrenergic receptor overexpressed in the hearts of transgenic mice. Circulation., 104: 2485-2491. [PMID:11705829]

30. Krief S, Lonnqvist F, Raimbault S, Baude B, Van Spronsen A, Arner P, Strosberg AD, Ricquier D, Emorine LJ. (1993) Tissue distribution of beta 3-adrenergic receptor mRNA in man. J Clin Invest., 91: 344-349. [PMID:8380813]

31. Large V, Arner P, Reynisdottir S, Grober J, Van Harmelen V, Holm C, Langin D. (1998) Hormone-sensitive lipase expression and activity in relation to lipolysis in human fat cells. J Lipid Res., 39: 1688-1695. [PMID:9717730]

32. Leineweber K, Buscher R, Bruck H, Brodde OE. (2004) Beta-adrenoceptor polymorphisms. Naunyn Schmiedebergs Arch Pharmacol, 369: 1-22. [PMID:14647973]

33. Lelias JM, Kaghad M, Rodriguez M, Chalon P, Bonnin J, Dupre I, Delpech B, Bensaid M, LeFur G, Ferrara P, Caput D. (1993) Molecular cloning of a human beta 3-adrenergic receptor cDNA. FEBS Lett., 324: 127-130. [PMID:8389717]

34. Li F, De Godoy M, Rattan S. (2004) Role of adenylate and guanylate cyclases in beta1-, beta2-, and beta3-adrenoceptor-mediated relaxation of internal anal sphincter smooth muscle. J Pharmacol Exp Ther, 308: 1111-1120. [PMID:14711933]

35. Lonnqvist F, Krief S, Strosberg AD, Nyberg S, Emorine LJ, Arner P. (1993) Evidence for a functional beta 3-adrenoceptor in man. Br J Pharmacol., 110: 929-936. [PMID:7905344]

36. Louis SN, Nero TL, Iakovidis D, Jackman GP, Louis WJ. (1999) LK 204-545, a highly selective beta1-adrenoceptor antagonist at human beta-adrenoceptors. Eur J Pharmacol, 367: 431-435. [PMID:10079020]

37. Matsushita M, Horinouchi T, Tanaka Y, Tsuru H, Koike K. (2003) Characterization of beta 3-adrenoceptor-mediated relaxation in rat abdominal aorta smooth muscle. Eur J Pharmacol, 482: 235-244. [PMID:14660028]

38. Mejean A, Guillaume JL, Strosberg AD. (1995) Carazolol: a potent, selective beta 3-adrenoceptor agonist. Eur J Pharmacol., 291: 359-366. [PMID:8719421]

39. Melis MG, Secchi G, Brizzi P, Severino C, Maioli M, Tonolo G. (2002) The Trp64Arg beta3-adrenergic receptor amino acid variant confers increased sensitivity to the pressor effects of noradrenaline in Sardinian subjects. Clin Sci (Lond), 103: 397-402. [PMID:12241539]

40. Molenaar P, Sarsero D, Arch JR, Kelly J, Henson SM, Kaumann AJ. (1997) Effects of (-)-RO363 at human atrial beta-adrenoceptor subtypes, the human cloned beta 3-adrenoceptor and rodent intestinal beta 3-adrenoceptors. Br J Pharmacol, 120: 165-176. [PMID:9117106]

41. Muzzin P, Revelli JP, Kuhne F, Gocayne JD, McCombie WR, Venter JC, Giacobino JP, Fraser CM. (1991) An adipose tissue-specific beta-adrenergic receptor. Molecular cloning and down-regulation in obesity. J Biol Chem., 266: 24053-24058. [PMID:1721063]

42. Nahmias C, Blin N, Elalouf JM, Mattei MG, Strosberg AD, Emorine LJ. (1991) Molecular characterization of the mouse beta 3-adrenergic receptor: relationship with the atypical receptor of adipocytes. EMBO J., 10: 3721-3727. [PMID:1718744]

43. Ochoa MC, Marti A, Azcona C, Chueca M, Oyarzábal M, Pelach R, Patiño A, Moreno-Aliaga MJ, Martínez-González MA, Martínez JA, Groupo de Estudio Navarro de Obesidad Infantil (GENOI). (2004) Gene-gene interaction between PPAR gamma 2 and ADR beta 3 increases obesity risk in children and adolescents. Int. J. Obes. Relat. Metab. Disord., 28 Suppl 3: S37-41. [PMID:15543217]

44. Oostendorp J, Preitner F, Moffatt J, Jimenez M, Giacobino JP, Molenaar P, Kaumann AJ. (2000) Contribution of beta-adrenoceptor subtypes to relaxation of colon and oesophagus and pacemaker activity of ureter in wildtype and beta(3)-adrenoceptor knockout mice. Br J Pharmacol, 130: 747-758. [PMID:10864880]

45. Pietri-Rouxel F, Lenzen G, Kapoor A, Drumare MF, Archimbault P, Strosberg AD, Manning BS. (1995) Molecular cloning and pharmacological characterization of the bovine beta 3-adrenergic receptor. Eur J Biochem., 230: 350-358. [PMID:7601122]

46. Popp BD, Hutchinson DS, Evans BA, Summers RJ. (2004) Stereoselectivity for interactions of agonists and antagonists at mouse, rat and human beta3-adrenoceptors. Eur J Pharmacol., 484: 323-331. [PMID:14744619]

47. Ramis JM, Gonzalez-Sanchez JL, Proenza AM, Martinez-Larrad MT, Fernandez-Perez C, Palou A, Serrano-Rios M. (2004) The Arg64 allele of the beta 3-adrenoceptor gene but not the -3826G allele of the uncoupling protein 1 gene is associated with increased leptin levels in the Spanish population. Metabolism., 53: 1411-1416. [PMID:15536594]

48. Rouget C, Bardou M, Breuiller-FouchÃ? M, Loustalot C, Qi H, Naline E, Croci T, Cabrol D, Advenier C, Leroy MJ. (2005) beta3-adrenoceptor is the predominant beta-adrenoceptor subtype in human myometrium and its Expression is up-regulated in pregnancy. J Clin Endocrinol Metab., 90: 1644-1650. [PMID:15585565]

49. Sato M, Horinouchi T, Hutchinson DS, Evans BA, Summers RJ. (2007) Ligand-directed signaling at the beta3-adrenoceptor produced by 3-(2-Ethylphenoxy)-1-[(1,S)-1,2,3,4-tetrahydronapth-1-ylamino]-2S-2-propanol oxalate (SR59230A) relative to receptor agonists. Mol. Pharmacol., 72 (5): 1359-68. [PMID:17717109]

50. Sato M, Hutchinson DS, Halls ML, Furness SG, Bengtsson T, Evans BA, Summers RJ. (2012) Interaction with caveolin-1 modulates G protein coupling of mouse β3-adrenoceptor. J. Biol. Chem., 287 (24): 20674-88. [PMID:22535965]

51. Sato Y, Kurose H, Isogaya M, Nagao T. (1996) Molecular characterization of pharmacological properties of T-0509 for beta-adrenoceptors. Eur J Pharmacol., 315: 363-367. [PMID:8982677]

52. Severi C, Tattoli I, Romano G, Corleto VD, Delle Fave G. (2004) Beta3-adrenoceptors: relaxant function and mRNA detection in smooth muscle cells isolated from the human colon. Can J Physiol Pharmacol., 82: 515-522. [PMID:15389299]

53. Shihara N, Yasuda K, Moritani T, Ue H, Adachi T, Tanaka H, Tsuda K, Seino Y. (1999) The association between Trp64Arg polymorphism of the beta3-adrenergic receptor and autonomic nervous system activity. J Clin Endocrinol Metab, 84: 1623-1627. [PMID:10323390]

54. Skeberdis VA, Jurevicius J, Fischmeister R. (1999) b3-adrenergic regulation of cardiac L-type Ca2+ current in human atrial myocytes. Biophys J., 76: A343-A343.

55. Snitker S, Odeleye OE, Hellmer J, Boschmann M, Monroe MB, Shuldiner AR, Ravussin E. (1997) No effect of the Trp64Arg beta 3-adrenoceptor variant on in vivo lipolysis in subcutaneous adipose tissue. Diabetologia, 40: 838-842. [PMID:9243106]

56. Strosberg AD. (1997) Structure and function of the beta 3-adrenergic receptor. Annu Rev Pharmacol Toxicol., 37: 421-450. [PMID:9131260]

57. Susulic VS, Frederich RC, Lawitts J, Tozzo E, Kahn BB, Harper ME, Himms-Hagen J, Flier JS, Lowell BB. (1995) Targeted disruption of the beta 3-adrenergic receptor gene. J Biol Chem, 270: 29483-29492. [PMID:7493988]

58. Takasu T, Ukai M, Sato S, Matsui T, Nagase I, Maruyama T, Sasamata M, Miyata K, Uchida H, Yamaguchi O. (2007) Effect of (R)-2-(2-aminothiazol-4-yl)-4'-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function. J. Pharmacol. Exp. Ther., 321 (2): 642-7. [PMID:17293563]

59. Tate KM, Briend-Sutren MM, Emorine LJ, Delavier-Klutchko C, Marullo S, Strosberg AD. (1991) Expression of three human beta-adrenergic-receptor subtypes in transfected Chinese hamster ovary cells. Eur J Biochem, 196: 357-361. [PMID:1848818]

60. Tavernier G, Barbe P, Galitzky J, Berlan M, Caput D, Lafontan M, Langin D. (1996) Expression of beta3-adrenoceptors with low lipolytic action in human subcutaneous white adipocytes. J Lipid Res., 37: 87-97. [PMID:8820105]

61. Tavernier G, Toumaniantz G, Erfanian M, Heymann MF, Laurent K, Langin D, Gauthier C. (2003) beta3-Adrenergic stimulation produces a decrease of cardiac contractility ex vivo in mice overexpressing the human beta3-adrenergic receptor. Cardiovasc Res., 59: 288-296. [PMID:12909312]

62. Tonolo G, Melis MG, Secchi G, Atzeni MM, Angius MF, Carboni A, Ciccarese M, Malavasi A, Maioli M. (1999) Association of Trp64Arg beta 3-adrenergic-receptor gene polymorphism with essential hypertension in the Sardinian population. J Hypertens., 17: 33-38. [PMID:10100091]

63. Trochu JN, Leblais V, Rautureau Y, Beverelli F, Le Marec H, Berdeaux A, Gauthier C. (1999) Beta 3-adrenoceptor stimulation induces vasorelaxation mediated essentially by endothelium-derived nitric oxide in rat thoracic aorta. Br J Pharmacol., 128: 69-76. [PMID:10498836]

64. Uehling DE, Shearer BG, Donaldson KH, Chao EY, Deaton DN, Adkison KK, Brown KK, Cariello NF, Faison WL, Lancaster ME et al.. (2006) Biarylaniline phenethanolamines as potent and selective beta3 adrenergic receptor agonists. J. Med. Chem., 49 (9): 2758-71. [PMID:16640337]

65. Umekawa T, Yoshida T, Sakane N, Kogure A, Kondo M, Honjyo H. (1999) Trp64Arg mutation of beta3-adrenoceptor gene deteriorates lipolysis induced by beta3-adrenoceptor agonist in human omental adipocytes. Diabetes., 48: 117-120. [PMID:9892231]

66. Varghese P, Harrison RW, Lofthouse RA, Georgakopoulos D, Berkowitz DE, Hare JM. (2000) Beta(3)-adrenoceptor deficiency blocks nitric oxide-dependent inhibition of myocardial contractility. J Clin Invest., 106: 697-703. [PMID:10974023]

67. Walston J, Silver K, Bogardus C, Knowler WC, Celi FS, Austin S, Manning B, Strosberg AD, Stern MP, Raben N, et al.. (1995) Time of onset of non-insulin-dependent diabetes mellitus and genetic variation in the beta 3-adrenergic-receptor gene. N Engl J Med., 333: 343-347. [PMID:7609750]

68. Weber AE, Ok HO, Alvaro RF, Candelore MR, Cascieri MA, Chiu SH, Deng L, Forrest MJ, Hom GJ, Hutchins JE et al.. (1998) 3-Pyridyloxypropanolamine agonists of the beta 3 adrenergic receptor with improved pharmacokinetic properties. Bioorg. Med. Chem. Lett., 8 (16): 2111-6. [PMID:9873496]

69. Yanagisawa T, Sato T, Yamada H, Sukegawa J, Nunoki K. (2000) Selectivity and potency of agonists for the three subtypes of cloned human beta-adrenoceptors expressed in Chinese hamster ovary cells. Tohoku J. Exp. Med., 192 (3): 181-93. [PMID:11249148]

70. Zhang Y, Wat N, Stratton IM, Warren-Perry MG, Orho M, Groop L, Turner RC. (1996) UKPDS 19: heterogeneity in NIDDM: separate contributions of IRS-1 and beta 3-adrenergic-receptor mutations to insulin resistance and obesity respectively with no evidence for glycogen synthase gene mutations. UK Prospective Diabetes Study. Diabetologia., 39: 1505-1511. [PMID:8960833]

71. Zilberfarb V, Pietri-Rouxel F, Jockers R, Krief S, Delouis C, Issad T, Strosberg AD. (1997) Human immortalized brown adipocytes express functional beta3-adrenoceptor coupled to lipolysis. J Cell Sci., 110: 801-807. [PMID:9133667]

Contributors

Show »

How to cite this page

Richard A. Bond, David B. Bylund, Douglas C. Eikenburg, J. Paul Hieble, Rebecca Hills, Kenneth P. Minneman, Sergio Parra.
Adrenoceptors: β3-adrenoceptor. Last modified on 13/07/2018. Accessed on 15/11/2018. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=30.