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β2-adrenoceptor

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Immunopharmacology Ligand target has curated data in GtoImmuPdb

Target id: 29

Nomenclature: β2-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 7 413 5q32 ADRB2 adrenoceptor beta 2 51
Mouse 7 418 18 35.1 cM Adrb2 adrenergic receptor, beta 2 3
Rat 7 418 18q12.1 Adrb2 adrenoceptor beta 2 34
Previous and Unofficial Names Click here for help
ADRB2R | ADRBR | B2AR | beta-2 adrenergic receptor | beta-2 adrenoreceptor | Adrb-2 | beta 2-AR | Gpcr7 | adrenoceptor beta 2, surface | adrenergic receptor
Database Links Click here for help
Specialist databases
GPCRdb adrb2_human (Hs), adrb2_mouse (Mm), adrb2_rat (Rn)
Other databases
Alphafold P07550 (Hs), P18762 (Mm), P10608 (Rn)
ChEMBL Target CHEMBL210 (Hs), CHEMBL3707 (Mm), CHEMBL3754 (Rn)
DrugBank Target P07550 (Hs)
Ensembl Gene ENSG00000169252 (Hs), ENSMUSG00000045730 (Mm), ENSRNOG00000019217 (Rn)
Entrez Gene 154 (Hs), 11555 (Mm), 24176 (Rn)
Human Protein Atlas ENSG00000169252 (Hs)
KEGG Gene hsa:154 (Hs), mmu:11555 (Mm), rno:24176 (Rn)
OMIM 109690 (Hs)
Pharos P07550 (Hs)
RefSeq Nucleotide NM_000024 (Hs), NM_007420 (Mm), NM_012492 (Rn)
RefSeq Protein NP_000015 (Hs), NP_031446 (Mm), NP_036624 (Rn)
SynPHARM 1862 (in complex with (-)-adrenaline)
1879 (in complex with alprenolol)
80268 (in complex with carazolol)
1873 (in complex with ICI 118551)
1888 (in complex with timolol)
UniProtKB P07550 (Hs), P18762 (Mm), P10608 (Rn)
Wikipedia ADRB2 (Hs)
Selected 3D Structures Click here for help
Image of receptor 3D structure from RCSB PDB
Description:  Irreversible Agonist-β2-Adrenoceptor Complex
PDB Id:  3PDS
Resolution:  3.5Å
Species:  Human
References:  76
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human β2-adrenergic receptor in complex with the inverse agonist ICI 118,551
PDB Id:  3NY8
Ligand:  ICI 118551
Resolution:  2.84Å
Species:  Human
References:  92
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the β2 adrenergic receptor-Gs protein complex
PDB Id:  3SN6
Resolution:  3.2Å
Species:  None
References:  74
Image of receptor 3D structure from RCSB PDB
Description:  Cholesterol bound form of human β2-adrenergic receptor
PDB Id:  3D4S
Ligand:  cholesterol
Resolution:  2.8Å
Species:  Human
References:  37
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human β2-adrenergic receptor in complex with the neutral antagonist alprenolol
PDB Id:  3NYA
Ligand:  alprenolol
Resolution:  3.16Å
Species:  Human
References:  92
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human β2-adrenoceptor
PDB Id:  2R4S
Resolution:  3.4Å
Species:  Human
References:  73
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of a methylated β2-Adrenergic Receptor-Fab complex
PDB Id:  3KJ6
Resolution:  3.4Å
Species:  Human
References:  19
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the human β2-adrenoceptor
PDB Id:  2R4R
Resolution:  3.4Å
Species:  Human
References:  73
Image of receptor 3D structure from RCSB PDB
Description:  High resolution crystal structure of human β2-adrenergic G protein-coupled receptor. N.B. the representation of carazolol on PBD shows the S isomer, which our ligand entry specifies the racemate.
PDB Id:  2RH1
Ligand:  carazolol
Resolution:  2.4Å
Species:  Human
References:  26
Associated Proteins Click here for help
Interacting Proteins
Name Effect References
β2-adrenoceptor 5,21,38,53,68
β1-adrenoceptor 56-57,68,97
β3-adrenoceptor 21
α1D-adrenoceptor 90
α2A-adrenoceptor 53
5-HT4 receptor 18
δ receptor 49,67
κ receptor 49
μ receptor 53
EP1 receptor 66
B2 receptor 35
AT1 receptor 15
CXCR4 55
CB1 receptor 44,53
mouse 71 (M71) Olfactory receptor 36
D1 receptor 53
OT receptor 94-95
epidermal growth factor receptor 64
GluA1 48
Natural/Endogenous Ligands Click here for help
(-)-adrenaline
noradrenaline
(-)-noradrenaline
Zn2+
Comments: Adrenaline exhibits greater potency than noradrenaline
Potency order of endogenous ligands (Human)
(-)-adrenaline > (-)-noradrenaline

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
CHF-6366 Small molecule or natural product Click here for species-specific activity table Hs Agonist 11.4 pKd 25
⤷ pKd 11.4 (Kd 4x10-12 M) [25]
Description: Binding to human cloned β2 receptor using 125I-cyanopindolol as tracer
[3H]CGP12177 Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Partial agonist 9.8 pKd 12
⤷ pKd 9.8 (Kd 1.44x10-10 M) [12]
Description: Binding to human &beta2-adrenoceptor expressed in CHO-K1 cells, in a whole cell binding assay.
orciprenaline Small molecule or natural product Approved drug Primary target of this compound Hs Agonist 5.3 pKd 82
⤷ pKd 5.3 (Kd 4.81x10-6 M) [82]
pindolol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Partial agonist 9.4 pKi 52
⤷ pKi 9.4 (Ki 4x10-10 M) [52]
arformoterol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Ligand has a PDB structure Immunopharmacology Ligand Hs Agonist 8.6 pKi 2
⤷ pKi 8.6 (Ki 2.6x10-9 M) [2]
indacaterol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Agonist 7.8 pKi 16-17
⤷ pKi 7.8 (Ki 1.59x10-8 M) [16-17]
fenoterol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 6.9 pKi 7,14,29
⤷ pKi 6.9 (Ki 1.26x10-7 M) [7,14,29]
ractopamine Small molecule or natural product Hs Agonist 6.7 pKi 29,50
⤷ pKi 6.7 (Ki 1.8x10-7 M) [29,50]
Description: Inhibitory constant determined from a standard radioligand displacement assay using human β2-adrenoceptors expressed in Sf-9 cells and [3H]CGP1217 as tracer.
isoprenaline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Full agonist 6.4 pKi 78
⤷ pKi 6.4 [78]
(-)-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 6.0 – 6.2 pKi 32,42,47
⤷ pKi 6.0 – 6.2 [32,42,47]
salbutamol Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Partial agonist 5.8 – 6.1 pKi 10,45
⤷ pKi 5.8 – 6.1 (Ki 1.58x10-6 – 7.94x10-7 M) [10,45]
ephedrine Small molecule or natural product Approved drug Primary target of this compound Hs Partial agonist 5.6 pKi 47
⤷ pKi 5.6 [47]
terbutaline Small molecule or natural product Approved drug Primary target of this compound Hs Partial agonist 5.6 pKi 10
⤷ pKi 5.6 (Ki 2.51x10-6 M) [10]
noradrenaline Small molecule or natural product Click here for species-specific activity table Ligand is endogenous in the given species Hs Full agonist 5.4 pKi 60
⤷ pKi 5.4 [60]
levosalbutamol Small molecule or natural product Approved drug Ligand has a PDB structure Immunopharmacology Ligand Hs Partial agonist 5.3 pKi 81
⤷ pKi 5.3 (Ki 5.623x10-6 M) [81]
Description: Measuring displacement of [3H]-DHA from recombinant human β2 adrenoceptors expressed in HEK293T cells.
(-)-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 Agonist 4.6 – 4.8 pKi 32,42
⤷ pKi 4.6 – 4.8 [32,42]
formoterol Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Agonist 10.1 pEC50 11
⤷ pEC50 10.1 [11]
BI-167107 Small molecule or natural product Click here for species-specific activity table Hs Agonist 10.0 pEC50 41
⤷ pEC50 10.0 (EC50 1x10-10 M) [41]
Description: Determined in an intracellular cAMP accumulation assay in CHO-K1 cells expressing hβ2-AR
salmeterol Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Full agonist 9.9 pEC50 11
⤷ pEC50 9.9 (EC50 1.2x10-10 M) [11]
zinterol Small molecule or natural product Hs Agonist 9.5 pEC50 11
⤷ pEC50 9.5 [11]
vilanterol Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Agonist 9.4 pEC50 71
⤷ pEC50 9.4 (EC50 3.98x10-10 M) [71]
procaterol Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Agonist 8.4 pEC50 11
⤷ pEC50 8.4 [11]
solabegron Small molecule or natural product Click here for species-specific activity table Hs Agonist 5.9 pEC50 91
⤷ pEC50 5.9 [91]
mirabegron Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist <5.0 pEC50 86
⤷ pEC50 <5.0 (EC50 >1x10-5 M) [86]
olodaterol Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Agonist 10.0 pIC50 20
⤷ pIC50 10.0 (IC50 1x10-10 M) [20]
abediterol Small molecule or natural product Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Full agonist 9.2 pIC50 6
⤷ pIC50 9.2 (IC50 6x10-10 M) [6]
Description: Membrane radioligand displacement assay using [3H]CGP12177 as tracer.
clenbuterol Small molecule or natural product Hs Agonist 6.2 pIC50 11,14,50
⤷ pIC50 6.2 (IC50 5.7x10-7 M) [11,14,50]
cimaterol Small molecule or natural product Click here for species-specific activity table Hs Agonist - - 11
⤷ [11]
Agonist Comments
The drug ephedrine is an adrenoceptor agonist and likely has activity across several family members. We have tagged the β2-adrenoceptor as the drug's primary target, as this is the only human data discovered to date.
Although the results tables presented in [81] state that salbutamol was tested, their Materials and Methods section indicates that in fact these experiments tested R-(-)salbutamol which is a synonym for levosalbutamol.
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
butoxamine Small molecule or natural product Rn Antagonist 6.4 pKB 40
⤷ pKB 6.4 (KB 3.55x10-7 M) [40]
[125I]ICYP Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 11.1 pKd 63,78
⤷ pKd 11.1 (Kd 7.9x10-12 M) It is necessary to use an excess of a β1-adrenoceptor-selective ligand such as CGP20712A in combination with this radioligand in order to allow visualisation of β2-adrenoceptor binding in native tissues. [63,78]
carazolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.9 pKi 77
⤷ pKi 9.9 (Ki 1.14x10-10 M) [77]
timolol Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Hs Antagonist 9.7 pKi 10
⤷ pKi 9.7 [10]
carvedilol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.4 – 9.9 pKi 10,24
⤷ pKi 9.4 – 9.9 [10,24]
CGP 12177 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.4 pKi 10,63
⤷ pKi 9.4 [10,63]
ICI 118551 Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inverse agonist 9.2 – 9.5 pKi 10,13,63
⤷ pKi 9.2 – 9.5 [10,13,63]
propranolol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.1 – 9.5 pKi 10,13,45,63
⤷ pKi 9.1 – 9.5 [10,13,45,63]
levobunolol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.3 pKi 8
⤷ pKi 9.3 (Ki 5.5x10-10 M) [8]
alprenolol Small molecule or natural product Approved drug Primary target of this compound Hs Partial agonist 9.0 pKi 10
⤷ pKi 9.0 [10]
SR59230A Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.5 – 9.3 pKi 10,24
⤷ pKi 8.5 – 9.3 [10,24]
bupranolol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.3 – 9.1 pKi 10,24,63
⤷ pKi 8.3 – 9.1 [10,24,63]
labetalol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Partial agonist 8.0 pKi 8
⤷ pKi 8.0 (Ki 1.1x10-8 M) [8]
nebivolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 8.0 pKi 31
⤷ pKi 8.0 [31]
Description: Radioligand binding
nadolol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 7.0 – 8.6 pKi 10,24
⤷ pKi 7.0 – 8.6 [10,24]
NIP Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.5 pKi 63
⤷ pKi 7.5 [63]
levobetaxolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.5 pKi 80
⤷ pKi 7.5 (Ki 3.26x10-8 M) [80]
propafenone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.4 pKi 8
⤷ pKi 7.4 (Ki 3.6x10-8 M) [8]
betaxolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.2 pKi 63
⤷ pKi 7.2 [63]
butoxamine Small molecule or natural product Rn Antagonist 6.3 – 6.5 pKi 22,87
⤷ pKi 6.3 – 6.5 (Ki 4.68x10-7 – 3.09x10-7 M) [22,87]
sotalol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.3 – 6.5 pKi 8,10
⤷ pKi 6.3 – 6.5 [8,10]
metoprolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.3 pKi 63
⤷ pKi 6.3 [63]
cicloprolol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pKi 63
⤷ pKi 6.2 [63]
NIHP Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.0 pKi 63
⤷ pKi 6.0 [63]
atenolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 5.6 – 6.0 pKi 10,63
⤷ pKi 5.6 – 6.0 [10,63]
LK 204-545 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.2 pKi 63
⤷ pKi 5.2 [63]
View species-specific antagonist tables
Antagonist Comments
The approved drug propranolol is a non-selective β-adrenoceptor antagonist.
Propafenone may also act to block α-subunits of sodium ion channels (see the Voltage-gated sodium channels family in the Ion Channels section of this website for further details).
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
Zn2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Positive 5.3 pKi 84-85
⤷ pKi 5.3 [84-85]
Zn2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Negative 3.3 pKi 84-85
⤷ pKi 3.3 [84-85]
AS408 Small molecule or natural product Ligand has a PDB structure N/A - - - 61
⤷ [61]
View species-specific allosteric modulator tables
Allosteric Modulator Comments
Zn2+ appears to have both positive and negative effects on agonist affinity. At low concentrations it appears to enhance agonist affinity and agonist-stimulated cAMP accumulation. At high concentrations Zn2+ inhibits agonist binding but slows antagonist dissociation [84-85].
Immunopharmacology Comments
β2-ARs are expressed on innate and adaptive immune cells of humans and rodents, and are reported to have an immuno-modulating effect [30].
Cell Type Associations
Immuno Cell Type:  B cells
Cell Ontology Term:   B cell (CL:0000236)
Comment:  B cells from patients with rheumatoid arthritis express lower levels of β2-ARs compared with healthy subjects.
References:  9
Immuno Cell Type:  T cells
Cell Ontology Term:   CD8-positive, alpha-beta T cell (CL:0000625)
Comment:  CD8+ T cells from patients with rheumatoid arthritis express lower levels of β2-ARs compared with healthy subjects.
References:  9
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   monocyte (CL:0000576)
Comment:  Monocytes from patients with rheumatoid arthritis express lower levels of β2-ARs compared with healthy subjects.
References:  9
Immuno Process Associations
Immuno Process:  Antigen presentation
GO Annotations:  Associated to 1 GO processes
GO:0006898 receptor-mediated endocytosis IDA
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family Adenylyl cyclase stimulation
Comments:  Stimulation of adenylate cyclase (AC) causes the conversion of ATP into cAMP. This activates protein kinase A, which in turn phosphorylates several substrates, for example L-type Ca2+ channels.
References:  59,79,83,93
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Guanylate cyclase stimulation
Comments:  Stimulation of guanylate cyclase (GC) causes an increase in cGMP levels, and subsequent activation of protein kinase G.
References:  59
Tissue Distribution Click here for help
Lung >> skeletal muscle > spleen > kidney > heart > brain > liver.
Species:  Mouse
Technique:  in situ hybridisation.
References:  4
Lung >> spleen > kidney > heart > brain > skeletal muscle > liver.
Species:  Mouse
Technique:  Radioligand binding.
References:  4
Lung > heart.
Species:  Rat
Technique:  Radioligand binding.
References:  69
Brain: Caudate, cortex, cerebellum, hippocampus, diencephalon.
Species:  Rat
Technique:  Radioligand binding.
References:  69
Internal anal sphincter (IAS) smooth muscle.
Species:  Rat
Technique:  Western blotting.
References:  59
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 rat heart and lung tissue.
Species:  Rat
Tissue:  Heart and lung.
Response measured:  cAMP accumulation.
References:  69
Measurement of cAMP levels in CHO-K1 cells expressing the human β2 receptor.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  cAMP accumulation.
References:  78
Measurement of cAMP levels in human lung epithelial cell lines.
Species:  Human
Tissue:  Calu-3 and 16HBE14o- cell lines.
Response measured:  cAMP accumulation.
References:  1
Measurement of cAMP levels in a human macrophage cell line.
Species:  Human
Tissue:  U937 cells.
Response measured:  cAMP accumulation.
References:  46
Measurement of LPS-induced cytokine release (TNFα and Il-10) from human U937 macrophage cells when treated with a β2-adrenoceptor agoinist.
Species:  Human
Tissue:  U937 cells.
Response measured:  Inhibition of TNFα release, stimulation of Il-10 release.
References:  46
Measurement of cAMP levels in Sf9 insect cells transfected with the human β2-adrenoceptor.
Species:  Human
Tissue:  Sf9 cells.
Response measured:  cAMP accumulation.
References:  79
The trachea of an anesthetized mouse is intubated and airway resistance is measured in response to intravenously injected agonists.
Species:  Mouse
Tissue:  Lung.
Response measured:  Decrease in airway resistance.
References:  23
Measurement of cAMP and Ca2+ levels in CHW fibroblast cells endogenously expressing Gs, AC and PKA and transfected with both the β2-adrenoceptor and the L-type Ca2+ channel.
Species:  Human
Tissue:  CHW-1102 fibroblast cells.
Response measured:  PTX-insensitive cAMP and Ca2+ accumulation.
References:  96
Physiological Functions Click here for help
All the β-adrenoceptors mediate relaxation of the internal anal sphincter (IAS) smooth muscle, the β2 subtype achieving this via both the Gs/cAMP pathway and the Gi/o/cGMP pathway.
Species:  Rat
Tissue:  Internal anal sphincter (IAS) smooth muscle.
References:  59
Inhibition of apoptosis via a PTX-sensitive G-protein.
Apoptosis via Gs and adenylyl cyclase.
Species:  Rat
Tissue:  Ventricular cardiomyocytes.
References:  72
Hypotension, lowering of blood pressure.
Species:  Mouse
Tissue:  Blood vessels.
References:  27
Presynaptic facilitation of noradrenlaine release from sympathetic nerves.
Species:  Rat
Tissue:  Isolated perfused kidney.
References:  54
Bronchodilation.
Species:  Mouse
Tissue:  Lung.
References:  23
Stimulation of aqueous humor formation and outflow.
Species:  Human
Tissue:  Eye.
References:  70
Uterine relaxation.
Species:  Human
Tissue:  Myometrial muscle.
References:  62
Physiological Consequences of Altering Gene Expression Click here for help
Studies involving mice overexpressing the β2-adrenoceptor show alterations in heart beat and contractile response.
Species:  Human
Tissue: 
Technique:  Transgenesis.
References:  39
Studies involving β2-adrenoceptor knockouts have only shown obvious physiological changes when under cardiovascular stress conditions. This subtype is thought not to be involved in postnatal development but does mediate peripheral vascular resistance and energy metabolism.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  27
Transgenic (TG) mice overexpressing the β2-adrenoceptor in airway smooth muscle exhibit enhanced β2 signalling and an increase in basal cAMP levels. Tracheal rings from the TG mice showed increased relaxation to a β-agonist, and in vivo studies showed resistance to methacholine-induced bronchoconstriction.
Overall, a decrease in bronchial hyperresponsiveness was seen in the TG mice: an anti-asthmatic state.
Species:  Mouse
Tissue: 
Technique:  Transgenesis.
References:  65
β1- and β2-adrenoceptor double knockout mice appear to have unaltered basal heart rate, blood pressure and metabolic rate. Stimulation of these receptors by agonists or exercise reveals they exhibit a normal exercise capacity but at a submaximal heart rate.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  75
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 
Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ		 MGI:87938  MP:0004945 abnormal bone resorption PMID: 15724149 
Adrb2+|Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2+
involves: 129S1/Sv * 129X1/SvJ		 MGI:87938  MP:0004945 abnormal bone resorption PMID: 15724149 
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 
Adrb1tm1Bkk|Adrb2tm1Bkk Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MP:0001544 abnormal cardiovascular system physiology PMID: 10358009 
Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2tm1Bkk
FVB.129-Adrb2		 MGI:87938  MP:0006319 abnormal epididymal fat pad morphology PMID: 10358008 
Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2tm1Bkk
FVB.129-Adrb2		 MGI:87938  MP:0002332 abnormal exercise endurance PMID: 10358008 
Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2tm1Bkk
FVB.129-Adrb2		 MGI:87938  MP:0001629 abnormal heart rate PMID: 10358008 
Adrb2tm1Kry|Tg(Col1a1-cre)1Kry Adrb2tm1Kry/Adrb2tm1Kry,Tg(Col1a1-cre)1Kry/0
involves: FVB		 MGI:3041865  MGI:87938  MP:0003564 abnormal insulin secretion PMID: 19103808 
Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ		 MGI:87938  MP:0005006 abnormal osteoblast physiology PMID: 15724149 
Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ		 MGI:87938  MP:0008396 abnormal osteoclast differentiation PMID: 15724149 
Adrb2+|Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2+
involves: 129S1/Sv * 129X1/SvJ		 MGI:87938  MP:0008396 abnormal osteoclast differentiation PMID: 15724149 
Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ		 MGI:87938  MP:0004982 abnormal osteoclast morphology PMID: 15724149 
Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ		 MGI:87938  MP:0001541 abnormal osteoclast physiology PMID: 15724149 
Adrb1tm1Bkk|Adrb2tm1Bkk Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MP:0008872 abnormal physiological response to xenobiotic PMID: 10358009 
Adrb1tm1Bkk|Adrb2tm1Bkk Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MP:0003638 abnormal response/metabolism to endogenous compounds PMID: 10358009 
Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2tm1Bkk
FVB.129-Adrb2		 MGI:87938  MP:0001262 decreased body weight PMID: 10358008 
Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ		 MGI:87938  MP:0004993 decreased bone resorption PMID: 15724149 
Adrb2+|Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2+
involves: 129S1/Sv * 129X1/SvJ		 MGI:87938  MP:0004993 decreased bone resorption PMID: 15724149 
Adrb1tm1Bkk|Adrb2tm1Bkk Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MP:0005140 decreased cardiac muscle contractility PMID: 10358009 
Adrb2tm1Kry|Tg(Col1a1-cre)1Kry Adrb2tm1Kry/Adrb2tm1Kry,Tg(Col1a1-cre)1Kry/0
involves: FVB		 MGI:3041865  MGI:87938  MP:0005560 decreased circulating glucose level PMID: 19103808 
Adrb2+|Adrb2tm1Kry|Lep+|Lepob|Tg(Col1a1-cre)1Kry Adrb2tm1Kry/Adrb2+,Lepob/Lep+,Tg(Col1a1-cre)1Kry/0
involves: C57BL/6 * FVB * STOCK Mlph a Tgfa Cdh23 Ednrb		 MGI:104663  MGI:3041865  MGI:87938  MP:0005560 decreased circulating glucose level PMID: 19103808 
Adrb1tm1Bkk|Adrb2tm1Bkk Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MP:0005333 decreased heart rate PMID: 10358009 
Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2tm1Bkk
FVB.129-Adrb2		 MGI:87938  MP:0004876 decreased mean systemic arterial blood pressure PMID: 10358008 
Adrb1tm1Bkk|Adrb2tm1Bkk Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MP:0005290 decreased oxygen consumption PMID: 10358009 
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 
Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2tm1Bkk
FVB.129-Adrb2		 MGI:87938  MP:0010379 decreased respiratory quotient PMID: 10358008 
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 
Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2tm1Bkk
involves: 129S1/Sv * 129X1/SvJ		 MGI:87938  MP:0005605 increased bone mass PMID: 15724149 
Adrb2+|Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2+
involves: 129S1/Sv * 129X1/SvJ		 MGI:87938  MP:0005605 increased bone mass PMID: 15724149 
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 
Adrb2tm1Kry|Tg(Col1a1-cre)1Kry Adrb2tm1Kry/Adrb2tm1Kry,Tg(Col1a1-cre)1Kry/0
involves: FVB		 MGI:3041865  MGI:87938  MP:0002079 increased circulating insulin level PMID: 19103808 
Adrb2+|Adrb2tm1Kry|Lep+|Lepob|Tg(Col1a1-cre)1Kry Adrb2tm1Kry/Adrb2+,Lepob/Lep+,Tg(Col1a1-cre)1Kry/0
involves: C57BL/6 * FVB * STOCK Mlph a Tgfa Cdh23 Ednrb		 MGI:104663  MGI:3041865  MGI:87938  MP:0002079 increased circulating insulin level PMID: 19103808 
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 
Adrb2tm1Bkk Adrb2tm1Bkk/Adrb2tm1Bkk
FVB.129-Adrb2		 MGI:87938  MP:0002842 increased systemic arterial blood pressure PMID: 10358008 
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 
Clinically-Relevant Mutations and Pathophysiology Click here for help
Disease:  Asthma, susceptibility to
Disease Ontology: DOID:2841
OMIM: 600807
Comments:  Polymorphisms in ADRB2 are associated with susceptibility to nocturnal asthma.
Disease:  Obesity
Disease Ontology: DOID:9970
OMIM: 601665
Role:  Mutations in ADRB2 are associated with susceptibility to obesity.
Biologically Significant Variants Click here for help
Type:  Single nucleotide polymorphism
Species:  Mouse
Description:  A Thr164 -> Ile polymorphism has been identified in humans. To understand the physiological consequences of this variant, a study has been undertaken where the Thr164 -> Ile polymorphism is mimicked in transgenic mice. Results showed impaired receptor coupling to adenylyl cyclase in myocardial membranes in vitro and impaired receptor-mediated cardiac function in vivo.
References:  88
Type:  Single nucleotide polymorphism
Species:  Human
Description:  An Arg16 -> Gly polymorphism has been identified in humans, shown to depress receptor function due to increased receptor downregulation. Studies have suggested this variant may influence vasodilator responses through differences in nitric oxide generation.
In two populations of non-nocturnal and nocturnal asthmatic patients, the presence of the Arg16 -> Gly polymorphism was statistically significantly increased in the nocturnal asthmatic population. This patient population also appeared to be more susceptible to desensitization of the airways to β2-adrenoceptor agonists.
References:  33,43,89
Type:  Single nucleotide polymorphism
Species:  Human
Description:  A Gln27 -> Glu polymorphism has been identified in humans and found to cause increased isoprenaline-induced vasodilation, suggesting a role in determining vascular reactivity.
References:  28
General Comments
For a review on the β-adrenoceptor polymorphisms see reference [58].

References

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