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β2-adrenoceptor

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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 91
Mouse 7 418 18 35.1 cM Adrb2 adrenergic receptor, beta 2 4
Rat 7 418 18q12.1 Adrb2 adrenoceptor beta 2 60
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:  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:  156
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:  127
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:  67
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:  156
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:  126
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:  28
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:  126
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:  40
Image of receptor 3D structure from RCSB PDB
Description:  Irreversible agonist-β2-adrenoceptor complex. N.B. agonist utilised was a procaterol derivative containing a covalent crosslinker.
PDB Id:  3PDS
Resolution:  3.5Å
Species:  Human
References:  130
Image of receptor 3D structure from RCSB PDB
Description:  Structure of β2-adrenoceptor bound to carazolol and an intracellular allosteric antagonist.
PDB Id:  5X7D
Ligand:  carazolol
Resolution:  2.7Å
Species:  Human
References:  104
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human β2 adrenergic receptor bound to salmeterol and Nb71.
PDB Id:  6MXT
Ligand:  salmeterol
Resolution:  2.96Å
Species:  Human
References:  109
Image of receptor 3D structure from RCSB PDB
Description:  Structure of β2 adrenoceptor bound to BI167107 and an engineered nanobody
PDB Id:  4LDE
Ligand:  BI-167107
Resolution:  2.79Å
Species:  Human
References:  128
Image of receptor 3D structure from RCSB PDB
Description:  Structure of β2-adrenoceptor bound to a covalent agonist and an engineered nanobody.
PDB Id:  4QKX
Resolution:  3.3Å
Species:  Human
References:  157
Associated Proteins Click here for help
Interacting Proteins
Name Effect References
β2-adrenoceptor 6,30,69,93,114
β1-adrenoceptor 96-97,114,166
β3-adrenoceptor 30
α1D-adrenoceptor 152
α2A-adrenoceptor 93
5-HT4 receptor 25
δ receptor 88,113
κ receptor 88
μ receptor 93
EP1 receptor 112
B2 receptor 64
CXCR4 95
CB1 receptor 79,93
mouse 71 (M71) Olfactory receptor 65
D1 receptor 93
OT receptor 163-164
epidermal growth factor receptor 110
GluA1 87
AT1 receptor 19,86
A1 receptor 39
Insulin receptor 142
Natural/Endogenous Ligands Click here for help
(-)-adrenaline
(-)-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 38
⤷ pKd 11.4 (Kd 4x10-12 M) [38]
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 15
⤷ pKd 9.8 (Kd 1.44x10-10 M) [15]
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 139
⤷ pKd 5.3 (Kd 4.81x10-6 M) [139]
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 92
⤷ pKi 9.4 (Ki 4x10-10 M) [92]
salmeterol Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Partial agonist 6.8 – 9.3 pKi 14,18,46
⤷ pKi 6.8 – 9.3 [14,18,46]
zinterol Small molecule or natural product Hs Agonist 8.0 pKi 14
⤷ pKi 8.0 [14]
clenbuterol Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.4 – 7.9 pKi 14,18,90
⤷ pKi 7.4 – 7.9 [14,18,90]
indacaterol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Immunopharmacology Ligand Hs Agonist 7.4 – 7.8 pKi 21-22
⤷ pKi 7.4 – 7.8 [21-22]
BRL35135 Small molecule or natural product Hs Partial agonist 7.4 pKi 14
⤷ pKi 7.4 [14]
procaterol Small molecule or natural product Approved drug Immunopharmacology Ligand Hs Agonist 7.1 pKi 14
⤷ pKi 7.1 [14]
ractopamine Small molecule or natural product Hs Partial agonist 6.6 – 6.9 pKi 14,46,82
⤷ pKi 6.6 – 6.9 [14,46,82]
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 – 6.6 pKi 14-15,134
⤷ pKi 6.4 – 6.6 [14-15,134]
BRL 37344 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 6.5 pKi 14
⤷ pKi 6.5 [14]
fenoterol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Agonist 5.5 – 7.0 pKi 9,14,18,46
⤷ pKi 5.5 – 7.0 [9,14,18,46]
(-)-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 14,54,74,84
⤷ pKi 6.0 – 6.2 [14,54,74,84]
salbutamol Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Partial agonist 5.3 – 6.1 pKi 13-14,18,46,82,138
⤷ pKi 5.3 – 6.1 [13-14,18,46,82,138]
ephedrine Small molecule or natural product Approved drug Primary target of this compound Hs Partial agonist 5.6 pKi 84
⤷ pKi 5.6 [84]
terbutaline Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Partial agonist 5.5 – 5.6 pKi 13-14
⤷ pKi 5.5 – 5.6 [13-14]
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 101
⤷ pKi 5.4 [101]
(-)-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 – 5.4 pKi 14,54,74
⤷ pKi 4.6 – 5.4 [14,54,74]
olodaterol Small molecule or natural product Approved drug Primary target of this compound Ligand has a PDB structure Immunopharmacology Ligand Hs Agonist 10.0 pEC50 29
⤷ pEC50 10.0 (IC50 1x10-10 M) [29]
BI-167107 Small molecule or natural product Click here for species-specific activity table Hs Agonist 10.0 pEC50 73
⤷ pEC50 10.0 (EC50 1x10-10 M) [73]
Description: Determined in an intracellular cAMP accumulation assay in CHO-K1 cells expressing hβ2-AR
salmeterol Small molecule or natural product Approved drug Immunopharmacology Ligand Hs Partial agonist 9.2 – 9.9 pEC50 14,21
⤷ pEC50 9.2 – 9.9 [14,21]
zinterol Small molecule or natural product Hs Agonist 9.5 pEC50 14
⤷ pEC50 9.5 [14]
vilanterol Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Agonist 9.4 pEC50 123
⤷ pEC50 9.4 (EC50 3.98x10-10 M) [123]
clenbuterol Small molecule or natural product Click here for species-specific activity table Hs Agonist 9.2 pEC50 14
⤷ pEC50 9.2 [14]
formoterol 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 – 10.1 pEC50 3,14,18,21,103
⤷ pEC50 7.8 – 10.1 [3,14,18,21,103]
BRL35135 Small molecule or natural product Hs Partial agonist 8.7 pEC50 14
⤷ pEC50 8.7 [14]
procaterol Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Agonist 8.4 pEC50 14
⤷ pEC50 8.4 [14]
isoprenaline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 8.2 pEC50 14-15
⤷ pEC50 8.2 [14-15]
indacaterol Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Agonist 8.1 pEC50 21
⤷ pEC50 8.1 [21]
(-)-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 7.9 pEC50 14
⤷ pEC50 7.9 [14]
ractopamine Small molecule or natural product Hs Partial agonist 7.6 – 7.8 pEC50 14,46
⤷ pEC50 7.6 – 7.8 [14,46]
fenoterol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 6.1 – 8.9 pEC50 14,46
⤷ pEC50 6.1 – 8.9 [14,46]
terbutaline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 7.3 pEC50 14
⤷ pEC50 7.3 [14]
salbutamol Small molecule or natural product Approved drug Immunopharmacology Ligand Hs Partial agonist 6.3 – 7.7 pEC50 14,46
⤷ pEC50 6.3 – 7.7 [14,46]
BRL 37344 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 6.9 pEC50 14
⤷ pEC50 6.9 [14]
(-)-noradrenaline Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist 6.4 pEC50 14
⤷ pEC50 6.4 [14]
solabegron Small molecule or natural product Click here for species-specific activity table Hs Agonist 5.9 pEC50 153
⤷ pEC50 5.9 [153]
mirabegron Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Hs Agonist <5.0 – 5.2 pEC50 47,146
⤷ pEC50 5.0 – 5.2 [47,146]
pEC50 <5.0 (EC50 >1x10-5 M) [146]
mirabegron Small molecule or natural product Approved drug Click here for species-specific activity table Ligand has a PDB structure Rn Agonist 5.0 pEC50 47
⤷ pEC50 5.0 [47]
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 7
⤷ pIC50 9.2 (IC50 6x10-10 M) [7]
Description: Membrane radioligand displacement assay using [3H]CGP12177 as tracer.
cimaterol Small molecule or natural product Click here for species-specific activity table Hs Agonist - - 14
⤷ [14]
View species-specific agonist tables
Agonist Comments
Although [138] states that salbutamol was tested, in fact R-(-)salbutamol (levosalbutamol) was tested. pKi values are from binding studies and pEC50 from functional studies (usually cAMP generation) which give a better idea of relative experimental or clinical potency. Salbutamol, terbutaline and fenoterol are examples of short acting β agonists (SABAs), salmeterol and formoterol are long acting β agonists (LABAs) and indacaterol, olodaterol abediterol and vilanterol are ultra long acting β agonists (ultra-LABAs) [26]. BRL37344 and BRL35135 are classified as β3-AR selective agonists (rodent selective) but have significant actions at β2-AR [118]. Clenbuterol is included on the World Anti-Doping Authority's list of banned substances due to its popularity as a drug used by bodybuilders and for weight loss. Clinical uses: β2-AR agonists are widely used in asthma and COPD. Adrenaline is used as a bolus injection in cardiac arrest, anaphylaxis and as an intravenous infusion for shock.
Antagonists
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Ligand Sp. Action Value Parameter Reference
butoxamine Small molecule or natural product Rn Antagonist 6.4 pKB 72
⤷ pKB 6.4 (KB 3.55x10-7 M) [72]
butoxamine Small molecule or natural product Hs Antagonist 6.2 – 6.5 pKB 14,32,149
⤷ pKB 6.2 – 6.5 [14,32,149]
[125I]ICYP Small molecule or natural product Click here for species-specific activity table Ligand is labelled Ligand is radioactive Hs Antagonist 11.1 – 11.4 pKd 108,134,145
⤷ pKd 11.1 – 11.4 (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. [108,134,145]
7-methylcyanopindolol Small molecule or natural product Click here for species-specific activity table Ligand has a PDB structure Hs Inverse agonist 10.4 pKd 133
⤷ pKd 10.4 [133]
[3H]dihydroalprenolol Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 10.1 pKd 145
⤷ pKd 10.1 [145]
[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 15
⤷ pKd 9.8 [15]
carazolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.9 – 10.5 pKi 14,131
⤷ pKi 9.9 – 10.5 [14,131]
timolol 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 Antagonist 9.7 pKi 13
⤷ pKi 9.7 [13]
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 13,36
⤷ pKi 9.4 – 9.9 [13,36]
pindolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.4 pKi 92
⤷ pKi 9.4 [92]
CGP 12177 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.4 pKi 13,15,108
⤷ pKi 9.4 [13,15,108]
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 13,17,108
⤷ pKi 9.2 – 9.5 [13,17,108]
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 13,17,82,108
⤷ pKi 9.1 – 9.5 [13,17,82,108]
bunolol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 9.3 pKi 10
⤷ pKi 9.3 (Ki 5.5x10-10 M) [10]
bupranolol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 8.3 – 9.9 pKi 13,36,108
⤷ pKi 8.3 – 9.9 [13,36,108]
alprenolol Small molecule or natural product Approved drug Primary target of this compound Hs Partial agonist 9.0 pKi 13
⤷ pKi 9.0 [13]
SR59230A Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.5 – 9.3 pKi 13,36
⤷ pKi 8.5 – 9.3 [13,36]
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 10,13
⤷ pKi 8.0 (Ki 1.1x10-8 M) [10,13]
nebivolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.9 – 8.0 pKi 14,52
⤷ pKi 7.9 – 8.0 [14,52]
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 13,36
⤷ pKi 7.0 – 8.6 [13,36]
betaxolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.2 – 8.2 pKi 14,108,136
⤷ pKi 7.2 – 8.2 [14,108,136]
NIP Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.5 pKi 108
⤷ pKi 7.5 [108]
propafenone Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.4 pKi 10
⤷ pKi 7.4 (Ki 3.6x10-8 M) [10]
sotalol Small molecule or natural product Approved drug Primary target of this compound Click here for species-specific activity table Hs Antagonist 6.5 – 6.9 pKi 10,13
⤷ pKi 6.5 – 6.9 [10,13]
metoprolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.3 – 6.9 pKi 13,108
⤷ pKi 6.3 – 6.9 [13,108]
butoxamine Small molecule or natural product Rn Antagonist 6.3 – 6.5 pKi 32,149
⤷ pKi 6.3 – 6.5 (Ki 4.68x10-7 – 3.09x10-7 M) [32,149]
cicloprolol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pKi 108
⤷ pKi 6.2 [108]
NIHP Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.0 pKi 108
⤷ pKi 6.0 [108]
atenolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 5.6 – 6.0 pKi 13,108
⤷ pKi 5.6 – 6.0 [13,108]
LK 204-545 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.2 pKi 108
⤷ pKi 5.2 [108]
View species-specific antagonist tables
Antagonist Comments
The approved drug propranolol is categorised as a non-selective β-adrenoceptor antagonist but is slightly selective for β2-AR and has very low affinity for β3-AR. Propranolol also behaves as a biased agonist in several studies- an inverse agonist decreasing cAMP whilst stimulating β-arrestin and gene transcription [11,16]. Carvedilol is a non-selective β-AR and α1-AR antagonist used to treat cardiac failure. Carvedilol has been suggested to be a β-arrestin biased agonist [161] but this characteristic has been challenged [23] with evidence supporting low efficacy activation of Gs coupled β2-adrenoceptors as the explanation. Several 'cardioselective' or β1-AR selective antagonists such as atenolol and metoprolol have appreciable affinity for β2-AR. Several antagonists may display partial agonist activity at β2-AR including pindolol, carazolol, bucindolol, nebivolol and carvedilol [14] in assays where there is significant receptor reserve or receptor over-expression. ICI118551 is the most selective β2-AR antagonist currently available but is only used in in vitro studies where it displays ~300 fold selectivity vs. the other 8 adrenoceptor subtypes. Although often described as a β3-AR selective antagonist, SR59230A has little selectivity and is a high affinity antagonist at β2-AR [115]. The main action of propafenone is to block voltage gated Na+ channels (see the Voltage-gated sodium channels family in the Ion Channels section of this website for further details) but is also a weak β-adrenoceptor antagonist. Some cell systems (e.g. HEK cells) commonly used to study the pharmacology of β-AR subtypes express functionally active β2-AR populations. Clinical uses: not directly used, but effects of several β-AR antagonists used clinically (see β1-AR) are also likely to occur through β2-AR (e.g. migraine, portal hypertension, anxiety, glaucoma, thyrotoxicosis, infantile haemangioma).
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 143-144
⤷ pKi 5.3 [143-144]
Zn2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Negative 3.3 pKi 143-144
⤷ pKi 3.3 [143-144]
AS408 Small molecule or natural product Ligand has a PDB structure N/A - - - 105
⤷ [105]
compound 6 [PMID: 29769246] Small molecule or natural product Hs Positive - - 121
⤷ cooperativity [121]
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 [143-144]. Cmpd-6 is a positive allosteric modulator of the pharmacological activity of carvedilol at the β2-AR [121].
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 [48].
There is a large literature on the role of autoantibodies to β2-AR associated with a variety of disease processes [31,37,75,78,160].
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:  12
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   dendritic cell (CL:0000451)
Comment:  β2-AR agonist-exposed mature dendritic cells have a reduced ability to cross-present protein antigens while retaining exogenous peptide presentation capability. This effect is mediated through a Gi/o inhibitory pathway.
References:  70
Immuno Cell Type:  T cells
Cell Ontology Term:   CD8-positive, alpha-beta T cell (CL:0000625)
regulatory T cell (CL:0000815)
Comment:  Activation of β2-ARs enhances retention-promoting signals through CCR7 and CXCR4 and inhibits lymphocyte (T cells and other lymphocyte lineages) egress from lymph nodes. In models of T cell-mediated inflammatory diseases, β2-AR-mediated signals inhibit lymph node egress of antigen-primed T cells and reduce their recruitment into peripheral tissues [119].CD8+ T cells (CL:0000625): CD8+ T cells from patients with rheumatoid arthritis express lower levels of β2-ARs compared with healthy subjects [12].
Treg cells (CL:0000815): β2-AR agonist increases Treg-cell suppressive function associated with decreased IL-2 mRNA levels in responder CD4+ T cells and improved Treg-cell-induced conversion of CD4+ Foxp3- cells into Foxp3+ induced Treg cells [62].
References:  12,62
Immuno Cell Type:  Mast cells
Cell Ontology Term:   mast cell (CL:0000097)
Comment:  Mast cell histamine release was increased in coculture with human airways smooth muscle cells and this was enhanced by β2-AR agonists. Inhibition of mast cell mediator release by β2-AR-agonists was reduced in coculture. β2-AR agonists did not prevent smooth muscle cell contraction when mast cells were present, but this was reversed by corticosteroids.
References:  99
Immuno Cell Type:  Macrophages & monocytes
Cell Ontology Term:   macrophage (CL:0000235)
monocyte (CL:0000576)
Comment:  Monocytes (CL:0000576): Monocytes from patients with rheumatoid arthritis express lower levels of β2-ARs compared with healthy subjects [12]. Monocytes from high-fat diet-induced obese mice presented higher expression levels of pro-inflammatory cytokines and a higher % of monocytes with a pro-inflammatory phenotype than those from lean animals. β2-AR stimulation induced a shift towards an anti-inflammatory activity profile and phenotype in obese mice, whereas it induced a shift towards a pro-inflammatory activity profile and phenotype in lean mice [55]. Treatment of monocytes with the β2-AR agonist clenbuterol inhibits differentiation into dendritic cells, reduces the % of CD1a+ immature DCs, while increasing the frequency of monocytes retaining CD14 surface expression [59].
Macrophages (CL:0000235): Immune cell β2-ARs are important for proinflammatory macrophage infiltration to the heart in a chronic isoprenaline administration model of heart failure. Mice lacking immune cell β2-AR have decreased proinflammatory macrophage infiltration to the heart, decreased cardiac injury and cardiomyocyte death, decreased interstitial fibrosis and hypertrophy and improved function [147].
References:  12,55,59,147
Immuno Process Associations
Immuno Process:  Antigen presentation
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling
Immuno Process:  Inflammation
Primary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gs family
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. In skeletal muscle cAMP signalling is associated with mTORC2 activation that promotes GLUT4 translocation and increased glucose uptake.
References:  100,135,140,159
Secondary Transduction Mechanisms Click here for help
Transducer Effector/Response
Gi/Go family Guanylate cyclase stimulation
Comments:  Adenylyl cyclase inhibition reduces the conversion of ATP to cAMP. Stimulation of guanylyl cyclase (GC) causes an increase in cGMP levels, and subsequent activation of protein kinase G.
References:  100,162
Tissue Distribution Click here for help
55 organs and tissues.
Species:  Human
Technique:  RNA expression.
References:  20
Heart: right atrial appendage, left atrial free wall, left ventricular papillary muscle and pericardium, atrioventricular node, bundle of His, interatrial and interventricular septa, right atrium, left ventricular free wall, right ventricular free wall, right atrium from an area near the atrioventricular node and cardiac nerves. Intimal surface of coronary arteries.
Species:  Human
Technique:  Autoradiography
References:  34,49,141
Lung >> spleen > kidney > heart > brain > skeletal muscle > liver.
Species:  Mouse
Technique:  Radioligand binding.
References:  5
Brain: medial prefrontal cortex.
Species:  Mouse
Technique:  Immunohistochemistry in GABAergic interneurons in medial prefrontal cortex, including parvalbumin (PV)-, calretinin (CR)-, calbindin D-28k (CB)-, somatostatin (SST)- and reelin-immunoreactive (ir) interneurons. β2-AR most likely in SSTR-ir neurons.
References:  106
Lung >> skeletal muscle > spleen > kidney > heart > brain > liver.
Species:  Mouse
Technique:  in situ hybridisation.
References:  5
Lung > heart.
Species:  Rat
Technique:  Radioligand binding.
References:  116
Subcellular distribution in ventricular myocytes.
Species:  Rat
Technique:  Ventricular myocytes and detubulated myocytes: Ca2+ transients and cell shortening: β2-AR at surface sarcolemma.
References:  44
Diabetic heart.
Species:  Rat
Technique:  Radioligand binding, western blot, mRNA.
References:  50,66
Brain: Caudate, cortex, cerebellum, hippocampus, diencephalon.
Species:  Rat
Technique:  Radioligand binding.
References:  116
Internal anal sphincter (IAS) smooth muscle.
Species:  Rat
Technique:  Western blotting.
References:  100
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
GTPase activity.
Species:  Human
Tissue:  HEK293 cells.
Response measured:  GTP hydrolysis using chemiluminescence-based GTPase-Glo Assay (Promega)
References:  2
Measurement of cAMP levels in CHO-K1 cells expressing the human β2 receptor.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  cAMP accumulation.
References:  134
Measurement of cAMP levels in rat heart and lung tissue.
Species:  Rat
Tissue:  Heart and lung.
Response measured:  cAMP accumulation.
References:  116
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:  83
Measurement of cAMP levels in Sf9 insect cells transfected with the human β2-adrenoceptor.
Species:  Human
Tissue:  Sf9 cells.
Response measured:  cAMP accumulation.
References:  135
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:  35
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:  165
Measurement of LPS-induced cytokine release (TNFα and Il-10) from human U937 macrophage cells when treated with a β2-adrenoceptor agonist.
Species:  Human
Tissue:  U937 cells.
Response measured:  Inhibition of TNFα release, stimulation of Il-10 release.
References:  83
β-arrestin recruitment.
Species:  Human
Tissue:  HEK293 cells.
Response measured:  Interaction monitored using BRET between β-arrestin2-GFP10 and β2-AR-RlucII.
References:  81
cAMP production in skeletal muscle.
Species:  Rat
Tissue:  L6 skeletal muscle cells.
Response measured:  cAMP accumulation using antibody-based flashplate assay.
References:  120
Measurement of cAMP levels in rat heart and lung tissue.
Species:  Rat
Tissue:  Heart and lung.
Response measured:  cAMP accumulation.
References:  116
Measurement of cAMP levels in CHO-K1 cells expressing the human β2 receptor.
Species:  Human
Tissue:  CHO-K1 cells.
Response measured:  Whole cell binding using [3H]CGP12177, cAMP accumulation.
References:  14
β2-adrenoceptor agonist profiling reveals biased signalling phenotypes for the β2-adrenoceptor with possible implications for the treatment of asthma.
Species:  Human
Tissue:  Glo-sensor cAMP accumulation, pathhunter β-arrestin recruitment, BRET G protein recruitment, ERK1/2 phosphorylation, receptor internalization and endosomal localisation.
Response measured:  HEK293 cells expressing human β2-AR.
References:  46
Measurement of cAMP levels in HEK-293 cell lines expressing the Glosensor (Promega) cAMP reporter, the ICUE2 cAMP reporter and the human β2-AR .
Species:  Human
Tissue:  HEK293 cells.
Response measured:  cAMP accumulation measured using chemiluminescence-based cAMP biosensor.
References:  2
β-arrestin recruitment and endocytosis.
Species:  Human
Tissue:  HEK293 cells.
Response measured:  Recruitment monitored using PathHunter, a chemiluminescence-based enzyme fragment complementation assay: endocytosis measured by active endocytosis assay (DiscoverX).
References:  2
Intracellular Ca2+ mobilisation involving PLC and IP3 but not cAMP, Gαs or Gαi.
Species:  Human
Tissue:  HEK293 cells endogenously expressing β2-AR.
Response measured:  Fluorescence-based Ca2+ flux assays
References:  56
Receptor heteromer formation.
Species:  Human
Tissue:  HEK293 cells.
Response measured:  Interaction between GPCRs monitored using BRET.
References:  86
Measurement of cAMP levels in HEK-293 cells using a FRET based biosensor.
Species:  Human
Tissue:  HEK293 cells.
Response measured:  cAMP accumulation measured using FRET-based cAMP biosensor.
References:  155
Glucose uptake in skeletal muscle.
Species:  Rat
Tissue:  L6 skeletal muscle cells.
Response measured:  Glucose uptake measured using [3H]2-deoxyglucose.
References:  132
Physiological Functions Click here for help
Stimulation of aqueous humor formation and outflow.
Species:  Human
Tissue:  Eye.
References:  122
Hypotension, lowering of blood pressure.
Species:  Mouse
Tissue:  Blood vessels.
References:  41
Presynaptic facilitation of noradrenlaine release from sympathetic nerves.
Species:  Rat
Tissue:  Isolated perfused kidney.
References:  94
Bronchodilation.
Species:  Mouse
Tissue:  Lung.
References:  35
Uterine relaxation.
Species:  Human
Tissue:  Myometrial muscle.
References:  107
Inhibition of apoptosis via a PTX-sensitive G-protein.
Apoptosis via Gs and adenylyl cyclase.
Species:  Rat
Tissue:  Ventricular cardiomyocytes.
References:  125
Synaptic plasticity and memory.
Species:  Mouse
Tissue:  Brain.
References:  45,57,68,85
Coronary vasodilation.
Species:  Human
Tissue:  Coronary blood vessels.
References:  124,154
Positive inotropic, chronotropic and lusitropic effects in atria.
Species:  Human
Tissue:  Right atrial appendage.
References:  117
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:  100
Cardioprotective effects.
Species:  Mouse
Tissue:  Cardiomyocytes from mice with chemically induced cardiotoxicity.
References:  24,137
Glucose release from liver.
Species:  Human
Tissue:  Liver.
References:  33,63
Modulation of kidney function in humans and other animals.
Species:  Human
Tissue:  Kidney.
References:  89
Bronchodilation in human and other animals.
Species:  Human
Tissue:  Lung.
References:  158
Glucose uptake in skeletal muscle.
Species:  Rat
Tissue:  L6 skeletal muscle cells.
References:  132
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:  71
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:  41
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:  111
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:  129
β2-AR knockout mice show limited T cell autoimmunity in EAE through a mechanism mediated by the suppression of IL-2, IFN-γ, and GM-CSF production via inducible cAMP early repressor (ICER).
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  8
β1-/β2-AR knockout mice show an enhanced inflammatory response to injury, that delayed early muscle regeneration, but enhanced myoblast proliferation later during regeneration to produce a similar functional recovery to controls by 14 days post-injury.
Species:  Mouse
Tissue:  Skeletal muscle.
Technique:  Gene targeting in embryonic stem cells.
References:  42
β2-AR knockout mice do not develop muscle LIM protein cardiomyopathy due to positive modulation of Ca2+ due to removal of inhibitory Gisignaling and increased phosphorylation of troponin I and phospholamban.
Species:  Mouse
Tissue:  Heart.
Technique: 
References:  42
β2-AR knockout mice show preserved cold- and diet-induced adaptive thermogenesis but disrupted glucose homeostasis possibly by accelerating hepatic glucose production and insulin secretion.
Species:  Mouse
Tissue:  Metabolism.
Technique:  Gene targeting in embryonic stem cells.
References:  51
Immune cell-expressed β2-AR play an essential role in regulating the early inflammatory repair response to acute myocardial injury by facilitating cardiac leukocyte infiltration.
Species:  Mouse
Tissue:  Heart.
Technique:  Gene targeting in embryonic stem cells.
References:  61
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:  150
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:  58,76,102,151
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Arg16 > Gly polymorphism and the Thr164 > Ile polymorphism are associated with an increased risk of severe exacerbations in patients with chronic obstructive pulmonary disease.
References:  80,148
Type:  Single nucleotide polymorphism
Species:  Human
Description:  β2-AR polymorphisms are associated with changes in body composition and obesity. The Gln27> Glu polymorphism is associated with obesity and the Arg16> Gly polymorphism with lean mass in men and the development of obesity.
References:  77
Type:  Single nucleotide polymorphism
Species:  Human
Description:  The Arg16 > Gly polymorphism is associated with an increased risk of severe adverse events in children treated with long acting β2-AR agonists.
References:  27,167
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:  43,53
General Comments
For a review on the β-adrenoceptor polymorphisms see reference [98].

References

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