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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

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 90
Mouse 7 418 18 35.1 cM Adrb2 adrenergic receptor, beta 2 4
Rat 7 418 18q12.1 Adrb2 adrenoceptor beta 2 59
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
ChEMBL Target
DrugBank Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
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:  155
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:  126
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:  66
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:  155
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:  125
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:  27
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:  125
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:  39
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:  129
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:  103
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:  108
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:  127
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:  156
Associated Proteins Click here for help
Interacting Proteins
Name Effect References
β2-adrenoceptor 6,29,68,92,113
β1-adrenoceptor 95-96,113,165
β3-adrenoceptor 29
α1D-adrenoceptor 151
α2A-adrenoceptor 92
5-HT4 receptor 24
δ receptor 87,112
κ receptor 87
μ receptor 92
EP1 receptor 111
B2 receptor 63
CXCR4 94
CB1 receptor 78,92
mouse 71 (M71) Olfactory receptor 64
D1 receptor 92
OT receptor 162-163
epidermal growth factor receptor 109
GluA1 86
AT1 receptor 18,85
A1 receptor 38
Insulin receptor 141
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 37
pKd 11.4 (Kd 4x10-12 M) [37]
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 14
pKd 9.8 (Kd 1.44x10-10 M) [14]
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 138
pKd 5.3 (Kd 4.81x10-6 M) [138]
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 91
pKi 9.4 (Ki 4x10-10 M) [91]
salmeterol Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Partial agonist 6.8 – 9.3 pKi 13,17,45
pKi 6.8 – 9.3 [13,17,45]
zinterol Small molecule or natural product Hs Agonist 8.0 pKi 13
pKi 8.0 [13]
clenbuterol Small molecule or natural product Click here for species-specific activity table Hs Full agonist 7.4 – 7.9 pKi 13,17,89
pKi 7.4 – 7.9 [13,17,89]
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 20-21
pKi 7.4 – 7.8 [20-21]
BRL35135 Small molecule or natural product Hs Partial agonist 7.4 pKi 13
pKi 7.4 [13]
procaterol Small molecule or natural product Approved drug Immunopharmacology Ligand Hs Agonist 7.1 pKi 13
pKi 7.1 [13]
ractopamine Small molecule or natural product Hs Partial agonist 6.6 – 6.9 pKi 13,45,81
pKi 6.6 – 6.9 [13,45,81]
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 13-14,133
pKi 6.4 – 6.6 [13-14,133]
BRL 37344 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 6.5 pKi 13
pKi 6.5 [13]
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 9,13,17,45
pKi 5.5 – 7.0 [9,13,17,45]
(-)-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 13,53,73,83
pKi 6.0 – 6.2 [13,53,73,83]
salbutamol Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Partial agonist 5.3 – 6.1 pKi 12-13,17,45,81,137
pKi 5.3 – 6.1 [12-13,17,45,81,137]
ephedrine Small molecule or natural product Approved drug Primary target of this compound Hs Partial agonist 5.6 pKi 83
pKi 5.6 [83]
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 12-13
pKi 5.5 – 5.6 [12-13]
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 100
pKi 5.4 [100]
(-)-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 13,53,73
pKi 4.6 – 5.4 [13,53,73]
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 28
pEC50 10.0 (IC50 1x10-10 M) [28]
BI-167107 Small molecule or natural product Click here for species-specific activity table Hs Agonist 10.0 pEC50 72
pEC50 10.0 (EC50 1x10-10 M) [72]
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 13,20
pEC50 9.2 – 9.9 [13,20]
zinterol Small molecule or natural product Hs Agonist 9.5 pEC50 13
pEC50 9.5 [13]
vilanterol Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Agonist 9.4 pEC50 122
pEC50 9.4 (EC50 3.98x10-10 M) [122]
clenbuterol Small molecule or natural product Click here for species-specific activity table Hs Agonist 9.2 pEC50 13
pEC50 9.2 [13]
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 3,13,17,20,102
pEC50 7.8 – 10.1 [3,13,17,20,102]
BRL35135 Small molecule or natural product Hs Partial agonist 8.7 pEC50 13
pEC50 8.7 [13]
procaterol Small molecule or natural product Approved drug Primary target of this compound Immunopharmacology Ligand Hs Agonist 8.4 pEC50 13
pEC50 8.4 [13]
isoprenaline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Full agonist 8.2 pEC50 13-14
pEC50 8.2 [13-14]
indacaterol Small molecule or natural product Approved drug Click here for species-specific activity table Immunopharmacology Ligand Hs Agonist 8.1 pEC50 20
pEC50 8.1 [20]
(-)-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 13
pEC50 7.9 [13]
ractopamine Small molecule or natural product Hs Partial agonist 7.6 – 7.8 pEC50 13,45
pEC50 7.6 – 7.8 [13,45]
fenoterol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Agonist 6.1 – 8.9 pEC50 13,45
pEC50 6.1 – 8.9 [13,45]
terbutaline Small molecule or natural product Approved drug Click here for species-specific activity table Hs Partial agonist 7.3 pEC50 13
pEC50 7.3 [13]
salbutamol Small molecule or natural product Approved drug Immunopharmacology Ligand Hs Partial agonist 6.3 – 7.7 pEC50 13,45
pEC50 6.3 – 7.7 [13,45]
BRL 37344 Small molecule or natural product Click here for species-specific activity table Hs Partial agonist 6.9 pEC50 13
pEC50 6.9 [13]
(-)-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 13
pEC50 6.4 [13]
solabegron Small molecule or natural product Click here for species-specific activity table Hs Agonist 5.9 pEC50 152
pEC50 5.9 [152]
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 46,145
pEC50 5.0 – 5.2 [46,145]
pEC50 <5.0 (EC50 >1x10-5 M) [145]
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 46
pEC50 5.0 [46]
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 - - 13
[13]
View species-specific agonist tables
Agonist Comments
Although [137] 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) [25]. BRL37344 and BRL35135 are classified as β3-AR selective agonists (rodent selective) but have significant actions at β2-AR [117]. 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.
Antagonists
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Ligand Sp. Action Value Parameter Reference
butoxamine Small molecule or natural product Rn Antagonist 6.4 pKB 71
pKB 6.4 (KB 3.55x10-7 M) [71]
butoxamine Small molecule or natural product Hs Antagonist 6.2 – 6.5 pKB 13,31,148
pKB 6.2 – 6.5 [13,31,148]
[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 107,133,144
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. [107,133,144]
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 132
pKd 10.4 [132]
[3H]dihydroalprenolol Small molecule or natural product Ligand is labelled Ligand is radioactive Hs Antagonist 10.1 pKd 144
pKd 10.1 [144]
[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 14
pKd 9.8 [14]
carazolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.9 – 10.5 pKi 13,130
pKi 9.9 – 10.5 [13,130]
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 12
pKi 9.7 [12]
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 12,35
pKi 9.4 – 9.9 [12,35]
pindolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 9.4 pKi 91
pKi 9.4 [91]
CGP 12177 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 9.4 pKi 12,14,107
pKi 9.4 [12,14,107]
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 12,16,107
pKi 9.2 – 9.5 [12,16,107]
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 12,16,81,107
pKi 9.1 – 9.5 [12,16,81,107]
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 12,35,107
pKi 8.3 – 9.9 [12,35,107]
alprenolol Small molecule or natural product Approved drug Primary target of this compound Hs Partial agonist 9.0 pKi 12
pKi 9.0 [12]
SR59230A Small molecule or natural product Click here for species-specific activity table Hs Antagonist 8.5 – 9.3 pKi 12,35
pKi 8.5 – 9.3 [12,35]
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 10,12
pKi 8.0 (Ki 1.1x10-8 M) [10,12]
nebivolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.9 – 8.0 pKi 13,51
pKi 7.9 – 8.0 [13,51]
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 12,35
pKi 7.0 – 8.6 [12,35]
betaxolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 7.2 – 8.2 pKi 13,107,135
pKi 7.2 – 8.2 [13,107,135]
NIP Small molecule or natural product Click here for species-specific activity table Hs Antagonist 7.5 pKi 107
pKi 7.5 [107]
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 10,12
pKi 6.5 – 6.9 [10,12]
metoprolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 6.3 – 6.9 pKi 12,107
pKi 6.3 – 6.9 [12,107]
butoxamine Small molecule or natural product Rn Antagonist 6.3 – 6.5 pKi 31,148
pKi 6.3 – 6.5 (Ki 4.68x10-7 – 3.09x10-7 M) [31,148]
cicloprolol Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.2 pKi 107
pKi 6.2 [107]
NIHP Small molecule or natural product Click here for species-specific activity table Hs Antagonist 6.0 pKi 107
pKi 6.0 [107]
atenolol Small molecule or natural product Approved drug Click here for species-specific activity table Hs Antagonist 5.6 – 6.0 pKi 12,107
pKi 5.6 – 6.0 [12,107]
LK 204-545 Small molecule or natural product Click here for species-specific activity table Hs Antagonist 5.2 pKi 107
pKi 5.2 [107]
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 [15]. 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 [160] but this characteristic has been challenged [22] 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 and nebivolol [13] 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 [114]. 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.
Allosteric Modulators
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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 142-143
pKi 5.3 [142-143]
Zn2+ Click here for species-specific activity table Ligand is endogenous in the given species Hs Negative 3.3 pKi 142-143
pKi 3.3 [142-143]
AS408 Small molecule or natural product Ligand has a PDB structure N/A - - - 104
[104]
compound 6 [PMID: 29769246] Small molecule or natural product Hs Positive - - 120
cooperativity [120]
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 [142-143]. Cmpd-6 is a positive allosteric modulator of the pharmacological activity of carvedilol at the β2-AR [120].
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 [47].
There is a large literature on the role of autoantibodies to β2-AR associated with a variety of disease processes [30,36,74,77,159].
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:  11
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:  69
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 [118].CD8+ T cells (CL:0000625): CD8+ T cells from patients with rheumatoid arthritis express lower levels of β2-ARs compared with healthy subjects [11].
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 [61].
References:  11,61
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:  98
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 [11]. 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 [54]. 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 [58].
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 [146].
References:  11,54,58,146
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:  99,134,139,158
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:  99,161
Tissue Distribution Click here for help
55 organs and tissues.
Species:  Human
Technique:  RNA expression.
References:  19
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:  33,48,140
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:  105
Lung >> skeletal muscle > spleen > kidney > heart > brain > liver.
Species:  Mouse
Technique:  in situ hybridisation.
References:  5
Lung > heart.
Species:  Rat
Technique:  Radioligand binding.
References:  115
Subcellular distribution in ventricular myocytes.
Species:  Rat
Technique:  Ventricular myocytes and detubulated myocytes: Ca2+ transients and cell shortening: β2-AR at surface sarcolemma.
References:  43
Diabetic heart.
Species:  Rat
Technique:  Radioligand binding, western blot, mRNA.
References:  49,65
Brain: Caudate, cortex, cerebellum, hippocampus, diencephalon.
Species:  Rat
Technique:  Radioligand binding.
References:  115
Internal anal sphincter (IAS) smooth muscle.
Species:  Rat
Technique:  Western blotting.
References:  99
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:  133
Measurement of cAMP levels in rat heart and lung tissue.
Species:  Rat
Tissue:  Heart and lung.
Response measured:  cAMP accumulation.
References:  115
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:  82
Measurement of cAMP levels in Sf9 insect cells transfected with the human β2-adrenoceptor.
Species:  Human
Tissue:  Sf9 cells.
Response measured:  cAMP accumulation.
References:  134
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:  34
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:  164
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:  82
β-arrestin recruitment.
Species:  Human
Tissue:  HEK293 cells.
Response measured:  Interaction monitored using BRET between β-arrestin2-GFP10 and β2-AR-RlucII.
References:  80
cAMP production in skeletal muscle.
Species:  Rat
Tissue:  L6 skeletal muscle cells.
Response measured:  cAMP accumulation using antibody-based flashplate assay.
References:  119
Measurement of cAMP levels in rat heart and lung tissue.
Species:  Rat
Tissue:  Heart and lung.
Response measured:  cAMP accumulation.
References:  115
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:  13
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:  45
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:  55
Receptor heteromer formation.
Species:  Human
Tissue:  HEK293 cells.
Response measured:  Interaction between GPCRs monitored using BRET.
References:  85
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:  154
Glucose uptake in skeletal muscle.
Species:  Rat
Tissue:  L6 skeletal muscle cells.
Response measured:  Glucose uptake measured using [3H]2-deoxyglucose.
References:  131
Physiological Functions Click here for help
Stimulation of aqueous humor formation and outflow.
Species:  Human
Tissue:  Eye.
References:  121
Hypotension, lowering of blood pressure.
Species:  Mouse
Tissue:  Blood vessels.
References:  40
Presynaptic facilitation of noradrenlaine release from sympathetic nerves.
Species:  Rat
Tissue:  Isolated perfused kidney.
References:  93
Bronchodilation.
Species:  Mouse
Tissue:  Lung.
References:  34
Uterine relaxation.
Species:  Human
Tissue:  Myometrial muscle.
References:  106
Inhibition of apoptosis via a PTX-sensitive G-protein.
Apoptosis via Gs and adenylyl cyclase.
Species:  Rat
Tissue:  Ventricular cardiomyocytes.
References:  124
Synaptic plasticity and memory.
Species:  Mouse
Tissue:  Brain.
References:  44,56,67,84
Coronary vasodilation.
Species:  Human
Tissue:  Coronary blood vessels.
References:  123,153
Positive inotropic, chronotropic and lusitropic effects in atria.
Species:  Human
Tissue:  Right atrial appendage.
References:  116
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:  99
Cardioprotective effects.
Species:  Mouse
Tissue:  Cardiomyocytes from mice with chemically induced cardiotoxicity.
References:  23,136
Glucose release from liver.
Species:  Human
Tissue:  Liver.
References:  32,62
Modulation of kidney function in humans and other animals.
Species:  Human
Tissue:  Kidney.
References:  88
Bronchodilation in human and other animals.
Species:  Human
Tissue:  Lung.
References:  157
Glucose uptake in skeletal muscle.
Species:  Rat
Tissue:  L6 skeletal muscle cells.
References:  131
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:  70
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:  40
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:  110
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:  128
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:  41
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:  41
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:  50
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:  60
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: