Top ▲

β2-adrenoceptor

Click here for help

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 Ligand has a PDB structure 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
Immuno Process:  Immune regulation
Immuno Process:  Cellular signalling
Immuno Process:  Inflammation
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

Show »

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

There should be a chart of expression data here, you may need to enable JavaScript!
Functional Assays 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

Show »

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Adrb1tm1Bkk|Adrb2tm1Bkk|Adrb3tm1Lowl Adrb1tm1Bkk/Adrb1tm1Bkk,Adrb2tm1Bkk/Adrb2tm1Bkk,Adrb3tm1Lowl/Adrb3tm1Lowl
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N		 MGI:87937  MGI:87938  MGI:87939  MP:0001777 abnormal body temperature regulation PMID: 12161655 
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

Show »

1. Abraham G, Kneuer C, Ehrhardt C, Honscha W, Ungemach FR. (2004) Expression of functional beta2-adrenergic receptors in the lung epithelial cell lines 16HBE14o(-), Calu-3 and A549. Biochim Biophys Acta, 1691 (2-3): 169-79. [PMID:15110997]

2. Alikhani V, Beer D, Bentley D, Bruce I, Cuenoud BM, Fairhurst RA, Gedeck P, Haberthuer S, Hayden C, Janus D et al.. (2004) Long-chain formoterol analogues: an investigation into the effect of increasing amino-substituent chain length on the beta2-adrenoceptor activity. Bioorg Med Chem Lett, 14 (18): 4705-10. [PMID:15324892]

3. Allen JM, Baetge EE, Abrass IB, Palmiter RD. (1988) Isoproterenol response following transfection of the mouse beta 2-adrenergic receptor gene into Y1 cells. EMBO J, 7 (1): 133-8. [PMID:2834198]

4. André C, Erraji L, Gaston J, Grimber G, Briand P, Guillet JG. (1996) Transgenic mice carrying the human beta 2-adrenergic receptor gene with its own promoter overexpress beta 2-adrenergic receptors in liver. Eur J Biochem, 241 (2): 417-24. [PMID:8917438]

5. Angers S, Salahpour A, Joly E, Hilairet S, Chelsky D, Dennis M, Bouvier M. (2000) Detection of beta 2-adrenergic receptor dimerization in living cells using bioluminescence resonance energy transfer (BRET). Proc Natl Acad Sci USA, 97 (7): 3684-9. [PMID:10725388]

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

7. Aristotelous T, Ahn S, Shukla AK, Gawron S, Sassano MF, Kahsai AW, Wingler LM, Zhu X, Tripathi-Shukla P, Huang XP et al.. (2013) Discovery of β2 Adrenergic Receptor Ligands Using Biosensor Fragment Screening of Tagged Wild-Type Receptor. ACS Med Chem Lett, 4 (10): 1005-1010. [PMID:24454993]

8. Auerbach SS, DrugMatrix® and ToxFX® Coordinator National Toxicology Program. National Toxicology Program: Dept of Health and Human Services. Accessed on 02/05/2014. Modified on 02/05/2014. DrugMatrix, https://ntp.niehs.nih.gov/drugmatrix/index.html

9. Baerwald C, Graefe C, Muhl C, Von Wichert P, Krause A. (1992) Beta 2-adrenergic receptors on peripheral blood mononuclear cells in patients with rheumatic diseases. Eur J Clin Invest, 22 Suppl 1: 42-6. [PMID:1333966]

10. Baker JG. (2005) The selectivity of beta-adrenoceptor antagonists at the human beta1, beta2 and beta3 adrenoceptors. Br J Pharmacol, 144 (3): 317-22. [PMID:15655528]

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

12. Baker JG, Hall IP, Hill SJ. (2002) Pharmacological characterization of CGP 12177 at the human beta(2)-adrenoceptor. Br J Pharmacol, 137 (3): 400-8. [PMID:12237261]

13. Baker JG, Hall IP, Hill SJ. (2003) Influence of agonist efficacy and receptor phosphorylation on antagonist affinity measurements: differences between second messenger and reporter gene responses. Mol Pharmacol, 64 (3): 679-88. [PMID:12920204]

14. Baker JG, Proudman RG, Hill SJ. (2015) Salmeterol's extreme β2 selectivity is due to residues in both extracellular loops and transmembrane domains. Mol Pharmacol, 87 (1): 103-20. [PMID:25324048]

15. Barki-Harrington L, Luttrell LM, Rockman HA. (2003) Dual inhibition of beta-adrenergic and angiotensin II receptors by a single antagonist: a functional role for receptor-receptor interaction in vivo. Circulation, 108 (13): 1611-8. [PMID:12963634]

16. Battram C, Charlton SJ, Cuenoud B, Dowling MR, Fairhurst RA, Farr D, Fozard JR, Leighton-Davies JR, Lewis CA, McEvoy L et al.. (2006) In vitro and in vivo pharmacological characterization of 5-[(R)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-1H-quinolin-2-one (indacaterol), a novel inhaled beta(2) adrenoceptor agonist with a 24-h duration of action. J Pharmacol Exp Ther, 317 (2): 762-70. [PMID:16434564]

17. Beattie D, Beer D, Bradley ME, Bruce I, Charlton SJ, Cuenoud BM, Fairhurst RA, Farr D, Fozard JR, Janus D et al.. (2012) An investigation into the structure-activity relationships associated with the systematic modification of the β(2)-adrenoceptor agonist indacaterol. Bioorg Med Chem Lett, 22 (19): 6280-5. [PMID:22932315]

18. Berthouze M, Ayoub M, Russo O, Rivail L, Sicsic S, Fischmeister R, Berque-Bestel I, Jockers R, Lezoualc'h F. (2005) Constitutive dimerization of human serotonin 5-HT4 receptors in living cells. FEBS Lett, 579 (14): 2973-80. [PMID:15896782]

19. Bokoch MP, Zou Y, Rasmussen SG, Liu CW, Nygaard R, Rosenbaum DM, Fung JJ, Choi HJ, Thian FS, Kobilka TS et al.. (2010) Ligand-specific regulation of the extracellular surface of a G-protein-coupled receptor. Nature, 463 (7277): 108-12. [PMID:20054398]

20. Bouyssou T, Casarosa P, Naline E, Pestel S, Konetzki I, Devillier P, Schnapp A. (2010) Pharmacological characterization of olodaterol, a novel inhaled beta2-adrenoceptor agonist exerting a 24-hour-long duration of action in preclinical models. J Pharmacol Exp Ther, 334 (1): 53-62. [PMID:20371707]

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

22. Brown DA, Dunn PM. (1983) Depolarization of rat isolated superior cervical ganglia mediated by beta 2-adrenoceptors. Br J Pharmacol, 79 (2): 429-39. [PMID:6140042]

23. Callaerts-Vegh Z, Evans KL, Dudekula N, Cuba D, Knoll BJ, Callaerts PF, Giles H, Shardonofsky FR, Bond RA. (2004) Effects of acute and chronic administration of beta-adrenoceptor ligands on airway function in a murine model of asthma. Proc Natl Acad Sci USA, 101 (14): 4948-53. [PMID:15069206]

24. Candelore MR, Deng L, Tota L, Guan XM, Amend A, Liu Y, Newbold R, Cascieri MA, Weber AE. (1999) Potent and selective human beta(3)-adrenergic receptor antagonists. J Pharmacol Exp Ther, 290 (2): 649-55. [PMID:10411574]

25. Carzaniga L, Linney ID, Rizzi A, Delcanale M, Schmidt W, Knight CK, Pastore F, Miglietta D, Carnini C, Cesari N et al.. (2022) Discovery of Clinical Candidate CHF-6366: A Novel Super-soft Dual Pharmacology Muscarinic Antagonist and β2 Agonist (MABA) for the Inhaled Treatment of Respiratory Diseases. J Med Chem, 65 (15): 10233-10250. [PMID:35901125]

26. Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK et al.. (2007) High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science, 318 (5854): 1258-65. [PMID:17962520]

27. Chruscinski AJ, Rohrer DK, Schauble E, Desai KH, Bernstein D, Kobilka BK. (1999) Targeted disruption of the beta2 adrenergic receptor gene. J Biol Chem, 274 (24): 16694-700. [PMID:10358008]

28. Cockcroft JR, Gazis AG, Cross DJ, Wheatley A, Dewar J, Hall IP, Noon JP. (2000) Beta(2)-adrenoceptor polymorphism determines vascular reactivity in humans. Hypertension, 36 (3): 371-5. [PMID:10988267]

29. De Pascali F, Ippolito M, Wolfe E, Komolov KE, Hopfinger N, Lemenze D, Kim N, Armen RS, An SS, Scott CP et al.. (2022) β2 -Adrenoceptor agonist profiling reveals biased signalling phenotypes for the β2 -adrenoceptor with possible implications for the treatment of asthma. Br J Pharmacol, 179 (19): 4692-4708. [PMID:35732075]

30. Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES. (2000) The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev, 52 (4): 595-638. [PMID:11121511]

31. Frazier EP, Michel-Reher MB, van Loenen P, Sand C, Schneider T, Peters SL, Michel MC. (2011) Lack of evidence that nebivolol is a β₃-adrenoceptor agonist. Eur J Pharmacol, 654 (1): 86-91. [PMID:21172342]

32. Frielle T, Daniel KW, Caron MG, Lefkowitz RJ. (1988) Structural basis of beta-adrenergic receptor subtype specificity studied with chimeric beta 1/beta 2-adrenergic receptors. Proc Natl Acad Sci USA, 85 (24): 9494-8. [PMID:2849109]

33. Garovic VD, Joyner MJ, Dietz NM, Boerwinkle E, Turner ST. (2003) Beta(2)-adrenergic receptor polymorphism and nitric oxide-dependent forearm blood flow responses to isoproterenol in humans. J Physiol (Lond.), 546 (Pt 2): 583-9. [PMID:12527744]

34. Gocayne J, Robinson DA, FitzGerald MG, Chung FZ, Kerlavage AR, Lentes KU, Lai J, Wang CD, Fraser CM, Venter JC. (1987) Primary structure of rat cardiac beta-adrenergic and muscarinic cholinergic receptors obtained by automated DNA sequence analysis: further evidence for a multigene family. Proc Natl Acad Sci USA, 84 (23): 8296-300. [PMID:2825184]

35. Haack KK, Tougas MR, Jones KT, El-Dahr SS, Radhakrishna H, McCarty NA. (2010) A novel bioassay for detecting GPCR heterodimerization: transactivation of beta 2 adrenergic receptor by bradykinin receptor. J Biomol Screen, 15 (3): 251-60. [PMID:20150590]

36. Hague C, Uberti MA, Chen Z, Bush CF, Jones SV, Ressler KJ, Hall RA, Minneman KP. (2004) Olfactory receptor surface expression is driven by association with the beta2-adrenergic receptor. Proc Natl Acad Sci USA, 101 (37): 13672-6. [PMID:15347813]

37. Hanson MA, Cherezov V, Griffith MT, Roth CB, Jaakola VP, Chien EY, Velasquez J, Kuhn P, Stevens RC. (2008) A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor. Structure, 16 (6): 897-905. [PMID:18547522]

38. Hebert TE, Moffett S, Morello JP, Loisel TP, Bichet DG, Barret C, Bouvier M. (1996) A peptide derived from a beta2-adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation. J Biol Chem, 271 (27): 16384-92. [PMID:8663163]

39. Heubach JF, Trebess I, Wettwer E, Himmel HM, Michel MC, Kaumann AJ, Koch WJ, Harding SE, Ravens U. (1999) L-type calcium current and contractility in ventricular myocytes from mice overexpressing the cardiac beta 2-adrenoceptor. Cardiovasc Res, 42 (1): 173-82. [PMID:10435008]

40. Hillman KL, Doze VA, Porter JE. (2005) Functional characterization of the beta-adrenergic receptor subtypes expressed by CA1 pyramidal cells in the rat hippocampus. J Pharmacol Exp Ther, 314 (2): 561-7. [PMID:15908513]

41. Hoenke C, Bouyssou T, Tautermann CS, Rudolf K, Schnapp A, Konetzki I. (2009) Use of 5-hydroxy-4H-benzo[1,4]oxazin-3-ones as beta2-adrenoceptor agonists. Bioorg Med Chem Lett, 19 (23): 6640-4. [PMID:19875286]

42. Hoffmann C, Leitz MR, Oberdorf-Maass S, Lohse MJ, Klotz KN. (2004) Comparative pharmacology of human beta-adrenergic receptor subtypes--characterization of stably transfected receptors in CHO cells. Naunyn Schmiedebergs Arch Pharmacol, 369 (2): 151-9. [PMID:14730417]

43. Hoit BD, Suresh DP, Craft L, Walsh RA, Liggett SB. (2000) beta2-adrenergic receptor polymorphisms at amino acid 16 differentially influence agonist-stimulated blood pressure and peripheral blood flow in normal individuals. Am Heart J, 139 (3): 537-42. [PMID:10689270]

44. Hudson BD, Hébert TE, Kelly ME. (2010) Physical and functional interaction between CB1 cannabinoid receptors and beta2-adrenoceptors. Br J Pharmacol, 160 (3): 627-42. [PMID:20590567]

45. Isogaya M, Sugimoto Y, Tanimura R, Tanaka R, Kikkawa H, Nagao T, Kurose H. (1999) Binding pockets of the beta(1)- and beta(2)-adrenergic receptors for subtype-selective agonists. Mol Pharmacol, 56 (5): 875-85. [PMID:10531390]

46. Izeboud CA, Vermeulen RM, Zwart A, Voss HP, van Miert AS, Witkamp RF. (2000) Stereoselectivity at the beta2-adrenoceptor on macrophages is a major determinant of the anti-inflammatory effects of beta2-agonists. Naunyn Schmiedebergs Arch Pharmacol, 362 (2): 184-9. [PMID:10961382]

47. January B, Seibold A, Whaley B, Hipkin RW, Lin D, Schonbrunn A, Barber R, Clark RB. (1997) beta2-adrenergic receptor desensitization, internalization, and phosphorylation in response to full and partial agonists. J Biol Chem, 272 (38): 23871-9. [PMID:9295336]

48. Joiner ML, Lisé MF, Yuen EY, Kam AY, Zhang M, Hall DD, Malik ZA, Qian H, Chen Y, Ulrich JD et al.. (2010) Assembly of a beta2-adrenergic receptor--GluR1 signalling complex for localized cAMP signalling. EMBO J, 29 (2): 482-95. [PMID:19942860]

49. Jordan BA, Trapaidze N, Gomes I, Nivarthi R, Devi LA. (2001) Oligomerization of opioid receptors with beta 2-adrenergic receptors: a role in trafficking and mitogen-activated protein kinase activation. Proc Natl Acad Sci USA, 98 (1): 343-8. [PMID:11134510]

50. Kern C, Meyer T, Droux S, Schollmeyer D, Miculka C. (2009) Synthesis and pharmacological characterization of beta2-adrenergic agonist enantiomers: zilpaterol. J Med Chem, 52 (6): 1773-7. [PMID:19245211]

51. Kobilka BK, Dixon RA, Frielle T, Dohlman HG, Bolanowski MA, Sigal IS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ. (1987) cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor. Proc Natl Acad Sci USA, 84 (1): 46-50. [PMID:3025863]

52. Krushinski Jr JH, Schaus JM, Thompson DC, Calligaro DO, Nelson DL, Luecke SH, Wainscott DB, Wong DT. (2007) Indoloxypropanolamine analogues as 5-HT(1A) receptor antagonists. Bioorg Med Chem Lett, 17 (20): 5600-4. [PMID:17804228]

53. Kuravi S, Lan TH, Barik A, Lambert NA. (2010) Third-party bioluminescence resonance energy transfer indicates constitutive association of membrane proteins: application to class a g-protein-coupled receptors and g-proteins. Biophys J, 98 (10): 2391-9. [PMID:20483349]

54. Lakhlani PP, Amenta F, Napoleone P, Felici L, Eikenburg DC. (1994) Pharmacological characterization and anatomical localization of prejunctional beta-adrenoceptors in the rat kidney. Br J Pharmacol, 111: 1296-1308. [PMID:8032617]

55. LaRocca TJ, Schwarzkopf M, Altman P, Zhang S, Gupta A, Gomes I, Alvin Z, Champion HC, Haddad G, Hajjar RJ et al.. (2010) β2-Adrenergic receptor signaling in the cardiac myocyte is modulated by interactions with CXCR4. J Cardiovasc Pharmacol, 56 (5): 548-59. [PMID:20729750]

56. Lavoie C, Hébert TE. (2003) Pharmacological characterization of putative beta1-beta2-adrenergic receptor heterodimers. Can J Physiol Pharmacol, 81 (2): 186-95. [PMID:12710533]

57. Lavoie C, Mercier JF, Salahpour A, Umapathy D, Breit A, Villeneuve LR, Zhu WZ, Xiao RP, Lakatta EG, Bouvier M et al.. (2002) Beta 1/beta 2-adrenergic receptor heterodimerization regulates beta 2-adrenergic receptor internalization and ERK signaling efficacy. J Biol Chem, 277 (38): 35402-10. [PMID:12140284]

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

59. Li F, De Godoy M, Rattan S. (2004) Role of adenylate and guanylate cyclases in beta1-, beta2-, and beta3-adrenoceptor-mediated relaxation of internal anal sphincter smooth muscle. J Pharmacol Exp Ther, 308 (3): 1111-20. [PMID:14711933]

60. Liapakis G, Chan WC, Papadokostaki M, Javitch JA. (2004) Synergistic contributions of the functional groups of epinephrine to its affinity and efficacy at the beta2 adrenergic receptor. Mol Pharmacol, 65 (5): 1181-90. [PMID:15102946]

61. Liu X, Kaindl J, Korczynska M, Stößel A, Dengler D, Stanek M, Hübner H, Clark MJ, Mahoney J, Matt RA et al.. (2020) An allosteric modulator binds to a conformational hub in the β2 adrenergic receptor. Nat Chem Biol, 16 (7): 749-755. [PMID:32483378]

62. Liu YL, Nwosu UC, Rice PJ. (1998) Relaxation of isolated human myometrial muscle by beta2-adrenergic receptors but not beta1-adrenergic receptors. Am J Obstet Gynecol, 179 (4): 895-8. [PMID:9790366]

63. Louis SN, Nero TL, Iakovidis D, Jackman GP, Louis WJ. (1999) LK 204-545, a highly selective beta1-adrenoceptor antagonist at human beta-adrenoceptors. Eur J Pharmacol, 367 (2-3): 431-5. [PMID:10079020]

64. Maudsley S, Pierce KL, Zamah AM, Miller WE, Ahn S, Daaka Y, Lefkowitz RJ, Luttrell LM. (2000) The beta(2)-adrenergic receptor mediates extracellular signal-regulated kinase activation via assembly of a multi-receptor complex with the epidermal growth factor receptor. J Biol Chem, 275 (13): 9572-80. [PMID:10734107]

65. McGraw DW, Forbes SL, Kramer LA, Witte DP, Fortner CN, Paul RJ, Liggett SB. (1999) Transgenic overexpression of beta(2)-adrenergic receptors in airway smooth muscle alters myocyte function and ablates bronchial hyperreactivity. J Biol Chem, 274 (45): 32241-7. [PMID:10542262]

66. McGraw DW, Mihlbachler KA, Schwarb MR, Rahman FF, Small KM, Almoosa KF, Liggett SB. (2006) Airway smooth muscle prostaglandin-EP1 receptors directly modulate beta2-adrenergic receptors within a unique heterodimeric complex. J Clin Invest, 116 (5): 1400-9. [PMID:16670773]

67. McVey M, Ramsay D, Kellett E, Rees S, Wilson S, Pope AJ, Milligan G. (2001) Monitoring receptor oligomerization using time-resolved fluorescence resonance energy transfer and bioluminescence resonance energy transfer. The human delta -opioid receptor displays constitutive oligomerization at the cell surface, which is not regulated by receptor occupancy. J Biol Chem, 276 (17): 14092-9. [PMID:11278447]

68. Mercier JF, Salahpour A, Angers S, Breit A, Bouvier M. (2002) Quantitative assessment of beta 1- and beta 2-adrenergic receptor homo- and heterodimerization by bioluminescence resonance energy transfer. J Biol Chem, 277 (47): 44925-31. [PMID:12244098]

69. Minneman KP, Hegstrand LR, Molinoff PB. (1979) The pharmacological specificity of beta-1 and beta-2 adrenergic receptors in rat heart and lung in vitro. Mol Pharmacol, 16 (1): 21-33. [PMID:39243]

70. Potter DE. (1981) Adrenergic pharmacology of aqueous humor dynamics. Pharmacol Rev, 33 (3): 133-53. [PMID:7323134]

71. Procopiou PA, Barrett VJ, Bevan NJ, Biggadike K, Box PC, Butchers PR, Coe DM, Conroy R, Emmons A, Ford AJ et al.. (2010) Synthesis and structure-activity relationships of long-acting beta2 adrenergic receptor agonists incorporating metabolic inactivation: an antedrug approach. J Med Chem, 53 (11): 4522-30. [PMID:20462258]

72. Pönicke K, Heinroth-Hoffmann I, Brodde OE. (2003) Role of beta 1- and beta 2-adrenoceptors in hypertrophic and apoptotic effects of noradrenaline and adrenaline in adult rat ventricular cardiomyocytes. Naunyn Schmiedebergs Arch Pharmacol, 367 (6): 592-9. [PMID:12750877]

73. Rasmussen SG, Choi HJ, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, Burghammer M, Ratnala VR, Sanishvili R, Fischetti RF et al.. (2007) Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature, 450 (7168): 383-7. [PMID:17952055]

74. Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, Calinski D et al.. (2011) Crystal structure of the β2 adrenergic receptor-Gs protein complex. Nature, 477 (7366): 549-55. [PMID:21772288]

75. Rohrer DK, Chruscinski A, Schauble EH, Bernstein D, Kobilka BK. (1999) Cardiovascular and metabolic alterations in mice lacking both beta1- and beta2-adrenergic receptors. J Biol Chem, 274 (24): 16701-8. [PMID:10358009]

76. Rosenbaum DM, Zhang C, Lyons JA, Holl R, Aragao D, Arlow DH, Rasmussen SG, Choi HJ, Devree BT, Sunahara RK et al.. (2011) Structure and function of an irreversible agonist-β(2) adrenoceptor complex. Nature, 469 (7329): 236-40. [PMID:21228876]

77. Sabio M, Jones K, Topiol S. (2008) Use of the X-ray structure of the beta2-adrenergic receptor for drug discovery. Part 2: Identification of active compounds. Bioorg Med Chem Lett, 18 (20): 5391-5. [PMID:18829308]

78. Sato Y, Kurose H, Isogaya M, Nagao T. (1996) Molecular characterization of pharmacological properties of T-0509 for beta-adrenoceptors. Eur J Pharmacol, 315 (3): 363-7. [PMID:8982677]

79. Seifert R, Lee TW, Lam VT, Kobilka BK. (1998) Reconstitution of beta2-adrenoceptor-GTP-binding-protein interaction in Sf9 cells--high coupling efficiency in a beta2-adrenoceptor-G(s alpha) fusion protein. Eur J Biochem, 255 (2): 369-82. [PMID:9716378]

80. Sharif NA, Xu SX, Crider JY, McLaughlin M, Davis TL. (2001) Levobetaxolol (Betaxon) and other beta-adrenergic antagonists: preclinical pharmacology, IOP-lowering activity and sites of action in human eyes. J Ocul Pharmacol Ther, 17 (4): 305-17. [PMID:11572462]

81. Soriano-Ursúa MA, McNaught-Flores DA, Nieto-Alamilla G, Segura-Cabrera A, Correa-Basurto J, Arias-Montaño JA, Trujillo-Ferrara JG. (2012) Cell-based and in-silico studies on the high intrinsic activity of two boron-containing salbutamol derivatives at the human β₂-adrenoceptor. Bioorg Med Chem, 20 (2): 933-41. [PMID:22182578]

82. Soriano-Ursúa MA, Valencia-Hernández I, Arellano-Mendoza MG, Correa-Basurto J, Trujillo-Ferrara JG. (2009) Synthesis, pharmacological and in silico evaluation of 1-(4-di-hydroxy-3,5-dioxa-4-borabicyclo[4.4.0]deca-7,9,11-trien-9-yl)-2-(tert-butylamino)ethanol, a compound designed to act as a beta2 adrenoceptor agonist. Eur J Med Chem, 44 (7): 2840-6. [PMID:19168263]

83. Stiles GL, Caron MG, Lefkowitz RJ. (1984) Beta-adrenergic receptors: biochemical mechanisms of physiological regulation. Physiol Rev, 64 (2): 661-743. [PMID:6143332]

84. Swaminath G, Lee TW, Kobilka B. (2003) Identification of an allosteric binding site for Zn2+ on the beta2 adrenergic receptor. J Biol Chem, 278 (1): 352-6. [PMID:12409304]

85. Swaminath G, Steenhuis J, Kobilka B, Lee TW. (2002) Allosteric modulation of beta2-adrenergic receptor by Zn(2+). Mol Pharmacol, 61 (1): 65-72. [PMID:11752207]

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

87. Tsuchihashi H, Nakashima Y, Kinami J, Nagatomo T. (1990) Characteristics of 125I-iodocyanopindolol binding to beta-adrenergic and serotonin-1B receptors of rat brain: selectivity of beta-adrenergic agents. Jpn J Pharmacol, 52 (2): 195-200. [PMID:1968985]

88. Turki J, Lorenz JN, Green SA, Donnelly ET, Jacinto M, Liggett SB. (1996) Myocardial signaling defects and impaired cardiac function of a human beta 2-adrenergic receptor polymorphism expressed in transgenic mice. Proc Natl Acad Sci USA, 93 (19): 10483-8. [PMID:8816827]

89. Turki J, Pak J, Green SA, Martin RJ, Liggett SB. (1995) Genetic polymorphisms of the beta 2-adrenergic receptor in nocturnal and nonnocturnal asthma. Evidence that Gly16 correlates with the nocturnal phenotype. J Clin Invest, 95 (4): 1635-41. [PMID:7706471]

90. Uberti MA, Hague C, Oller H, Minneman KP, Hall RA. (2005) Heterodimerization with beta2-adrenergic receptors promotes surface expression and functional activity of alpha1D-adrenergic receptors. J Pharmacol Exp Ther, 313 (1): 16-23. [PMID:15615865]

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

92. Wacker D, Fenalti G, Brown MA, Katritch V, Abagyan R, Cherezov V, Stevens RC. (2010) Conserved binding mode of human beta2 adrenergic receptor inverse agonists and antagonist revealed by X-ray crystallography. J Am Chem Soc, 132 (33): 11443-5. [PMID:20669948]

93. Wenzel-Seifert K, Liu HY, Seifert R. (2002) Similarities and differences in the coupling of human beta1- and beta2-adrenoceptors to Gs(alpha) splice variants. Biochem Pharmacol, 64 (1): 9-20. [PMID:12106601]

94. Wrzal PK, Devost D, Pétrin D, Goupil E, Iorio-Morin C, Laporte SA, Zingg HH, Hébert TE. (2012) Allosteric interactions between the oxytocin receptor and the β2-adrenergic receptor in the modulation of ERK1/2 activation are mediated by heterodimerization. Cell Signal, 24 (1): 342-50. [PMID:21963428]

95. Wrzal PK, Goupil E, Laporte SA, Hébert TE, Zingg HH. (2012) Functional interactions between the oxytocin receptor and the β2-adrenergic receptor: implications for ERK1/2 activation in human myometrial cells. Cell Signal, 24 (1): 333-41. [PMID:21964067]

96. Yatani A, Tajima Y, Green SA. (1999) Coupling of beta-adrenergic receptors to cardiac L-type Ca2+ channels: preferential coupling of the beta1 versus beta2 receptor subtype and evidence for PKA-independent activation of the channel. Cell Signal, 11 (5): 337-42. [PMID:10376806]

97. Zhu WZ, Chakir K, Zhang S, Yang D, Lavoie C, Bouvier M, Hébert TE, Lakatta EG, Cheng H, Xiao RP. (2005) Heterodimerization of beta1- and beta2-adrenergic receptor subtypes optimizes beta-adrenergic modulation of cardiac contractility. Circ Res, 97 (3): 244-51. [PMID:16002745]

Contributors

Show »

How to cite this page