β<sub>2</sub>-adrenoceptor | Adrenoceptors | IUPHAR Guide to IMMUNOPHARMACOLOGY

β₂-adrenoceptor

Immunopharmacology Ligand Target has curated data in GtoImmuPdb

Target id: 29

Nomenclature: β₂-adrenoceptor

Gene and Protein Information
Previous and Unofficial Names
Database Links
Selected 3D Structures
Associated Proteins
Natural/Endogenous Ligands
Rank order lists
Agonists
Antagonists
Allosteric Modulators
Immunopharmacology Comments
Immuno Cell Type Associations
Immuno Process Associations
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
Biologically Significant Variants
General Comments
References
Contributors
How to cite this page

Gene and Protein Information
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
ADRB2R \| ADRBR \| B2AR \| beta-2 adrenergic receptor \| beta-2 adrenoreceptor \| Adrb-2 \| beta 2-AR \| Gpcr7 \| adrenoceptor beta 2, surface \| adrenergic receptor

Previous and Unofficial Names

Database Links
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

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

Description:	Crystal structure of the β₂ adrenergic receptor-G_s protein complex
PDB Id:	3SN6
Resolution:	3.2Å
Species:	None
References:	126

Description:	Cholesterol bound form of human β₂-adrenergic receptor
PDB Id:	3D4S
Ligand:	cholesterol
Resolution:	2.8Å
Species:	Human
References:	66

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

Description:	Crystal structure of the human β₂-adrenoceptor
PDB Id:	2R4S
Resolution:	3.4Å
Species:	Human
References:	125

Description:	Crystal structure of a methylated β₂-Adrenergic Receptor-Fab complex
PDB Id:	3KJ6
Resolution:	3.4Å
Species:	Human
References:	27

Description:	Crystal structure of the human β₂-adrenoceptor
PDB Id:	2R4R
Resolution:	3.4Å
Species:	Human
References:	125

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

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

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

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

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

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

Interacting Proteins
Name	Effect	References
β₂-adrenoceptor		6,29,68,92,113
β₁-adrenoceptor		95-96,113,165
β₃-adrenoceptor		29
α_1D-adrenoceptor		151
α_2A-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
(-)-adrenaline
(-)-noradrenaline
Zn²⁺
Comments: Adrenaline exhibits greater potency than noradrenaline

Potency order of endogenous ligands (Human)
(-)-adrenaline > (-)-noradrenaline

Potency order of endogenous ligands (Human)

(-)-adrenaline > (-)-noradrenaline

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Agonists

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Ligand		Sp.	Action	Value	Parameter	Reference
CHF-6366		Hs	Agonist	11.4	pK_d	37
⤷	pK_d 11.4 (K_d 4x10^-12 M) [37] Description: Binding to human cloned β₂ receptor using 125I-cyanopindolol as tracer
[³H]CGP12177		Hs	Partial agonist	9.8	pK_d	14
⤷	pK_d 9.8 (K_d 1.44x10^-10 M) [14] Description: Binding to human &beta₂-adrenoceptor expressed in CHO-K1 cells, in a whole cell binding assay.
orciprenaline		Hs	Agonist	5.3	pK_d	138
⤷	pK_d 5.3 (K_d 4.81x10^-6 M) [138]
pindolol		Hs	Partial agonist	9.4	pK_i	91
⤷	pK_i 9.4 (K_i 4x10^-10 M) [91]
salmeterol		Hs	Partial agonist	6.8 – 9.3	pK_i	13,17,45
⤷	pK_i 6.8 – 9.3 [13,17,45]
zinterol		Hs	Agonist	8.0	pK_i	13
⤷	pK_i 8.0 [13]
clenbuterol		Hs	Full agonist	7.4 – 7.9	pK_i	13,17,89
⤷	pK_i 7.4 – 7.9 [13,17,89]
indacaterol		Hs	Agonist	7.4 – 7.8	pK_i	20-21
⤷	pK_i 7.4 – 7.8 [20-21]
BRL35135		Hs	Partial agonist	7.4	pK_i	13
⤷	pK_i 7.4 [13]
procaterol		Hs	Agonist	7.1	pK_i	13
⤷	pK_i 7.1 [13]
ractopamine		Hs	Partial agonist	6.6 – 6.9	pK_i	13,45,81
⤷	pK_i 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		Hs	Full agonist	6.4 – 6.6	pK_i	13-14,133
⤷	pK_i 6.4 – 6.6 [13-14,133]
BRL 37344		Hs	Partial agonist	6.5	pK_i	13
⤷	pK_i 6.5 [13]
fenoterol		Hs	Agonist	5.5 – 7.0	pK_i	9,13,17,45
⤷	pK_i 5.5 – 7.0 [9,13,17,45]
(-)-adrenaline		Hs	Full agonist	6.0 – 6.2	pK_i	13,53,73,83
⤷	pK_i 6.0 – 6.2 [13,53,73,83]
salbutamol		Hs	Partial agonist	5.3 – 6.1	pK_i	12-13,17,45,81,137
⤷	pK_i 5.3 – 6.1 [12-13,17,45,81,137]
ephedrine		Hs	Partial agonist	5.6	pK_i	83
⤷	pK_i 5.6 [83]
terbutaline		Hs	Partial agonist	5.5 – 5.6	pK_i	12-13
⤷	pK_i 5.5 – 5.6 [12-13]
noradrenaline		Hs	Full agonist	5.4	pK_i	100
⤷	pK_i 5.4 [100]
(-)-noradrenaline		Hs	Agonist	4.6 – 5.4	pK_i	13,53,73
⤷	pK_i 4.6 – 5.4 [13,53,73]
olodaterol		Hs	Agonist	10.0	pEC₅₀	28
⤷	pEC₅₀ 10.0 (IC₅₀ 1x10^-10 M) [28]
BI-167107		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		Hs	Partial agonist	9.2 – 9.9	pEC₅₀	13,20
⤷	pEC₅₀ 9.2 – 9.9 [13,20]
zinterol		Hs	Agonist	9.5	pEC₅₀	13
⤷	pEC₅₀ 9.5 [13]
vilanterol		Hs	Agonist	9.4	pEC₅₀	122
⤷	pEC₅₀ 9.4 (EC₅₀ 3.98x10^-10 M) [122]
clenbuterol		Hs	Agonist	9.2	pEC₅₀	13
⤷	pEC₅₀ 9.2 [13]
formoterol		Hs	Agonist	7.8 – 10.1	pEC₅₀	3,13,17,20,102
⤷	pEC₅₀ 7.8 – 10.1 [3,13,17,20,102]
BRL35135		Hs	Partial agonist	8.7	pEC₅₀	13
⤷	pEC₅₀ 8.7 [13]
procaterol		Hs	Agonist	8.4	pEC₅₀	13
⤷	pEC₅₀ 8.4 [13]
isoprenaline		Hs	Full agonist	8.2	pEC₅₀	13-14
⤷	pEC₅₀ 8.2 [13-14]
indacaterol		Hs	Agonist	8.1	pEC₅₀	20
⤷	pEC₅₀ 8.1 [20]
(-)-adrenaline		Hs	Full agonist	7.9	pEC₅₀	13
⤷	pEC₅₀ 7.9 [13]
ractopamine		Hs	Partial agonist	7.6 – 7.8	pEC₅₀	13,45
⤷	pEC₅₀ 7.6 – 7.8 [13,45]
fenoterol		Hs	Agonist	6.1 – 8.9	pEC₅₀	13,45
⤷	pEC₅₀ 6.1 – 8.9 [13,45]
terbutaline		Hs	Partial agonist	7.3	pEC₅₀	13
⤷	pEC₅₀ 7.3 [13]
salbutamol		Hs	Partial agonist	6.3 – 7.7	pEC₅₀	13,45
⤷	pEC₅₀ 6.3 – 7.7 [13,45]
BRL 37344		Hs	Partial agonist	6.9	pEC₅₀	13
⤷	pEC₅₀ 6.9 [13]
(-)-noradrenaline		Hs	Agonist	6.4	pEC₅₀	13
⤷	pEC₅₀ 6.4 [13]
solabegron		Hs	Agonist	5.9	pEC₅₀	152
⤷	pEC₅₀ 5.9 [152]
mirabegron		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		Rn	Agonist	5.0	pEC₅₀	46
⤷	pEC₅₀ 5.0 [46]
abediterol		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		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. pK_i 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		Rn	Antagonist	6.4	pK_B	71
⤷	pK_B 6.4 (K_B 3.55x10^-7 M) [71]
butoxamine		Hs	Antagonist	6.2 – 6.5	pK_B	13,31,148
⤷	pK_B 6.2 – 6.5 [13,31,148]
[¹²⁵I]ICYP		Hs	Antagonist	11.1 – 11.4	pK_d	107,133,144
⤷	pK_d 11.1 – 11.4 (K_d 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		Hs	Inverse agonist	10.4	pK_d	132
⤷	pK_d 10.4 [132]
[³H]dihydroalprenolol		Hs	Antagonist	10.1	pK_d	144
⤷	pK_d 10.1 [144]
[³H]CGP12177		Hs	Partial agonist	9.8	pK_d	14
⤷	pK_d 9.8 [14]
carazolol		Hs	Antagonist	9.9 – 10.5	pK_i	13,130
⤷	pK_i 9.9 – 10.5 [13,130]
timolol		Hs	Antagonist	9.7	pK_i	12
⤷	pK_i 9.7 [12]
carvedilol		Hs	Antagonist	9.4 – 9.9	pK_i	12,35
⤷	pK_i 9.4 – 9.9 [12,35]
pindolol		Hs	Antagonist	9.4	pK_i	91
⤷	pK_i 9.4 [91]
CGP 12177		Hs	Antagonist	9.4	pK_i	12,14,107
⤷	pK_i 9.4 [12,14,107]
ICI 118551		Hs	Inverse agonist	9.2 – 9.5	pK_i	12,16,107
⤷	pK_i 9.2 – 9.5 [12,16,107]
propranolol		Hs	Antagonist	9.1 – 9.5	pK_i	12,16,81,107
⤷	pK_i 9.1 – 9.5 [12,16,81,107]
bunolol		Hs	Antagonist	9.3	pK_i	10
⤷	pK_i 9.3 (K_i 5.5x10^-10 M) [10]
bupranolol		Hs	Antagonist	8.3 – 9.9	pK_i	12,35,107
⤷	pK_i 8.3 – 9.9 [12,35,107]
alprenolol		Hs	Partial agonist	9.0	pK_i	12
⤷	pK_i 9.0 [12]
SR59230A		Hs	Antagonist	8.5 – 9.3	pK_i	12,35
⤷	pK_i 8.5 – 9.3 [12,35]
labetalol		Hs	Partial agonist	8.0	pK_i	10,12
⤷	pK_i 8.0 (K_i 1.1x10^-8 M) [10,12]
nebivolol		Hs	Antagonist	7.9 – 8.0	pK_i	13,51
⤷	pK_i 7.9 – 8.0 [13,51] Description: Radioligand binding
nadolol		Hs	Antagonist	7.0 – 8.6	pK_i	12,35
⤷	pK_i 7.0 – 8.6 [12,35]
betaxolol		Hs	Antagonist	7.2 – 8.2	pK_i	13,107,135
⤷	pK_i 7.2 – 8.2 [13,107,135]
NIP		Hs	Antagonist	7.5	pK_i	107
⤷	pK_i 7.5 [107]
propafenone		Hs	Antagonist	7.4	pK_i	10
⤷	pK_i 7.4 (K_i 3.6x10^-8 M) [10]
sotalol		Hs	Antagonist	6.5 – 6.9	pK_i	10,12
⤷	pK_i 6.5 – 6.9 [10,12]
metoprolol		Hs	Antagonist	6.3 – 6.9	pK_i	12,107
⤷	pK_i 6.3 – 6.9 [12,107]
butoxamine		Rn	Antagonist	6.3 – 6.5	pK_i	31,148
⤷	pK_i 6.3 – 6.5 (K_i 4.68x10^-7 – 3.09x10^-7 M) [31,148]
cicloprolol		Hs	Antagonist	6.2	pK_i	107
⤷	pK_i 6.2 [107]
NIHP		Hs	Antagonist	6.0	pK_i	107
⤷	pK_i 6.0 [107]
atenolol		Hs	Antagonist	5.6 – 6.0	pK_i	12,107
⤷	pK_i 5.6 – 6.0 [12,107]
LK 204-545		Hs	Antagonist	5.2	pK_i	107
⤷	pK_i 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 G_s 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⁺		Hs	Positive	5.3	pK_i	142-143
⤷	pK_i 5.3 [142-143]
Zn²⁺		Hs	Negative	3.3	pK_i	142-143
⤷	pK_i 3.3 [142-143]
AS408		N/A	-	-	-	104
⤷	[104]
compound 6 [PMID: 29769246]		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].

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]. T_reg cells (CL:0000815): β₂-AR agonist increases T_reg-cell suppressive function associated with decreased IL-2 mRNA levels in responder CD4⁺ T cells and improved T_reg-cell-induced conversion of CD4⁺ Foxp3^- cells into Foxp3⁺ induced T_reg 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:

Immuno Process:

Immuno Process:

Immuno Process:

Primary Transduction Mechanisms
Transducer	Effector/Response
G_s 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
Transducer	Effector/Response
G_i/G_o 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

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

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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

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 G_s, 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, Gα_s or Gα_i.

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

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 G_s 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 G_s/cAMP pathway and the G_i/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

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 G_isignaling 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

Mouse data from MGI

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Allele	Composition & genetic background	Accession	Phenotype Id	Phenotype	Reference
Adrb1^tm1Bkk\|Adrb2^tm1Bkk\|Adrb3^tm1Lowl	Adrb1^tm1Bkk/Adrb1^tm1Bkk,Adrb2^tm1Bkk/Adrb2^tm1Bkk,Adrb3^tm1Lowl/Adrb3^tm1Lowl 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
Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2^tm1Bkk involves: 129S1/Sv * 129X1/SvJ	MGI:87938	MP:0004945	abnormal bone resorption	PMID: 15724149
Adrb2⁺\|Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2⁺ involves: 129S1/Sv * 129X1/SvJ	MGI:87938	MP:0004945	abnormal bone resorption	PMID: 15724149
Adrb1^tm1Bkk\|Adrb2^tm1Bkk\|Adrb3^tm1Lowl	Adrb1^tm1Bkk/Adrb1^tm1Bkk,Adrb2^tm1Bkk/Adrb2^tm1Bkk,Adrb3^tm1Lowl/Adrb3^tm1Lowl 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
Adrb1^tm1Bkk\|Adrb2^tm1Bkk	Adrb1^tm1Bkk/Adrb1^tm1Bkk,Adrb2^tm1Bkk/Adrb2^tm1Bkk involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N	MGI:87937 MGI:87938	MP:0001544	abnormal cardiovascular system physiology	PMID: 10358009
Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2^tm1Bkk FVB.129-Adrb2	MGI:87938	MP:0006319	abnormal epididymal fat pad morphology	PMID: 10358008
Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2^tm1Bkk FVB.129-Adrb2	MGI:87938	MP:0002332	abnormal exercise endurance	PMID: 10358008
Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2^tm1Bkk FVB.129-Adrb2	MGI:87938	MP:0001629	abnormal heart rate	PMID: 10358008
Adrb2^tm1Kry\|Tg(Col1a1-cre)1Kry	Adrb2^tm1Kry/Adrb2^tm1Kry,Tg(Col1a1-cre)1Kry/0 involves: FVB	MGI:3041865 MGI:87938	MP:0003564	abnormal insulin secretion	PMID: 19103808
Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2^tm1Bkk involves: 129S1/Sv * 129X1/SvJ	MGI:87938	MP:0005006	abnormal osteoblast physiology	PMID: 15724149
Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2^tm1Bkk involves: 129S1/Sv * 129X1/SvJ	MGI:87938	MP:0008396	abnormal osteoclast differentiation	PMID: 15724149
Adrb2⁺\|Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2⁺ involves: 129S1/Sv * 129X1/SvJ	MGI:87938	MP:0008396	abnormal osteoclast differentiation	PMID: 15724149
Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2^tm1Bkk involves: 129S1/Sv * 129X1/SvJ	MGI:87938	MP:0004982	abnormal osteoclast morphology	PMID: 15724149
Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2^tm1Bkk involves: 129S1/Sv * 129X1/SvJ	MGI:87938	MP:0001541	abnormal osteoclast physiology	PMID: 15724149
Adrb1^tm1Bkk\|Adrb2^tm1Bkk	Adrb1^tm1Bkk/Adrb1^tm1Bkk,Adrb2^tm1Bkk/Adrb2^tm1Bkk involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N	MGI:87937 MGI:87938	MP:0008872	abnormal physiological response to xenobiotic	PMID: 10358009
Adrb1^tm1Bkk\|Adrb2^tm1Bkk	Adrb1^tm1Bkk/Adrb1^tm1Bkk,Adrb2^tm1Bkk/Adrb2^tm1Bkk 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
Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2^tm1Bkk FVB.129-Adrb2	MGI:87938	MP:0001262	decreased body weight	PMID: 10358008
Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2^tm1Bkk involves: 129S1/Sv * 129X1/SvJ	MGI:87938	MP:0004993	decreased bone resorption	PMID: 15724149
Adrb2⁺\|Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2⁺ involves: 129S1/Sv * 129X1/SvJ	MGI:87938	MP:0004993	decreased bone resorption	PMID: 15724149
Adrb1^tm1Bkk\|Adrb2^tm1Bkk	Adrb1^tm1Bkk/Adrb1^tm1Bkk,Adrb2^tm1Bkk/Adrb2^tm1Bkk involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N	MGI:87937 MGI:87938	MP:0005140	decreased cardiac muscle contractility	PMID: 10358009
Adrb2^tm1Kry\|Tg(Col1a1-cre)1Kry	Adrb2^tm1Kry/Adrb2^tm1Kry,Tg(Col1a1-cre)1Kry/0 involves: FVB	MGI:3041865 MGI:87938	MP:0005560	decreased circulating glucose level	PMID: 19103808
Adrb2⁺\|Adrb2^tm1Kry\|Lep⁺\|Lep^ob\|Tg(Col1a1-cre)1Kry	Adrb2^tm1Kry/Adrb2⁺,Lep^ob/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
Adrb1^tm1Bkk\|Adrb2^tm1Bkk	Adrb1^tm1Bkk/Adrb1^tm1Bkk,Adrb2^tm1Bkk/Adrb2^tm1Bkk involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N	MGI:87937 MGI:87938	MP:0005333	decreased heart rate	PMID: 10358009
Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2^tm1Bkk FVB.129-Adrb2	MGI:87938	MP:0004876	decreased mean systemic arterial blood pressure	PMID: 10358008
Adrb1^tm1Bkk\|Adrb2^tm1Bkk	Adrb1^tm1Bkk/Adrb1^tm1Bkk,Adrb2^tm1Bkk/Adrb2^tm1Bkk involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N	MGI:87937 MGI:87938	MP:0005290	decreased oxygen consumption	PMID: 10358009
Adrb1^tm1Bkk\|Adrb2^tm1Bkk\|Adrb3^tm1Lowl	Adrb1^tm1Bkk/Adrb1^tm1Bkk,Adrb2^tm1Bkk/Adrb2^tm1Bkk,Adrb3^tm1Lowl/Adrb3^tm1Lowl involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N	MGI:87937 MGI:87938 MGI:87939	MP:0005290	decreased oxygen consumption	PMID: 12161655
Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2^tm1Bkk FVB.129-Adrb2	MGI:87938	MP:0010379	decreased respiratory quotient	PMID: 10358008
Adrb1^tm1Bkk\|Adrb2^tm1Bkk\|Adrb3^tm1Lowl	Adrb1^tm1Bkk/Adrb1^tm1Bkk,Adrb2^tm1Bkk/Adrb2^tm1Bkk,Adrb3^tm1Lowl/Adrb3^tm1Lowl involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * DBA/2 * FVB/N	MGI:87937 MGI:87938 MGI:87939	MP:0001260	increased body weight	PMID: 12161655
Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2^tm1Bkk involves: 129S1/Sv * 129X1/SvJ	MGI:87938	MP:0005605	increased bone mass	PMID: 15724149
Adrb2⁺\|Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2⁺ involves: 129S1/Sv * 129X1/SvJ	MGI:87938	MP:0005605	increased bone mass	PMID: 15724149
Adrb1^tm1Bkk\|Adrb2^tm1Bkk\|Adrb3^tm1Lowl	Adrb1^tm1Bkk/Adrb1^tm1Bkk,Adrb2^tm1Bkk/Adrb2^tm1Bkk,Adrb3^tm1Lowl/Adrb3^tm1Lowl 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
Adrb2^tm1Kry\|Tg(Col1a1-cre)1Kry	Adrb2^tm1Kry/Adrb2^tm1Kry,Tg(Col1a1-cre)1Kry/0 involves: FVB	MGI:3041865 MGI:87938	MP:0002079	increased circulating insulin level	PMID: 19103808
Adrb2⁺\|Adrb2^tm1Kry\|Lep⁺\|Lep^ob\|Tg(Col1a1-cre)1Kry	Adrb2^tm1Kry/Adrb2⁺,Lep^ob/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
Adrb1^tm1Bkk\|Adrb2^tm1Bkk\|Adrb3^tm1Lowl	Adrb1^tm1Bkk/Adrb1^tm1Bkk,Adrb2^tm1Bkk/Adrb2^tm1Bkk,Adrb3^tm1Lowl/Adrb3^tm1Lowl 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
Adrb1^tm1Bkk\|Adrb2^tm1Bkk\|Adrb3^tm1Lowl	Adrb1^tm1Bkk/Adrb1^tm1Bkk,Adrb2^tm1Bkk/Adrb2^tm1Bkk,Adrb3^tm1Lowl/Adrb3^tm1Lowl 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
Adrb2^tm1Bkk	Adrb2^tm1Bkk/Adrb2^tm1Bkk FVB.129-Adrb2	MGI:87938	MP:0002842	increased systemic arterial blood pressure	PMID: 10358008
Adrb1^tm1Bkk\|Adrb2^tm1Bkk\|Adrb3^tm1Lowl	Adrb1^tm1Bkk/Adrb1^tm1Bkk,Adrb2^tm1Bkk/Adrb2^tm1Bkk,Adrb3^tm1Lowl/Adrb3^tm1Lowl 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
Adrb1^tm1Bkk\|Adrb2^tm1Bkk\|Adrb3^tm1Lowl	Adrb1^tm1Bkk/Adrb1^tm1Bkk,Adrb2^tm1Bkk/Adrb2^tm1Bkk,Adrb3^tm1Lowl/Adrb3^tm1Lowl 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

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

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:	149

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:	57,75,101,150

Type:	Single nucleotide polymorphism
Species:	Human
Description:	The Arg¹⁶ > Gly polymorphism and the Thr¹⁶⁴ > Ile polymorphism are associated with an increased risk of severe exacerbations in patients with chronic obstructive pulmonary disease.
References:	79,147

Type:	Single nucleotide polymorphism
Species:	Human
Description:	β₂-AR polymorphisms are associated with changes in body composition and obesity. The Gln²⁷> Glu polymorphism is associated with obesity and the Arg¹⁶> Gly polymorphism with lean mass in men and the development of obesity.
References:	76

Type:	Single nucleotide polymorphism
Species:	Human
Description:	The Arg¹⁶ > Gly polymorphism is associated with an increased risk of severe adverse events in children treated with long acting β₂-AR agonists.
References:	26,166

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:	42,52

General Comments
For a review on the β-adrenoceptor polymorphisms see reference [97].

References

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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. Ahn S, Kahsai AW, Pani B, Wang QT, Zhao S, Wall AL, Strachan RT, Staus DP, Wingler LM, Sun LD et al.. (2017) Allosteric "beta-blocker" isolated from a DNA-encoded small molecule library. Proc Natl Acad Sci U S A, 114 (7): 1708-1713. [PMID:28130548]

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Richard A. Bond
Department of Pharmacological and Pharmaceutical Sciences
University of Houston
Houston
TX
77004-5515
USA

David B. Bylund
Department of Pharmacology
University of Nebraska Medical Center
Box 986260
Omaha
NE
68198-6260
USA

Douglas C. Eikenburg
Department of Pharmacology
University of Houston College of Pharmacy
Houston
TX
77204-5515
USA

J. Paul Hieble
Pharmacological Sciences
SmithKline Beecham Pharmaceuticals
PO Box 1539
King of Prussia
PA
19406-0939
USA

Rebecca Hills
(Past curator)

Kenneth P. Minneman
Department of Pharmacology
Emory University Medical School
Atlanta
GA
30322
USA

Sergio Parra
Department of Pharmacological and Pharmaceutical Sciences
University of Houston
Houston
TX
77004-5515
USA

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