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	91
Mouse	7	418	18 35.1 cM	Adrb2	adrenergic receptor, beta 2	4
Rat	7	418	18q12.1	Adrb2	adrenoceptor beta 2	60

Previous and Unofficial Names

ADRB2R | ADRBR | B2AR | beta-2 adrenergic receptor | beta-2 adrenoreceptor | Adrb-2 | beta 2-AR | Gpcr7 | adrenoceptor beta 2, surface | adrenergic receptor

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
	Description:  Crystal structure of the human β2-adrenergic receptor in complex with the inverse agonist ICI 118,551 PDB Id:  3NY8 Ligand:  ICI 118551 Resolution:  2.84Å Species:  Human References:  156
	Description:  Crystal structure of the β2 adrenergic receptor-Gs protein complex PDB Id:  3SN6 Resolution:  3.2Å Species:  None References:  127
	Description:  Cholesterol bound form of human β2-adrenergic receptor PDB Id:  3D4S Ligand:  cholesterol Resolution:  2.8Å Species:  Human References:  67
	Description:  Crystal structure of the human β2-adrenergic receptor in complex with the neutral antagonist alprenolol PDB Id:  3NYA Ligand:  alprenolol Resolution:  3.16Å Species:  Human References:  156
	Description:  Crystal structure of the human β2-adrenoceptor PDB Id:  2R4S Resolution:  3.4Å Species:  Human References:  126
	Description:  Crystal structure of a methylated β2-Adrenergic Receptor-Fab complex PDB Id:  3KJ6 Resolution:  3.4Å Species:  Human References:  28
	Description:  Crystal structure of the human β2-adrenoceptor PDB Id:  2R4R Resolution:  3.4Å Species:  Human References:  126
	Description:  High resolution crystal structure of human β2-adrenergic G protein-coupled receptor. N.B. the representation of carazolol on PBD shows the S isomer, which our ligand entry specifies the racemate. PDB Id:  2RH1 Ligand:  carazolol Resolution:  2.4Å Species:  Human References:  40
	Description:  Irreversible agonist-β2-adrenoceptor complex. N.B. agonist utilised was a procaterol derivative containing a covalent crosslinker. PDB Id:  3PDS Resolution:  3.5Å Species:  Human References:  130
	Description:  Structure of β2-adrenoceptor bound to carazolol and an intracellular allosteric antagonist. PDB Id:  5X7D Ligand:  carazolol Resolution:  2.7Å Species:  Human References:  104
	Description:  Crystal structure of human β2 adrenergic receptor bound to salmeterol and Nb71. PDB Id:  6MXT Ligand:  salmeterol Resolution:  2.96Å Species:  Human References:  109
	Description:  Structure of β2 adrenoceptor bound to BI167107 and an engineered nanobody PDB Id:  4LDE Ligand:  BI-167107 Resolution:  2.79Å Species:  Human References:  128
	Description:  Structure of β2-adrenoceptor bound to a covalent agonist and an engineered nanobody. PDB Id:  4QKX Resolution:  3.3Å Species:  Human References:  157

Associated Proteins

Interacting Proteins Name Effect References β2-adrenoceptor 6,30,69,93,114 β1-adrenoceptor 96-97,114,166 β3-adrenoceptor 30 α1D-adrenoceptor 152 α2A-adrenoceptor 93 5-HT4 receptor 25 δ receptor 88,113 κ receptor 88 μ receptor 93 EP1 receptor 112 B2 receptor 64 CXCR4 95 CB1 receptor 79,93 mouse 71 (M71) Olfactory receptor 65 D1 receptor 93 OT receptor 163-164 epidermal growth factor receptor 110 GluA1 87 AT1 receptor 19,86 A1 receptor 39 Insulin receptor 142

Natural/Endogenous Ligands
(-)-adrenaline
(-)-noradrenaline
Zn2+
Comments: Adrenaline exhibits greater potency than noradrenaline

Potency order of endogenous ligands (Human)

(-)-adrenaline > (-)-noradrenaline

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference CHF-6366 Hs Agonist 11.4 pKd 38 ⤷ pKd 11.4 (Kd 4x10-12 M) [38] Description: Binding to human cloned β2 receptor using 125I-cyanopindolol as tracer [3H]CGP12177 Hs Partial agonist 9.8 pKd 15 ⤷ pKd 9.8 (Kd 1.44x10-10 M) [15] Description: Binding to human &beta2-adrenoceptor expressed in CHO-K1 cells, in a whole cell binding assay. orciprenaline Hs Agonist 5.3 pKd 139 ⤷ pKd 5.3 (Kd 4.81x10-6 M) [139] pindolol Hs Partial agonist 9.4 pKi 92 ⤷ pKi 9.4 (Ki 4x10-10 M) [92] salmeterol Hs Partial agonist 6.8 – 9.3 pKi 14,18,46 ⤷ pKi 6.8 – 9.3 [14,18,46] zinterol Hs Agonist 8.0 pKi 14 ⤷ pKi 8.0 [14] clenbuterol Hs Full agonist 7.4 – 7.9 pKi 14,18,90 ⤷ pKi 7.4 – 7.9 [14,18,90] indacaterol Hs Agonist 7.4 – 7.8 pKi 21-22 ⤷ pKi 7.4 – 7.8 [21-22] BRL35135 Hs Partial agonist 7.4 pKi 14 ⤷ pKi 7.4 [14] procaterol Hs Agonist 7.1 pKi 14 ⤷ pKi 7.1 [14] ractopamine Hs Partial agonist 6.6 – 6.9 pKi 14,46,82 ⤷ pKi 6.6 – 6.9 [14,46,82] Description: Inhibitory constant determined from a standard radioligand displacement assay using human β2-adrenoceptors expressed in Sf-9 cells and [3H]CGP1217 as tracer. isoprenaline Hs Full agonist 6.4 – 6.6 pKi 14-15,134 ⤷ pKi 6.4 – 6.6 [14-15,134] BRL 37344 Hs Partial agonist 6.5 pKi 14 ⤷ pKi 6.5 [14] fenoterol Hs Agonist 5.5 – 7.0 pKi 9,14,18,46 ⤷ pKi 5.5 – 7.0 [9,14,18,46] (-)-adrenaline Hs Full agonist 6.0 – 6.2 pKi 14,54,74,84 ⤷ pKi 6.0 – 6.2 [14,54,74,84] salbutamol Hs Partial agonist 5.3 – 6.1 pKi 13-14,18,46,82,138 ⤷ pKi 5.3 – 6.1 [13-14,18,46,82,138] ephedrine Hs Partial agonist 5.6 pKi 84 ⤷ pKi 5.6 [84] terbutaline Hs Partial agonist 5.5 – 5.6 pKi 13-14 ⤷ pKi 5.5 – 5.6 [13-14] noradrenaline Hs Full agonist 5.4 pKi 101 ⤷ pKi 5.4 [101] (-)-noradrenaline Hs Agonist 4.6 – 5.4 pKi 14,54,74 ⤷ pKi 4.6 – 5.4 [14,54,74] olodaterol Hs Agonist 10.0 pEC50 29 ⤷ pEC50 10.0 (IC50 1x10-10 M) [29] BI-167107 Hs Agonist 10.0 pEC50 73 ⤷ pEC50 10.0 (EC50 1x10-10 M) [73] Description: Determined in an intracellular cAMP accumulation assay in CHO-K1 cells expressing hβ2-AR salmeterol Hs Partial agonist 9.2 – 9.9 pEC50 14,21 ⤷ pEC50 9.2 – 9.9 [14,21] zinterol Hs Agonist 9.5 pEC50 14 ⤷ pEC50 9.5 [14] vilanterol Hs Agonist 9.4 pEC50 123 ⤷ pEC50 9.4 (EC50 3.98x10-10 M) [123] clenbuterol Hs Agonist 9.2 pEC50 14 ⤷ pEC50 9.2 [14] formoterol Hs Agonist 7.8 – 10.1 pEC50 3,14,18,21,103 ⤷ pEC50 7.8 – 10.1 [3,14,18,21,103] BRL35135 Hs Partial agonist 8.7 pEC50 14 ⤷ pEC50 8.7 [14] procaterol Hs Agonist 8.4 pEC50 14 ⤷ pEC50 8.4 [14] isoprenaline Hs Full agonist 8.2 pEC50 14-15 ⤷ pEC50 8.2 [14-15] indacaterol Hs Agonist 8.1 pEC50 21 ⤷ pEC50 8.1 [21] (-)-adrenaline Hs Full agonist 7.9 pEC50 14 ⤷ pEC50 7.9 [14] ractopamine Hs Partial agonist 7.6 – 7.8 pEC50 14,46 ⤷ pEC50 7.6 – 7.8 [14,46] fenoterol Hs Agonist 6.1 – 8.9 pEC50 14,46 ⤷ pEC50 6.1 – 8.9 [14,46] terbutaline Hs Partial agonist 7.3 pEC50 14 ⤷ pEC50 7.3 [14] salbutamol Hs Partial agonist 6.3 – 7.7 pEC50 14,46 ⤷ pEC50 6.3 – 7.7 [14,46] BRL 37344 Hs Partial agonist 6.9 pEC50 14 ⤷ pEC50 6.9 [14] (-)-noradrenaline Hs Agonist 6.4 pEC50 14 ⤷ pEC50 6.4 [14] solabegron Hs Agonist 5.9 pEC50 153 ⤷ pEC50 5.9 [153] mirabegron Hs Agonist <5.0 – 5.2 pEC50 47,146 ⤷ pEC50 5.0 – 5.2 [47,146] pEC50 <5.0 (EC50 >1x10-5 M) [146] mirabegron Rn Agonist 5.0 pEC50 47 ⤷ pEC50 5.0 [47] 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 - - 14 ⤷ [14]
View species-specific agonist tables
Agonist Comments
Although [138] states that salbutamol was tested, in fact R-(-)salbutamol (levosalbutamol) was tested. pKi values are from binding studies and pEC50 from functional studies (usually cAMP generation) which give a better idea of relative experimental or clinical potency. Salbutamol, terbutaline and fenoterol are examples of short acting β agonists (SABAs), salmeterol and formoterol are long acting β agonists (LABAs) and indacaterol, olodaterol abediterol and vilanterol are ultra long acting β agonists (ultra-LABAs) [26]. BRL37344 and BRL35135 are classified as β3-AR selective agonists (rodent selective) but have significant actions at β2-AR [118]. Clenbuterol is included on the World Anti-Doping Authority's list of banned substances due to its popularity as a drug used by bodybuilders and for weight loss. Clinical uses: β2-AR agonists are widely used in asthma and COPD. Adrenaline is used as a bolus injection in cardiac arrest, anaphylaxis and as an intravenous infusion for shock.

Antagonists
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference butoxamine Rn Antagonist 6.4 pKB 72 ⤷ pKB 6.4 (KB 3.55x10-7 M) [72] butoxamine Hs Antagonist 6.2 – 6.5 pKB 14,32,149 ⤷ pKB 6.2 – 6.5 [14,32,149] [125I]ICYP Hs Antagonist 11.1 – 11.4 pKd 108,134,145 ⤷ pKd 11.1 – 11.4 (Kd 7.9x10-12 M) It is necessary to use an excess of a β1-adrenoceptor-selective ligand such as CGP20712A in combination with this radioligand in order to allow visualisation of β2-adrenoceptor binding in native tissues. [108,134,145] 7-methylcyanopindolol Hs Inverse agonist 10.4 pKd 133 ⤷ pKd 10.4 [133] [3H]dihydroalprenolol Hs Antagonist 10.1 pKd 145 ⤷ pKd 10.1 [145] [3H]CGP12177 Hs Partial agonist 9.8 pKd 15 ⤷ pKd 9.8 [15] carazolol Hs Antagonist 9.9 – 10.5 pKi 14,131 ⤷ pKi 9.9 – 10.5 [14,131] timolol Hs Antagonist 9.7 pKi 13 ⤷ pKi 9.7 [13] carvedilol Hs Antagonist 9.4 – 9.9 pKi 13,36 ⤷ pKi 9.4 – 9.9 [13,36] pindolol Hs Antagonist 9.4 pKi 92 ⤷ pKi 9.4 [92] CGP 12177 Hs Antagonist 9.4 pKi 13,15,108 ⤷ pKi 9.4 [13,15,108] ICI 118551 Hs Inverse agonist 9.2 – 9.5 pKi 13,17,108 ⤷ pKi 9.2 – 9.5 [13,17,108] propranolol Hs Antagonist 9.1 – 9.5 pKi 13,17,82,108 ⤷ pKi 9.1 – 9.5 [13,17,82,108] bunolol Hs Antagonist 9.3 pKi 10 ⤷ pKi 9.3 (Ki 5.5x10-10 M) [10] bupranolol Hs Antagonist 8.3 – 9.9 pKi 13,36,108 ⤷ pKi 8.3 – 9.9 [13,36,108] alprenolol Hs Partial agonist 9.0 pKi 13 ⤷ pKi 9.0 [13] SR59230A Hs Antagonist 8.5 – 9.3 pKi 13,36 ⤷ pKi 8.5 – 9.3 [13,36] labetalol Hs Partial agonist 8.0 pKi 10,13 ⤷ pKi 8.0 (Ki 1.1x10-8 M) [10,13] nebivolol Hs Antagonist 7.9 – 8.0 pKi 14,52 ⤷ pKi 7.9 – 8.0 [14,52] Description: Radioligand binding nadolol Hs Antagonist 7.0 – 8.6 pKi 13,36 ⤷ pKi 7.0 – 8.6 [13,36] betaxolol Hs Antagonist 7.2 – 8.2 pKi 14,108,136 ⤷ pKi 7.2 – 8.2 [14,108,136] NIP Hs Antagonist 7.5 pKi 108 ⤷ pKi 7.5 [108] propafenone Hs Antagonist 7.4 pKi 10 ⤷ pKi 7.4 (Ki 3.6x10-8 M) [10] sotalol Hs Antagonist 6.5 – 6.9 pKi 10,13 ⤷ pKi 6.5 – 6.9 [10,13] metoprolol Hs Antagonist 6.3 – 6.9 pKi 13,108 ⤷ pKi 6.3 – 6.9 [13,108] butoxamine Rn Antagonist 6.3 – 6.5 pKi 32,149 ⤷ pKi 6.3 – 6.5 (Ki 4.68x10-7 – 3.09x10-7 M) [32,149] cicloprolol Hs Antagonist 6.2 pKi 108 ⤷ pKi 6.2 [108] NIHP Hs Antagonist 6.0 pKi 108 ⤷ pKi 6.0 [108] atenolol Hs Antagonist 5.6 – 6.0 pKi 13,108 ⤷ pKi 5.6 – 6.0 [13,108] LK 204-545 Hs Antagonist 5.2 pKi 108 ⤷ pKi 5.2 [108]
View species-specific antagonist tables
Antagonist Comments
The approved drug propranolol is categorised as a non-selective β-adrenoceptor antagonist but is slightly selective for β2-AR and has very low affinity for β3-AR. Propranolol also behaves as a biased agonist in several studies- an inverse agonist decreasing cAMP whilst stimulating β-arrestin and gene transcription [11,16]. Carvedilol is a non-selective β-AR and α1-AR antagonist used to treat cardiac failure. Carvedilol has been suggested to be a β-arrestin biased agonist [161] but this characteristic has been challenged [23] with evidence supporting low efficacy activation of Gs coupled β2-adrenoceptors as the explanation. Several 'cardioselective' or β1-AR selective antagonists such as atenolol and metoprolol have appreciable affinity for β2-AR. Several antagonists may display partial agonist activity at β2-AR including pindolol, carazolol, bucindolol, nebivolol and carvedilol [14] in assays where there is significant receptor reserve or receptor over-expression. ICI118551 is the most selective β2-AR antagonist currently available but is only used in in vitro studies where it displays ~300 fold selectivity vs. the other 8 adrenoceptor subtypes. Although often described as a β3-AR selective antagonist, SR59230A has little selectivity and is a high affinity antagonist at β2-AR [115]. The main action of propafenone is to block voltage gated Na+ channels (see the Voltage-gated sodium channels family in the Ion Channels section of this website for further details) but is also a weak β-adrenoceptor antagonist. Some cell systems (e.g. HEK cells) commonly used to study the pharmacology of β-AR subtypes express functionally active β2-AR populations. Clinical uses: not directly used, but effects of several β-AR antagonists used clinically (see β1-AR) are also likely to occur through β2-AR (e.g. migraine, portal hypertension, anxiety, glaucoma, thyrotoxicosis, infantile haemangioma).

Allosteric Modulators
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Value Parameter Reference Zn2+ Hs Positive 5.3 pKi 143-144 ⤷ pKi 5.3 [143-144] Zn2+ Hs Negative 3.3 pKi 143-144 ⤷ pKi 3.3 [143-144] AS408 N/A - - - 105 ⤷ [105] compound 6 [PMID: 29769246] Hs Positive - - 121 ⤷ cooperativity [121]
View species-specific allosteric modulator tables
Allosteric Modulator Comments
Zn2+ appears to have both positive and negative effects on agonist affinity. At low concentrations it appears to enhance agonist affinity and agonist-stimulated cAMP accumulation. At high concentrations Zn2+ inhibits agonist binding but slows antagonist dissociation [143-144]. Cmpd-6 is a positive allosteric modulator of the pharmacological activity of carvedilol at the β2-AR [121].

Immunopharmacology Comments

β2-ARs are expressed on innate and adaptive immune cells of humans and rodents, and are reported to have an immuno-modulating effect [48]. There is a large literature on the role of autoantibodies to β2-AR associated with a variety of disease processes [31,37,75,78,160].

Cell Type Associations

Immuno Cell Type:  B cells Cell Ontology Term:   B cell (CL:0000236) Comment:  B cells from patients with rheumatoid arthritis express lower levels of β2-ARs compared with healthy subjects. References:  12

Immuno Cell Type:  Dendritic cells Cell Ontology Term:   dendritic cell (CL:0000451) Comment:  β2-AR agonist-exposed mature dendritic cells have a reduced ability to cross-present protein antigens while retaining exogenous peptide presentation capability. This effect is mediated through a Gi/o inhibitory pathway. References:  70

Immuno Cell Type:  T cells Cell Ontology Term:   CD8-positive, alpha-beta T cell (CL:0000625) regulatory T cell (CL:0000815) Comment:  Activation of β2-ARs enhances retention-promoting signals through CCR7 and CXCR4 and inhibits lymphocyte (T cells and other lymphocyte lineages) egress from lymph nodes. In models of T cell-mediated inflammatory diseases, β2-AR-mediated signals inhibit lymph node egress of antigen-primed T cells and reduce their recruitment into peripheral tissues [119].CD8+ T cells (CL:0000625): CD8+ T cells from patients with rheumatoid arthritis express lower levels of β2-ARs compared with healthy subjects [12]. Treg cells (CL:0000815): β2-AR agonist increases Treg-cell suppressive function associated with decreased IL-2 mRNA levels in responder CD4+ T cells and improved Treg-cell-induced conversion of CD4+ Foxp3- cells into Foxp3+ induced Treg cells [62]. References:  12,62

Immuno Cell Type:  Mast cells Cell Ontology Term:   mast cell (CL:0000097) Comment:  Mast cell histamine release was increased in coculture with human airways smooth muscle cells and this was enhanced by β2-AR agonists. Inhibition of mast cell mediator release by β2-AR-agonists was reduced in coculture. β2-AR agonists did not prevent smooth muscle cell contraction when mast cells were present, but this was reversed by corticosteroids. References:  99

Immuno Cell Type:  Macrophages & monocytes Cell Ontology Term:   macrophage (CL:0000235) monocyte (CL:0000576) Comment:  Monocytes (CL:0000576): Monocytes from patients with rheumatoid arthritis express lower levels of β2-ARs compared with healthy subjects [12]. Monocytes from high-fat diet-induced obese mice presented higher expression levels of pro-inflammatory cytokines and a higher % of monocytes with a pro-inflammatory phenotype than those from lean animals. β2-AR stimulation induced a shift towards an anti-inflammatory activity profile and phenotype in obese mice, whereas it induced a shift towards a pro-inflammatory activity profile and phenotype in lean mice [55]. Treatment of monocytes with the β2-AR agonist clenbuterol inhibits differentiation into dendritic cells, reduces the % of CD1a+ immature DCs, while increasing the frequency of monocytes retaining CD14 surface expression [59]. Macrophages (CL:0000235): Immune cell β2-ARs are important for proinflammatory macrophage infiltration to the heart in a chronic isoprenaline administration model of heart failure. Mice lacking immune cell β2-AR have decreased proinflammatory macrophage infiltration to the heart, decreased cardiac injury and cardiomyocyte death, decreased interstitial fibrosis and hypertrophy and improved function [147]. References:  12,55,59,147

Immuno Process Associations

Immuno Process:  Antigen presentation

Immuno Process:  Immune regulation

Immuno Process:  Cellular signalling

Immuno Process:  Inflammation

Primary Transduction Mechanisms
Transducer	Effector/Response
Gs family
Comments:  Stimulation of adenylate cyclase (AC) causes the conversion of ATP into cAMP. This activates protein kinase A, which in turn phosphorylates several substrates, for example L-type Ca2+ channels. In skeletal muscle cAMP signalling is associated with mTORC2 activation that promotes GLUT4 translocation and increased glucose uptake.
References:  100,135,140,159

Secondary Transduction Mechanisms
Transducer	Effector/Response
Gi/Go family	Guanylate cyclase stimulation
Comments:  Adenylyl cyclase inhibition reduces the conversion of ATP to cAMP. Stimulation of guanylyl cyclase (GC) causes an increase in cGMP levels, and subsequent activation of protein kinase G.
References:  100,162

Tissue Distribution
55 organs and tissues. Species:  Human Technique:  RNA expression. References:  20
Heart: right atrial appendage, left atrial free wall, left ventricular papillary muscle and pericardium, atrioventricular node, bundle of His, interatrial and interventricular septa, right atrium, left ventricular free wall, right ventricular free wall, right atrium from an area near the atrioventricular node and cardiac nerves. Intimal surface of coronary arteries. Species:  Human Technique:  Autoradiography References:  34,49,141
Lung >> spleen > kidney > heart > brain > skeletal muscle > liver. Species:  Mouse Technique:  Radioligand binding. References:  5
Brain: medial prefrontal cortex. Species:  Mouse Technique:  Immunohistochemistry in GABAergic interneurons in medial prefrontal cortex, including parvalbumin (PV)-, calretinin (CR)-, calbindin D-28k (CB)-, somatostatin (SST)- and reelin-immunoreactive (ir) interneurons. β2-AR most likely in SSTR-ir neurons. References:  106
Lung >> skeletal muscle > spleen > kidney > heart > brain > liver. Species:  Mouse Technique:  in situ hybridisation. References:  5
Lung > heart. Species:  Rat Technique:  Radioligand binding. References:  116
Subcellular distribution in ventricular myocytes. Species:  Rat Technique:  Ventricular myocytes and detubulated myocytes: Ca2+ transients and cell shortening: β2-AR at surface sarcolemma. References:  44
Diabetic heart. Species:  Rat Technique:  Radioligand binding, western blot, mRNA. References:  50,66
Brain: Caudate, cortex, cerebellum, hippocampus, diencephalon. Species:  Rat Technique:  Radioligand binding. References:  116
Internal anal sphincter (IAS) smooth muscle. Species:  Rat Technique:  Western blotting. References:  100

Expression Datasets
Show »« Hide 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
GTPase activity. Species:  Human Tissue:  HEK293 cells. Response measured:  GTP hydrolysis using chemiluminescence-based GTPase-Glo Assay (Promega) References:  2
Measurement of cAMP levels in CHO-K1 cells expressing the human β2 receptor. Species:  Human Tissue:  CHO-K1 cells. Response measured:  cAMP accumulation. References:  134
Measurement of cAMP levels in rat heart and lung tissue. Species:  Rat Tissue:  Heart and lung. Response measured:  cAMP accumulation. References:  116
Measurement of cAMP levels in human lung epithelial cell lines. Species:  Human Tissue:  Calu-3 and 16HBE14o- cell lines. Response measured:  cAMP accumulation. References:  1
Measurement of cAMP levels in a human macrophage cell line. Species:  Human Tissue:  U937 cells. Response measured:  cAMP accumulation. References:  83
Measurement of cAMP levels in Sf9 insect cells transfected with the human β2-adrenoceptor. Species:  Human Tissue:  Sf9 cells. Response measured:  cAMP accumulation. References:  135
The trachea of an anesthetized mouse is intubated and airway resistance is measured in response to intravenously injected agonists. Species:  Mouse Tissue:  Lung. Response measured:  Decrease in airway resistance. References:  35
Measurement of cAMP and Ca2+ levels in CHW fibroblast cells endogenously expressing Gs, AC and PKA and transfected with both the β2-adrenoceptor and the L-type Ca2+ channel. Species:  Human Tissue:  CHW-1102 fibroblast cells. Response measured:  PTX-insensitive cAMP and Ca2+ accumulation. References:  165
Measurement of LPS-induced cytokine release (TNFα and Il-10) from human U937 macrophage cells when treated with a β2-adrenoceptor agonist. Species:  Human Tissue:  U937 cells. Response measured:  Inhibition of TNFα release, stimulation of Il-10 release. References:  83
β-arrestin recruitment. Species:  Human Tissue:  HEK293 cells. Response measured:  Interaction monitored using BRET between β-arrestin2-GFP10 and β2-AR-RlucII. References:  81
cAMP production in skeletal muscle. Species:  Rat Tissue:  L6 skeletal muscle cells. Response measured:  cAMP accumulation using antibody-based flashplate assay. References:  120
Measurement of cAMP levels in rat heart and lung tissue. Species:  Rat Tissue:  Heart and lung. Response measured:  cAMP accumulation. References:  116
Measurement of cAMP levels in CHO-K1 cells expressing the human β2 receptor. Species:  Human Tissue:  CHO-K1 cells. Response measured:  Whole cell binding using [3H]CGP12177, cAMP accumulation. References:  14
β2-adrenoceptor agonist profiling reveals biased signalling phenotypes for the β2-adrenoceptor with possible implications for the treatment of asthma. Species:  Human Tissue:  Glo-sensor cAMP accumulation, pathhunter β-arrestin recruitment, BRET G protein recruitment, ERK1/2 phosphorylation, receptor internalization and endosomal localisation. Response measured:  HEK293 cells expressing human β2-AR. References:  46
Measurement of cAMP levels in HEK-293 cell lines expressing the Glosensor (Promega) cAMP reporter, the ICUE2 cAMP reporter and the human β2-AR . Species:  Human Tissue:  HEK293 cells. Response measured:  cAMP accumulation measured using chemiluminescence-based cAMP biosensor. References:  2
β-arrestin recruitment and endocytosis. Species:  Human Tissue:  HEK293 cells. Response measured:  Recruitment monitored using PathHunter, a chemiluminescence-based enzyme fragment complementation assay: endocytosis measured by active endocytosis assay (DiscoverX). References:  2
Intracellular Ca2+ mobilisation involving PLC and IP3 but not cAMP, Gαs or Gαi. Species:  Human Tissue:  HEK293 cells endogenously expressing β2-AR. Response measured:  Fluorescence-based Ca2+ flux assays References:  56
Receptor heteromer formation. Species:  Human Tissue:  HEK293 cells. Response measured:  Interaction between GPCRs monitored using BRET. References:  86
Measurement of cAMP levels in HEK-293 cells using a FRET based biosensor. Species:  Human Tissue:  HEK293 cells. Response measured:  cAMP accumulation measured using FRET-based cAMP biosensor. References:  155
Glucose uptake in skeletal muscle. Species:  Rat Tissue:  L6 skeletal muscle cells. Response measured:  Glucose uptake measured using [3H]2-deoxyglucose. References:  132

Physiological Functions
Stimulation of aqueous humor formation and outflow. Species:  Human Tissue:  Eye. References:  122
Hypotension, lowering of blood pressure. Species:  Mouse Tissue:  Blood vessels. References:  41
Presynaptic facilitation of noradrenlaine release from sympathetic nerves. Species:  Rat Tissue:  Isolated perfused kidney. References:  94
Bronchodilation. Species:  Mouse Tissue:  Lung. References:  35
Uterine relaxation. Species:  Human Tissue:  Myometrial muscle. References:  107
Inhibition of apoptosis via a PTX-sensitive G-protein. Apoptosis via Gs and adenylyl cyclase. Species:  Rat Tissue:  Ventricular cardiomyocytes. References:  125
Synaptic plasticity and memory. Species:  Mouse Tissue:  Brain. References:  45,57,68,85
Coronary vasodilation. Species:  Human Tissue:  Coronary blood vessels. References:  124,154
Positive inotropic, chronotropic and lusitropic effects in atria. Species:  Human Tissue:  Right atrial appendage. References:  117
All the β-adrenoceptors mediate relaxation of the internal anal sphincter (IAS) smooth muscle, the β2 subtype achieving this via both the Gs/cAMP pathway and the Gi/o/cGMP pathway. Species:  Rat Tissue:  Internal anal sphincter (IAS) smooth muscle. References:  100
Cardioprotective effects. Species:  Mouse Tissue:  Cardiomyocytes from mice with chemically induced cardiotoxicity. References:  24,137
Glucose release from liver. Species:  Human Tissue:  Liver. References:  33,63
Modulation of kidney function in humans and other animals. Species:  Human Tissue:  Kidney. References:  89
Bronchodilation in human and other animals. Species:  Human Tissue:  Lung. References:  158
Glucose uptake in skeletal muscle. Species:  Rat Tissue:  L6 skeletal muscle cells. References:  132

Physiological Consequences of Altering Gene Expression
Studies involving mice overexpressing the β2-adrenoceptor show alterations in heart beat and contractile response. Species:  Human Tissue:  Technique:  Transgenesis. References:  71
Studies involving β2-adrenoceptor knockouts have only shown obvious physiological changes when under cardiovascular stress conditions. This subtype is thought not to be involved in postnatal development but does mediate peripheral vascular resistance and energy metabolism. Species:  Mouse Tissue:  Technique:  Gene targeting in embryonic stem cells. References:  41
Transgenic (TG) mice overexpressing the β2-adrenoceptor in airway smooth muscle exhibit enhanced β2 signalling and an increase in basal cAMP levels. Tracheal rings from the TG mice showed increased relaxation to a β-agonist, and in vivo studies showed resistance to methacholine-induced bronchoconstriction. Overall, a decrease in bronchial hyperresponsiveness was seen in the TG mice: an anti-asthmatic state. Species:  Mouse Tissue:  Technique:  Transgenesis. References:  111
β1- and β2-adrenoceptor double knockout mice appear to have unaltered basal heart rate, blood pressure and metabolic rate. Stimulation of these receptors by agonists or exercise reveals they exhibit a normal exercise capacity but at a submaximal heart rate. Species:  Mouse Tissue:  Technique:  Gene targeting in embryonic stem cells. References:  129
β2-AR knockout mice show limited T cell autoimmunity in EAE through a mechanism mediated by the suppression of IL-2, IFN-γ, and GM-CSF production via inducible cAMP early repressor (ICER). Species:  Mouse Tissue:  Technique:  Gene targeting in embryonic stem cells. References:  8
β1-/β2-AR knockout mice show an enhanced inflammatory response to injury, that delayed early muscle regeneration, but enhanced myoblast proliferation later during regeneration to produce a similar functional recovery to controls by 14 days post-injury. Species:  Mouse Tissue:  Skeletal muscle. Technique:  Gene targeting in embryonic stem cells. References:  42
β2-AR knockout mice do not develop muscle LIM protein cardiomyopathy due to positive modulation of Ca2+ due to removal of inhibitory Gisignaling and increased phosphorylation of troponin I and phospholamban. Species:  Mouse Tissue:  Heart. Technique:  References:  42
β2-AR knockout mice show preserved cold- and diet-induced adaptive thermogenesis but disrupted glucose homeostasis possibly by accelerating hepatic glucose production and insulin secretion. Species:  Mouse Tissue:  Metabolism. Technique:  Gene targeting in embryonic stem cells. References:  51
Immune cell-expressed β2-AR play an essential role in regulating the early inflammatory repair response to acute myocardial injury by facilitating cardiac leukocyte infiltration. Species:  Mouse Tissue:  Heart. Technique:  Gene targeting in embryonic stem cells. References:  61

Phenotypes, Alleles and Disease Models

Mouse data from MGI

Show »« Hide 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: