Contents:
- 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  |
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| 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 |
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| 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 |
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| Associated Proteins |
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| 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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 | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| 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 | ||||||||
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| Primary Transduction Mechanisms
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| 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 |
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| 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
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| Physiological Functions
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| Physiological Consequences of Altering Gene Expression
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| Phenotypes, Alleles and Disease Models
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| Clinically-Relevant Mutations and Pathophysiology
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| General Comments |
| For a review on the β-adrenoceptor polymorphisms see reference [98]. |
References
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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]
3. 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]
4. 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]
5. 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]
6. 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]
7. 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]
8. Araujo LP, Maricato JT, Guereschi MG, Takenaka MC, Nascimento VM, de Melo FM, Quintana FJ, Brum PC, Basso AS. (2019) The Sympathetic Nervous System Mitigates CNS Autoimmunity via β2-Adrenergic Receptor Signaling in Immune Cells. Cell Rep, 28 (12): 3120-3130.e5. [PMID:31533035]
9. 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]
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Baker JG, Balaji P, Bond RA, Bylund DB, Eikenburg DC, Graham RM, Hieble JP, Hills R, Michel MC, Minneman KP, Parra S, Perez D, Summers RJ. Adrenoceptors in GtoPdb v.2024.2. IUPHAR/BPS Guide to Pharmacology CITE. 2024; 2024(2). Available from: https://doi.org/10.2218/gtopdb/F4/2024.2.
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