Beta-2 adrenergic receptor

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Adrenoceptor beta 2, surface
Crystallographic structure of the ?2-adrenergic receptor depicted as a green cartoon and the bound partial inverse agonist carazolol ligand as spheres (carbon atom = grey, oxygen = red, nitrogen = blue). The phospholipid bilayer is depicted as blue spheres (phosphate head groups) and yellow lines (lipid sidechains).[1][2]
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM109690 MGI87938 HomoloGene30948 IUPHAR: β2-adrenoceptor ChEMBL: 210 GeneCards: ADRB2 Gene
RNA expression pattern
PBB GE ADRB2 206170 at tn.png
More reference expression data
Species Human Mouse
Entrez 154 11555
Ensembl ENSG00000169252 ENSMUSG00000045730
UniProt P07550 P18762
RefSeq (mRNA) NM_000024 NM_007420
RefSeq (protein) NP_000015 NP_031446
Location (UCSC) Chr 5:
148.21 – 148.21 Mb
Chr 18:
62.18 – 62.18 Mb
PubMed search [1] [2]

The beta-2 adrenergic receptor2 adrenoreceptor), also known as ADRB2, is a beta-adrenergic receptor within a cell membrane which reacts with adrenaline (epinephrine) as a hormone or neurotransmitter affecting muscles or organs. The official symbol for the human gene encoding the β2 adrenoreceptor is ADRB2.[3]


The ADRB2 gene is intronless. Different polymorphic forms, point mutations, and/or downregulation of this gene are associated with nocturnal asthma, obesity and type 2 diabetes.[4]


The 3D crystallographic structure (see figure and links to the right) of the β2-adrenergic receptor has been determined[5][1][2] by making a fusion protein with lysozyme to increase the hydrophillic surface area of the protein for crystal contacts.


This receptor is directly associated with one of its ultimate effectors, the class C L-type calcium channel CaV1.2. This receptor-channel complex is coupled to the Gs G protein, which activates adenylyl cyclase, catalysing the formation of cyclic adenosine monophosphate (cAMP) which then activates protein kinase A, and the counterbalancing phosphatase PP2A. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling. A two-state biophysical and molecular model has been proposed to account for the pH and REDOX sensitivity of this and other GPCRs.[6]

Beta-2 Adrenergic Receptors have also been found to couple with Gi, possibly providing a mechanism by which response to ligand is highly localized within cells. In contrast, Beta-1 Adrenergic Receptors are coupled only to Gs, and stimulation of these results in a more diffuse cellular response.[7] This appears to be mediated by cAMP induced PKA phosphorylation of the receptor.[8]


Actions of the β2 receptor include:

Muscular system[edit]

Tissue/Effect Function

Smooth muscle relaxation in:


inhibits labor
GI tract (decreases motility) Delay digestion during fight-or-flight response Insulin secretion from pancreas, leading to overall lower levels of blood glucose

detrusor urinae muscle of bladder wall[9] This effect is stronger than the alpha-1 receptor effect of contraction.

Delay need of micturition
seminal tract[10]
bronchi[11] Facilitate respiration (agonists can be useful in treating asthma)
Increase perfusion of target organs needed during fight-or-flight
striated muscle Tremor[10] (via PKA mediated facilitation of presynaptic Ca2+ influx leading to acetylcholine release)
Increased mass and contraction speed[10] fight-or-flight
glycogenolysis[10] provide glucose fuel

Circulatory system[edit]


In the normal eye, beta-2 stimulation by salbutamol increases intraocular pressure via net:

In glaucoma, drainage is reduced ( open-angle glaucoma) or blocked completely (closed-angle glaucoma). In such cases, beta-2 stimulation with its consequent increase in humour production is highly contra-indicated, and conversely, a topical beta-2 antagonist such as timolol may be employed.

Digestive system[edit]




(Beta blockers)

* denotes selective agonists to the receptor.


Beta-2 adrenergic receptor has been shown to interact with:

See also[edit]


  1. ^ a b PDB 2RH1; Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Kuhn P, Weis WI, Kobilka BK, Stevens RC (2007). "High-resolution crystal structure of an engineered human ?2-adrenergic G protein-coupled receptor". Science 318 (5854): 1258–65. doi:10.1126/science.1150577. PMC 2583103. PMID 17962520. 
  2. ^ a b Rosenbaum DM, Cherezov V, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, Yao XJ, Weis WI, Stevens RC, Kobilka BK (2007). "GPCR engineering yields high-resolution structural insights into ?2-adrenergic receptor function". Science 318 (5854): 1266–73. doi:10.1126/science.1150609. PMID 17962519. 
  3. ^ "Entrez Gene: ADRB2 adrenoceptor beta 2, surface". Retrieved 8 February 2015. 
  4. ^ "Entrez Gene: ADRB2 adrenergic, beta-2-, receptor, surface". 
  5. ^ Rasmussen S, Choi H, Rosenbaum D, Kobilka T, Thian F, Edwards P et al. (Nov 2007). "Crystal structure of the human beta2 adrenergic G-protein-coupled receptor". Nature 450 (7168): 383–7. Bibcode:2007Natur.450..383R. doi:10.1038/nature06325. PMID 17952055. 
  6. ^ Rubenstein L, Zauhar R, Lanzara R (Dec 2006). "Molecular dynamics of a biophysical model for beta2-adrenergic and G protein-coupled receptor activation". Journal of Molecular Graphics & Modelling 25 (4): 396–409. doi:10.1016/j.jmgm.2006.02.008. PMID 16574446. 
  7. ^ Chen-Izu Y, Xiao R, Izu L, Cheng H, Kuschel M, Spurgeon H et al. (Nov 2000). "G(i)-dependent localization of beta(2)-adrenergic receptor signaling to L-type Ca(2+) channels". Biophysical Journal 79 (5): 2547–56. Bibcode:2000BpJ....79.2547C. doi:10.1016/S0006-3495(00)76495-2. PMC 1301137. PMID 11053129. 
  8. ^ Zamah A, Delahunty M, Luttrell L, Lefkowitz R (Aug 2002). "Protein kinase A-mediated phosphorylation of the beta 2-adrenergic receptor regulates its coupling to Gs and Gi. Demonstration in a reconstituted system". The Journal of Biological Chemistry 277 (34): 31249–56. doi:10.1074/jbc.M202753200. PMID 12063255. 
  9. ^ von Heyden B, Riemer R, Nunes L, Brock G, Lue T, Tanagho E (1995). "Response of guinea pig smooth and striated urethral sphincter to cromakalim, prazosin, nifedipine, nitroprusside, and electrical stimulation". Neurourology and Urodynamics 14 (2): 153–68. doi:10.1002/nau.1930140208. PMID 7540086. 
  10. ^ a b c d e Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4.  Page 163
  11. ^ a b c d e f Fitzpatrick, David; Purves, Dale; Augustine, George (2004). "Table 20:2". Neuroscience (Third ed.). Sunderland, Mass: Sinauer. ISBN 0-87893-725-0. 
  12. ^ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4.  Page 270
  13. ^ Elenkov I, Wilder R, Chrousos G, Vizi E (Dec 2000). "The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system". Pharmacological Reviews 52 (4): 595–638. PMID 11121511. 
  14. ^ Fan G, Shumay E, Wang H, Malbon C (Jun 2001). "The scaffold protein gravin (cAMP-dependent protein kinase-anchoring protein 250) binds the beta 2-adrenergic receptor via the receptor cytoplasmic Arg-329 to Leu-413 domain and provides a mobile scaffold during desensitization". The Journal of Biological Chemistry 276 (26): 24005–14. doi:10.1074/jbc.M011199200. PMID 11309381. 
  15. ^ Shih M, Lin F, Scott J, Wang H, Malbon C (Jan 1999). "Dynamic complexes of beta2-adrenergic receptors with protein kinases and phosphatases and the role of gravin". The Journal of Biological Chemistry 274 (3): 1588–95. doi:10.1074/jbc.274.3.1588. PMID 9880537. 
  16. ^ McVey M, Ramsay D, Kellett E, Rees S, Wilson S, Pope A et al. (Apr 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". The Journal of Biological Chemistry 276 (17): 14092–9. doi:10.1074/jbc.M008902200. PMID 11278447. 
  17. ^ Karoor V, Wang L, Wang H, Malbon C (Dec 1998). "Insulin stimulates sequestration of beta-adrenergic receptors and enhanced association of beta-adrenergic receptors with Grb2 via tyrosine 350". The Journal of Biological Chemistry 273 (49): 33035–41. doi:10.1074/jbc.273.49.33035. PMID 9830057. 
  18. ^ Temkin P, Lauffer B, Jäger S, Cimermancic P, Krogan N, von Zastrow M (Jun 2011). "SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors". Nature Cell Biology 13 (6): 715–21. doi:10.1038/ncb2252. PMC 3113693. PMID 21602791. 
  19. ^ Karthikeyan S, Leung T, Ladias J (May 2002). "Structural determinants of the Na+/H+ exchanger regulatory factor interaction with the beta 2 adrenergic and platelet-derived growth factor receptors". The Journal of Biological Chemistry 277 (21): 18973–8. doi:10.1074/jbc.M201507200. PMID 11882663. 
  20. ^ Hall R, Ostedgaard L, Premont R, Blitzer J, Rahman N, Welsh M et al. (Jul 1998). "A C-terminal motif found in the beta2-adrenergic receptor, P2Y1 receptor and cystic fibrosis transmembrane conductance regulator determines binding to the Na+/H+ exchanger regulatory factor family of PDZ proteins". Proceedings of the National Academy of Sciences of the United States of America 95 (15): 8496–501. doi:10.1073/pnas.95.15.8496. PMC 21104. PMID 9671706. 
  21. ^ Hall R, Premont R, Chow C, Blitzer J, Pitcher J, Claing A et al. (Apr 1998). "The beta2-adrenergic receptor interacts with the Na+/H+-exchanger regulatory factor to control Na+/H+ exchange". Nature 392 (6676): 626–30. doi:10.1038/33458. PMID 9560162. 

Further reading[edit]

External links[edit]

  • 2-adrenoceptor". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.