Beta-2 adrenergic receptor

Adrenergic, beta-2-, receptor, surface
	Crystallographic structure of the human β2-adrenergic G-protein coupled receptor (PDB: 2RH1) depicted as a green cartoon structure 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).
Identifiers
Symbols	ADRB2 ; ADRB2R; ADRBR; B2AR; BAR; BETA2AR
External IDs	Template:OMIM5 Template:MGI HomoloGene: 30948
Gene ontology
Molecular function	Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO
Cellular component	Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO
Biological process	Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO
RNA expression pattern
	More reference expression data
Orthologs
	Template:GNF Ortholog box

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The beta-2 adrenergic receptor (β₂ adrenoreceptor), also known as ADRB2, is an beta-adrenergic receptor, and also denotes the human gene encoding it.^[3]

Gene

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]

Structure

The 3D crystallographic structure (see figure to the right) of the β₂-adrenergic receptor has been determined (PDB: 2R4R, 2R4S, 2RH1).^[5]^[1]^[2]

Mechanism

This receptor is directly associated with one of its ultimate effectors, the class C L-type calcium channel Ca_V1.2. This receptor-channel complex also contains a G protein - G_s, which activate an adenylyl cyclase, cAMP-dependent kinase, and the counterbalancing phosphatase, PP2A. The assembly of the signaling complex provides a mechanism that ensures specific and rapid signaling by this G protein-coupled receptor. A two-state biophysical and molecular model has been proposed to account for the pH and REDOX sensitivity of this and other GPCRs.^[6]

Function

Actions of the β₂ receptor include:

Muscular system

Effect		Function
Smooth muscle relaxation in:	uterus
	GI tract (decreases motility)	Delay digestion during fight-or-flight response
	detrusor urinae muscle‎ of bladder wall^[7] This effect is stronger than the alpha-1 receptor effect of contraction.	Delay need of micturition
	seminal tract^[8]
	bronchi^[9]	Facilitate respiration (agonists can be useful in treating asthma)
blood vessels dilates smaller coronary arteries^[10] dilates hepatic artery arteries to skeletal muscle	Increase perfusion of organs needed during fight-or-flight
striated muscle	Tremor^[8]
	Increased mass and contraction speed^[8]	fight-or-flight
	glycogenolysis^[8]	provide glucose fuel

Circulatory system

Increase cardiac output (minor degree compared to β₁).
- Increase heart rate ^[9] in sinoatrial node (SA node) (chronotropic effect).
- Increase atrial cardiac muscle contractility. (inotropic effect).
- Increases contractility and automaticity^[9] of ventricular cardiac muscle.
Dilate hepatic artery.
Dilate arteries to skeletal muscle.

Digestive system

Glycogenolysis and gluconeogenesis in liver.^[9]
Glycogenolysis and lactate release in skeletal muscle.^[9]
Contract sphincters of GI tract.
Insulin secretion from pancreas.^[9]^[11]
Thickened secretions from salivary glands.^[9]

Other

Inhibit histamine-release from mast cells.
Increase protein content of secretions from lacrimal glands.
Increase renin secretion from kidney.
Receptor also present in cerebellum.

Agonists

(Short/long)

spasmolytics in asthma and COPD
- salbutamol (albuterol in USA)
- bitolterol mesylate
- isoproterenol
- levalbuterol
- metaproterenol
- salmeterol
- terbutaline
ritodrine (tocolytic)

Antagonists

(Beta blockers)

* denotes selective agonists to the receptor.

Related Chapters

Other adrenergic receptors

References

↑ ^1.0 ^1.1 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 β₂-adrenergic G protein-coupled receptor". Science. 318 (5854): 1258–65. doi:10.1126/science.1150577. PMID 17962520.
↑ ^2.0 ^2.1 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 β₂-adrenergic receptor function". Science. 318 (5854): 1266–73. doi:10.1126/science.1150609. PMID 17962519.
↑ "Entrez Gene: ADRB1 adrenergic, beta-1-, receptor".
↑ "Entrez Gene: ADRB2 adrenergic, beta-2-, receptor, surface".
↑ Rasmussen SG, Choi HJ, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, Burghammer M, Ratnala VR, Sanishvili R, Fischetti RF, Schertler GF, Weis WI, Kobilka BK (2007). "Crystal structure of the human β₂-adrenergic G-protein-coupled receptor". Nature. 450 (7168): 383–7. doi:10.1038/nature06325. PMID 17952055.
↑ Rubenstein LA, Zauhar RJ, Lanzara RG (2006). "Molecular dynamics of a biophysical model for β₂-adrenergic and G protein-coupled receptor activation" (PDF). J. Mol. Graph. Model. 25 (4): 396–409. doi:10.1016/j.jmgm.2006.02.008. PMID 16574446.
↑ von Heyden B, Riemer RK, Nunes L, Brock GB, Lue TF, Tanagho EA (1995). "Response of guinea pig smooth and striated urethral sphincter to cromakalim, prazosin, nifedipine, nitroprusside, and electrical stimulation". Neurourol. Urodyn. 14 (2): 153–68. doi:10.1002/nau.1930140208. PMID 7540086.
↑ ^8.0 ^8.1 ^8.2 ^8.3 ^8.4 Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 163
↑ ^9.0 ^9.1 ^9.2 ^9.3 ^9.4 ^9.5 ^9.6 Fitzpatrick, David; Purves, Dale; Augustine, George (2004). "Table 20:2". Neuroscience (Third Edition ed.). Sunderland, Mass: Sinauer. ISBN 0-87893-725-0.
↑ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 270
↑ Trovik TS, Vaartun A, Jorde R, Sager G (1995). "Dysfunction in the beta 2-adrenergic signal pathway in patients with insulin dependent diabetes mellitus (IDDM) and unawareness of hypoglycaemia". Eur. J. Clin. Pharmacol. 48 (5): 327–32. PMID 8641318.

Frielle T, Caron MG, Lefkowitz RJ (1989). "Properties of the beta 1- and beta 2-adrenergic receptor subtypes revealed by molecular cloning". Clin. Chem. 35 (5): 721–5. PMID 2541947.
Taylor DR, Kennedy MA (2002). "Genetic variation of the beta(2)-adrenoceptor: its functional and clinical importance in bronchial asthma". American journal of pharmacogenomics : genomics-related research in drug development and clinical practice. 1 (3): 165–74. PMID 12083965.
Thibonnier M, Coles P, Thibonnier A, Shoham M (2002). "Molecular pharmacology and modeling of vasopressin receptors". Prog. Brain Res. 139: 179–96. PMID 12436935.
Ge D, Huang J, He J; et al. (2005). "beta2-Adrenergic receptor gene variations associated with stage-2 hypertension in northern Han Chinese". Ann. Hum. Genet. 69 (Pt 1): 36–44. doi:10.1046/j.1529-8817.2003.00093.x. PMID 15638826.
Muszkat M (2007). "Interethnic differences in drug response: the contribution of genetic variability in beta adrenergic receptor and cytochrome P4502C9". Clin. Pharmacol. Ther. 82 (2): 215–8. doi:10.1038/sj.clpt.6100142. PMID 17329986.
Bucens D, Pain MC (1976). "Influence of hematocrit, blood gas tensions, and pH on pressure-flow relations in the isolated canine lung". Circ. Res. 37 (5): 588–96. PMID 154.
von Zastrow M, Kobilka BK (1992). "Ligand-regulated internalization and recycling of human beta 2-adrenergic receptors between the plasma membrane and endosomes containing transferrin receptors". J. Biol. Chem. 267 (5): 3530–8. PMID 1371121.
Gope R, Gope ML, Thorson A; et al. (1992). "Genetic changes at the beta-2-adrenergic receptor locus on chromosome 5 in human colorectal carcinomas". Anticancer Res. 11 (6): 2047–50. PMID 1663718.
Bouvier M, Guilbault N, Bonin H (1991). "Phorbol-ester-induced phosphorylation of the beta 2-adrenergic receptor decreases its coupling to Gs". FEBS Lett. 279 (2): 243–8. PMID 1848190.
Yang-Feng TL, Xue FY, Zhong WW; et al. (1990). "Chromosomal organization of adrenergic receptor genes". Proc. Natl. Acad. Sci. U.S.A. 87 (4): 1516–20. PMID 2154750.
Hui KK, Yu JL (1989). "Effects of protein kinase inhibitor, 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine, on beta-2 adrenergic receptor activation and desensitization in intact human lymphocytes". J. Pharmacol. Exp. Ther. 249 (2): 492–8. PMID 2470898.
Hen R, Axel R, Obici S (1989). "Activation of the beta 2-adrenergic receptor promotes growth and differentiation in thyroid cells". Proc. Natl. Acad. Sci. U.S.A. 86 (12): 4785–8. PMID 2471981.
O'Dowd BF, Hnatowich M, Caron MG; et al. (1989). "Palmitoylation of the human beta 2-adrenergic receptor. Mutation of Cys341 in the carboxyl tail leads to an uncoupled nonpalmitoylated form of the receptor". J. Biol. Chem. 264 (13): 7564–9. PMID 2540197.
Bristow MR, Hershberger RE, Port JD; et al. (1989). "Beta 1- and beta 2-adrenergic receptor-mediated adenylate cyclase stimulation in nonfailing and failing human ventricular myocardium". Mol. Pharmacol. 35 (3): 295–303. PMID 2564629.
Emorine LJ, Marullo S, Delavier-Klutchko C; et al. (1987). "Structure of the gene for human beta 2-adrenergic receptor: expression and promoter characterization". Proc. Natl. Acad. Sci. U.S.A. 84 (20): 6995–9. PMID 2823249.
Chung FZ, Wang CD, Potter PC; et al. (1988). "Site-directed mutagenesis and continuous expression of human beta-adrenergic receptors. Identification of a conserved aspartate residue involved in agonist binding and receptor activation". J. Biol. Chem. 263 (9): 4052–5. PMID 2831218.
Yang SD, Fong YL, Benovic JL; et al. (1988). "Dephosphorylation of the beta 2-adrenergic receptor and rhodopsin by latent phosphatase 2". J. Biol. Chem. 263 (18): 8856–8. PMID 2837466.
Kobilka BK, Dixon RA, Frielle T; et al. (1987). "cDNA for the human beta 2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for platelet-derived growth factor". Proc. Natl. Acad. Sci. U.S.A. 84 (1): 46–50. PMID 3025863.
Chung FZ, Lentes KU, Gocayne J; et al. (1987). "Cloning and sequence analysis of the human brain beta-adrenergic receptor. Evolutionary relationship to rodent and avian beta-receptors and porcine muscarinic receptors". FEBS Lett. 211 (2): 200–6. PMID 3026848.

Stub icon

This membrane protein–related article is a stub. You can help Wikipedia by expanding it.

Template:WH Template:WS

[Cherezov_2007-1] 1.0 ^1.1 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 β₂-adrenergic G protein-coupled receptor". Science. 318 (5854): 1258–65. doi:10.1126/science.1150577. PMID 17962520.

[Rosenbaum_2007-2] 2.0 ^2.1 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 β₂-adrenergic receptor function". Science. 318 (5854): 1266–73. doi:10.1126/science.1150609. PMID 17962519.

[entrez-3] "Entrez Gene: ADRB1 adrenergic, beta-1-, receptor".

[4] "Entrez Gene: ADRB2 adrenergic, beta-2-, receptor, surface".

[Rasmussen_2007-5] Rasmussen SG, Choi HJ, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, Burghammer M, Ratnala VR, Sanishvili R, Fischetti RF, Schertler GF, Weis WI, Kobilka BK (2007). "Crystal structure of the human β₂-adrenergic G-protein-coupled receptor". Nature. 450 (7168): 383–7. doi:10.1038/nature06325. PMID 17952055.

[pmid16574446-6] Rubenstein LA, Zauhar RJ, Lanzara RG (2006). "Molecular dynamics of a biophysical model for β₂-adrenergic and G protein-coupled receptor activation" (PDF). J. Mol. Graph. Model. 25 (4): 396–409. doi:10.1016/j.jmgm.2006.02.008. PMID 16574446.

[pmid7540086-7] von Heyden B, Riemer RK, Nunes L, Brock GB, Lue TF, Tanagho EA (1995). "Response of guinea pig smooth and striated urethral sphincter to cromakalim, prazosin, nifedipine, nitroprusside, and electrical stimulation". Neurourol. Urodyn. 14 (2): 153–68. doi:10.1002/nau.1930140208. PMID 7540086.

[Rang163-8] 8.0 ^8.1 ^8.2 ^8.3 ^8.4 Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 163

[purves-9] 9.0 ^9.1 ^9.2 ^9.3 ^9.4 ^9.5 ^9.6 Fitzpatrick, David; Purves, Dale; Augustine, George (2004). "Table 20:2". Neuroscience (Third Edition ed.). Sunderland, Mass: Sinauer. ISBN 0-87893-725-0.

[Rang270-10] Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 270

[pmid8641318-11] Trovik TS, Vaartun A, Jorde R, Sager G (1995). "Dysfunction in the beta 2-adrenergic signal pathway in patients with insulin dependent diabetes mellitus (IDDM) and unawareness of hypoglycaemia". Eur. J. Clin. Pharmacol. 48 (5): 327–32. PMID 8641318.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

[9]

[10]

[11]