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14-September-2008 12:50:34 - Beta-2 adrenergic receptor Redirected from ADRB2 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.12 Identifiers Symbols ADRB2; ADRB2R; ADRBR; B2AR; BAR; BETA2AR External IDs OMIM: 109690 MGI: 87938 HomoloGene: 30948 Gene ontology Molecular function: rhodopsin-like receptor activity receptor activity beta2-adrenergic receptor activity protein binding protein homodimerization activity norepinephrine binding Cellular component: membrane fraction nucleus lysosome endosome plasma membrane integral to plasma membrane apical plasma membrane receptor complex Biological process: activation of MAPK activity diet induced thermogenesis norepinephrine-epinephrine vasodilation during regulation of blood pressure regulation of sodium ion transport arrestin mediated desensitization of G-protein coupled receptor protein signaling pathway receptor-mediated endocytosis transmembrane receptor protein tyrosine kinase activation dimerization G-protein coupled receptor protein signaling pathway adenylate cyclase activation protein kinase cascade endosome to lysosome transport response to cold positive regulation of bone mineralization heat generation negative regulation of body size positive regulation of MAPKKK cascade bone resorption positive regulation of transcription from RNA polymerase II promoter negative regulation of smooth muscle contraction brown fat cell differentiation RNA expression pattern More reference expression data Orthologs Human Mouse Entrez 154 11555 Ensembl ENSG00000169252 ENSMUSG00000045730 Uniprot P07550 Q8BH38 Refseq NM_000024 mRNA NP_000015 protein NM_007420 mRNA NP_031446 protein Location Chr 5: 148.19 - 148.19 Mb Chr 18: 62.3 - 62.31 Mb Pubmed search 1 2 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 Contents 1 Gene 2 Structure 3 Mechanism 4 Function 4.1 Muscular system 4.2 Circulatory system 4.3 Digestive system 4.4 Other 5 Agonists 6 Antagonists 7 See also 8 References 9 Further reading 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, 2RH1.512 Mechanism This receptor is directly associated with one of its ultimate effectors, the class C L-type calcium channel CaV1.2. This receptor-channel complex also contains a G protein - Gs, 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 wall7 This effect is stronger than the alpha-1 receptor effect of contraction. Delay need of micturition seminal tract8 bronchi9 Facilitate respiration agonists can be useful in treating asthma blood vessels dilates smaller coronary arteries10 dilates hepatic artery arteries to skeletal muscle Increase perfusion of organs needed during fight-or-flight striated muscle Tremor8 Increased mass and contraction speed8 fight-or-flight glycogenolysis8 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 automaticity9 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.911 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 clenbuterol ritodrine tocolytic Antagonists Beta blockers butoxamine8 propranolol antihypertensive denotes selective agonists to the receptor. See also Other adrenergic receptors Alpha-1 adrenergic receptor Alpha-2 adrenergic receptor Beta-1 adrenergic receptor Beta-3 adrenergic receptor References ^ a b 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. ^ 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 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. 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. ^ a b c d e Rang, H. P. 2003. Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 163 ^ a b c d e f g Fitzpatrick, David; Purves, Dale; Augustine, George 2004. Table 20:2, Neuroscience, Third ion, 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. Further reading 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 beta2-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. This transmembrane receptor-related article is a stub. v d e Transmembrane receptor: G protein-coupled receptors Class A: Rhodopsin like Adrenergic α1 A, B, D, α2 A, B, C, β1, β2, β3 Eicosanoid CysLT 1, 2, LTB4 1, 2, FPRL1, OXE, Prostaglandin DP, EP 1, 2, 3, 4, PGF, Prostacyclin, Thromboxane Neuropeptide B/W 1, 2, FF 1, 2, S, Y 1, 2, 4, 5 Orphan GPR 1, 3, 4, 6, 12, 15, 17, 18, 19, 20, 21, 22, 23, 25, 26, 27, 31, 32, 33, 34, 35, 37, 39, 42, 44, 45, 50, 52, 55, 61, 62, 63, 65, 68, 75, 77, 78, 79, 82, 83, 84, 85, 87, 88, 92, 101, 103, 119, 120, 132, 135, 139, 141, 142, 146, 148, 149, 150, 151, 152, 153, 160, 161, 162, 171, 172, 173, 174, 176, 177, 182 Purinergics Adenosine A1, A2a, A2b, A3, P2Y, 1, 2, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14 Serotonin all but 5-HT3 5-HT1 A, B, D, E, F, 5-HT2 A, B, C, 5-HT 4, 5A, 6, 7 Other Acetylcholine M1, M2, M3, M4, M5 - Adrenomedullin - Anaphylatoxin C3a, C5a - Angiotensin 1, 2 - Apelin - Bile acid - Bombesin BRS3, GRPR, NMBR - Bradykinin B1, B2 - Cannabinoid CB1, CB2 - Chemokine - Cholecystokinin A, B - Dopamine D1, D2, D3, D4, D5 - EBI2 - Endothelin A, B - Estrogen - Formyl peptide 1, L1, L2 - Free fatty acid 1, 2, 3, 4 - FSH - Galanin 1, 2, 3 - Gonadotropin-releasing hormone 1, 2 - Ghrelin - Histamine H1, H2, H3, H4 - Kisspeptin - Luteinizing hormone/choriogonadotropin - Lysophospholipid 1, 2, 3, 4, 5, 6, 7, 8 - MAS 1, 1L, D, E, F, G, X1, X2, X3, X4 - Melanocortin 1, 2, 3, 4, 5 - MCHR 1, 2 - Melatonin 1A, 1B- Motilin - neuromedin B, U 1, 2 - Neurotensin 1, 2 - Opioid Delta, Kappa, Mu, Nociceptin, but not Sigma - Olfactory - Opsin 3, 4, 5, 1LW, 1MW, 1SW, RGR, RRH - Orexin 1, 2 - Oxytocin - Oxoglutarate - PAF - Prokineticin 1, 2 - Prolactin-releasing peptide - Protease-activated 1, 2, 3, 4 - Relaxin 1, 2, 3, 4 - Somatostatin 1, 2, 3, 4, 5 - SREB - Succinate - TAAR 1, 2, 3, 5, 6, 8, 9 - Tachykinin 1, 2, 3 - Thyrotropin - Thyrotropin-releasing hormone - Urotensin-II - Vasopressin 1A, 1B, 2 Class B: Secretin like Brain-specific angiogenesis inhibitor 1, 2, 3 - Cadherin 1, 2, 3 - Calcitonin - CD97 - Corticotropin-releasing hormone 1, 2 - EMR 1, 2, 3 - Glucagon GR, GIPR, GLP1R, GLP2R - Growth hormone releasing hormone - PACAPR1- GPR 56, 64, 97, 98, 110, 111, 112, 113, 114, 115, 116, 123, 124, 125, 126, 128, 133, 143, 144, 157 - Latrophilin 1, 2, 3, ELTD1 - Parathyroid hormone 1, 2 - Secretin - Vasoactive intestinal peptide 1, 2 Class C: Metabotropic glutamate / pheromone Calcium-sensing receptor - GABA B 1, 2 - Glutamate receptor Metabotropic glutamate 1, 2, 3, 4, 5, 6, 7, 8 - GPRC6A - GPR 156, 158, 179 - RAIG 1, 2, 3, 4 - Taste receptors TAS1R 1, 2, 3 TAS2R 1, 3, 4, 5, 8, 9, 10, 12, 13, 14, 16, 38, 39, 40, 41, 43, 44, 45, 46, 47, 48, 49, 50 Frizzled / Smoothened Frizzled 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 - Smoothened Retrieved from http://en..org/wiki/Beta-2_adrenergic_receptor Categories: Genes on chromosome 5 | Human proteins | Transmembrane receptor stubs | Adrenergic receptors | G protein coupled receptors Views Article Discussion this page History Personal tools Log in / create account Navigation Main page Contents Featured content Current events Random article Search Go Search Interaction Community portal Recent changes Contact Donate to Help Toolbox What links here Related changes Upload file Special pages Printable version Permanent link Cite this page Languages Español This page was last modified on 8 July 2008, at 02:25
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