α2-adrenergic receptors include 3 highly homologous subtypes: α2A, α2B, and α2C. These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system.
A deletion variant of the α2B adrenergic receptor has been shown to be related to emotional memory in Europeans and Africans.[7] This variant also predisposed people who had it to focus more on negative aspects of a situation.[8] This predisposition remained present in people with the variant gene who took a single dose of the noradrenergic antidepressant reboxetine, but was weakened in people without the variant.[9]
Evolution
The ADRA2B gene (sometimes referenced as A2AB) is used in animals as a nuclear DNA phylogenetic marker.[6] This intronless gene has first been used to explore the phylogeny of the major groups of mammals,[10] and contributed to reveal that placental orders are distributed into four major clades: Xenarthra, Afrotheria, Laurasiatheria, and Euarchontoglires. Comparative analysis of the primary protein sequence of ADRA2B across placentals also showed the high conservation of residues thought to be involved in agonist binding and in G protein–coupling. However, great variations are observed in the very long, third intracellular loop, with a polyglutamyl domain displaying pervasive length differences.[11]
Research
A paper published on 28 June 2022 demonstrated that ADRA2B may be one of the potential targets of ALS. It is found that ADRA2B is upregulated in CNS transcriptomic fALS using an AI-enabled biological target discovery platform. With target discovery, several pathways and drugs can be further designed to treat ALS.[12]
^de Quervain DJ, Kolassa IT, Ertl V, Onyut PL, Neuner F, Elbert T, Papassotiropoulos A (Sep 2007). "A deletion variant of the alpha2b-adrenoceptor is related to emotional memory in Europeans and Africans". Nature Neuroscience. 10 (9): 1137–9. doi:10.1038/nn1945. PMID 17660814. S2CID 899166.
^Todd RM, Müller DJ, Lee DH, Robertson A, Eaton T, Freeman N, Palombo DJ, Levine B, Anderson AK (2013). "Genes for emotion-enhanced remembering are linked to enhanced perceiving". Psychol Sci. 24 (11): 2244–53. doi:10.1177/0956797613492423. PMID 24058067. S2CID 9603198.
Lay summary in: "Genes predispose some people to focus on the negative". The University of British Columbia. October 10, 2013.
^Gibbs AA, Bautista CE, Mowlem FD, Naudts KH, Duka T (2013). "Alpha 2B adrenoceptor genotype moderates effect of reboxetine on negative emotional memory bias in healthy volunteers". J. Neurosci. 33 (43): 17023–8. doi:10.1523/JNEUROSCI.2124-13.2013. PMC6618435. PMID 24155306.
Lay summary in: . Society for Neuroscience (Press release). 2013-10-22. Archived from the original on 2013-10-24.
^Madsen O, Scally M, Douady CJ, Kao DJ, DeBry RW, Adkins R, Amrine HM, Stanhope MJ, de Jong WW, Springer MS (Feb 2001). "Parallel adaptive radiations in two major clades of placental mammals". Nature. 409 (6820): 610–4. Bibcode:2001Natur.409..610M. doi:10.1038/35054544. PMID 11214318. S2CID 4398233.
^Madsen O, Willemsen D, Ursing BM, Arnason U, de Jong WW (Dec 2002). "Molecular evolution of the mammalian alpha 2B adrenergic receptor". Molecular Biology and Evolution. 19 (12): 2150–60. doi:10.1093/oxfordjournals.molbev.a004040. PMID 12446807.
^Pun, Frank W.; Liu, Bonnie Hei Man; Long, Xi; Leung, Hoi Wing; Leung, Geoffrey Ho Duen; Mewborne, Quinlan T.; Gao, Junli; Shneyderman, Anastasia; Ozerov, Ivan V.; Wang, Ju; Ren, Feng (2022). "Identification of Therapeutic Targets for Amyotrophic Lateral Sclerosis Using PandaOmics – An AI-Enabled Biological Target Discovery Platform". Frontiers in Aging Neuroscience. 14: 914017. doi:10.3389/fnagi.2022.914017. ISSN 1663-4365. PMC9273868. PMID 35837482.
^Davis RA, Fechner GA, Sykes M, Garavelas A, Pass DM, Carroll AR, Addepalli R, Avery VM, Hooper JN, Quinn RJ (Mar 2009). "(-)-Dibromophakellin: an alpha2B adrenoceptor agonist isolated from the Australian marine sponge, Acanthella costata". Bioorganic & Medicinal Chemistry. 17 (6): 2497–500. doi:10.1016/j.bmc.2009.01.065. hdl:10072/28568. PMID 19243956.
External links
Human ADRA2B genome location and ADRA2B gene details page in the UCSC Genome Browser.
Further reading
Lomasney JW, Lorenz W, Allen LF, King K, Regan JW, Yang-Feng TL, Caron MG, Lefkowitz RJ (Jul 1990). "Expansion of the alpha 2-adrenergic receptor family: cloning and characterization of a human alpha 2-adrenergic receptor subtype, the gene for which is located on chromosome 2". Proceedings of the National Academy of Sciences of the United States of America. 87 (13): 5094–8. Bibcode:1990PNAS...87.5094L. doi:10.1073/pnas.87.13.5094. PMC54268. PMID 2164221.
McClue SJ, Milligan G (Sep 1990). "The alpha 2B adrenergic receptor of undifferentiated neuroblastoma x glioma hybrid NG108-15 cells, interacts directly with the guanine nucleotide binding protein, Gi2". FEBS Letters. 269 (2): 430–4. doi:10.1016/0014-5793(90)81209-7. PMID 2169434. S2CID 24246875.
Weinshank RL, Zgombick JM, Macchi M, Adham N, Lichtblau H, Branchek TA, Hartig PR (Nov 1990). "Cloning, expression, and pharmacological characterization of a human alpha 2B-adrenergic receptor". Molecular Pharmacology. 38 (5): 681–8. PMID 2172775.
Chang AC, Ho TF, Chang NC (Oct 1990). "In vitro amplification by polymerase chain reaction of a partial gene encoding the third subtype of alpha-2 adrenergic receptor in humans". Biochemical and Biophysical Research Communications. 172 (2): 817–23. doi:10.1016/0006-291X(90)90748-C. PMID 2173582.
Regan JW, Kobilka TS, Yang-Feng TL, Caron MG, Lefkowitz RJ, Kobilka BK (Sep 1988). "Cloning and expression of a human kidney cDNA for an alpha 2-adrenergic receptor subtype". Proceedings of the National Academy of Sciences of the United States of America. 85 (17): 6301–5. Bibcode:1988PNAS...85.6301R. doi:10.1073/pnas.85.17.6301. PMC281957. PMID 2842764.
Petrash AC, Bylund DB (Jun 1986). "Alpha-2 adrenergic receptor subtypes indicated by [3H]yohimbine binding in human brain". Life Sciences. 38 (23): 2129–37. doi:10.1016/0024-3205(86)90212-2. PMID 3012234.
Klein U, Ramirez MT, Kobilka BK, von Zastrow M (Aug 1997). "A novel interaction between adrenergic receptors and the alpha-subunit of eukaryotic initiation factor 2B". The Journal of Biological Chemistry. 272 (31): 19099–102. doi:10.1074/jbc.272.31.19099. PMID 9235896.
Okusa MD, Huang L, Momose-Hotokezaka A, Huynh LP, Mangrum AJ (Dec 1997). "Regulation of adenylyl cyclase in polarized renal epithelial cells by G protein-coupled receptors". The American Journal of Physiology. 273 (6 Pt 2): F883–91. doi:10.1152/ajprenal.1997.273.6.F883. PMID 9435676.
Prezeau L, Richman JG, Edwards SW, Limbird LE (May 1999). "The zeta isoform of 14-3-3 proteins interacts with the third intracellular loop of different alpha2-adrenergic receptor subtypes". The Journal of Biological Chemistry. 274 (19): 13462–9. doi:10.1074/jbc.274.19.13462. PMID 10224112.
Heinonen P, Koulu M, Pesonen U, Karvonen MK, Rissanen A, Laakso M, Valve R, Uusitupa M, Scheinin M (Jul 1999). "Identification of a three-amino acid deletion in the alpha2B-adrenergic receptor that is associated with reduced basal metabolic rate in obese subjects". The Journal of Clinical Endocrinology and Metabolism. 84 (7): 2429–33. doi:10.1210/jcem.84.7.5818. PMID 10404816.
Small KM, Brown KM, Forbes SL, Liggett SB (Feb 2001). "Polymorphic deletion of three intracellular acidic residues of the alpha 2B-adrenergic receptor decreases G protein-coupled receptor kinase-mediated phosphorylation and desensitization". The Journal of Biological Chemistry. 276 (7): 4917–22. doi:10.1074/jbc.M008118200. PMID 11056163.
Snapir A, Mikkelsson J, Perola M, Penttilä A, Scheinin M, Karhunen PJ (Jan 2003). "Variation in the alpha2B-adrenoceptor gene as a risk factor for prehospital fatal myocardial infarction and sudden cardiac death". Journal of the American College of Cardiology. 41 (2): 190–4. doi:10.1016/S0735-1097(02)02702-X. PMID 12535806.
Chotani MA, Mitra S, Su BY, Flavahan S, Eid AH, Clark KR, Montague CR, Paris H, Handy DE, Flavahan NA (Jan 2004). "Regulation of alpha(2)-adrenoceptors in human vascular smooth muscle cells". American Journal of Physiology. Heart and Circulatory Physiology. 286 (1): H59–67. doi:10.1152/ajpheart.00268.2003. PMID 12946937.
Von Wowern F, Bengtsson K, Lindblad U, Råstam L, Melander O (Mar 2004). "Functional variant in the (alpha)2B adrenoceptor gene, a positional candidate on chromosome 2, associates with hypertension". Hypertension. 43 (3): 592–7. doi:10.1161/01.HYP.0000116224.51189.80. PMID 14744925.
Cayla C, Heinonen P, Viikari L, Schaak S, Snapir A, Bouloumié A, Karvonen MK, Pesonen U, Scheinin M, Paris H (Feb 2004). "Cloning, characterisation and identification of several polymorphisms in the promoter region of the human alpha2B-adrenergic receptor gene". Biochemical Pharmacology. 67 (3): 469–78. doi:10.1016/j.bcp.2003.09.029. PMID 15037199.
Phares DA, Halverstadt AA, Shuldiner AR, Ferrell RE, Douglass LW, Ryan AS, Goldberg AP, Hagberg JM (May 2004). "Association between body fat response to exercise training and multilocus ADR genotypes". Obesity Research. 12 (5): 807–15. doi:10.1038/oby.2004.97. PMID 15166301.
Siitonen N, Lindström J, Eriksson J, Valle TT, Hämäläinen H, Ilanne-Parikka P, Keinänen-Kiukaanniemi S, Tuomilehto J, Laakso M, Uusitupa M (Aug 2004). "Association between a deletion/insertion polymorphism in the alpha2B-adrenergic receptor gene and insulin secretion and Type 2 diabetes. The Finnish Diabetes Prevention Study". Diabetologia. 47 (8): 1416–24. doi:10.1007/s00125-004-1462-z. PMID 15309292.
Belfer I, Buzas B, Hipp H, Phillips G, Taubman J, Lorincz I, Evans C, Lipsky RH, Enoch MA, Max MB, Goldman D (2005). "Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene". Journal of Human Genetics. 50 (1): 12–20. doi:10.1007/s10038-004-0211-y. PMID 15592690.
January 08, 2023
alpha, adrenergic, receptor, alpha, adrenergic, receptor, α2b, adrenoceptor, protein, coupled, receptor, subtype, adrenergic, receptor, family, human, gene, encoding, this, receptor, symbol, adra2b, adra2b, orthologs, have, been, identified, several, mammals, . The alpha 2B adrenergic receptor a2B adrenoceptor is a G protein coupled receptor It is a subtype of the adrenergic receptor family The human gene encoding this receptor has the symbol ADRA2B 5 ADRA2B orthologs 6 have been identified in several mammals ADRA2BAvailable structuresPDBOrtholog search PDBe RCSBList of PDB id codes2CVAIdentifiersAliasesADRA2B ADRA2L1 ADRA2RL1 ADRARL1 ALPHA2BAR alpha 2BAR FAME2 adrenoceptor alpha 2BExternal IDsOMIM 104260 MGI 87935 HomoloGene 553 GeneCards ADRA2BGene location Human Chr Chromosome 2 human 1 Band2q11 2Start96 112 876 bp 1 End96 116 571 bp 1 Gene location Mouse Chr Chromosome 2 mouse 2 Band2 F1 2 61 95 cMStart127 205 128 bp 2 End127 209 141 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed ingastrocnemius muscleleft ventricleright lobe of liverspleensubcutaneous adipose tissuetibial nerveascending aortagastric mucosatendonpopliteal arteryTop expressed inproximal tubulekidneyyolk sachepatobiliary systemliversecondary oocyteendocardial cushionlateral geniculate nucleusmedial dorsal nucleusmedial geniculate nucleusMore reference expression dataBioGPSn aGene ontologyMolecular functionG protein coupled receptor activity signal transducer activity alpha2 adrenergic receptor activity adrenergic receptor activity epinephrine binding protein bindingCellular componentintegral component of membrane plasma membrane membrane integral component of plasma membrane intracellular anatomical structure cell surfaceBiological processplatelet activation female pregnancy G protein coupled receptor signaling pathway positive regulation of blood pressure adrenergic receptor signaling pathway regulation of vasoconstriction regulation of vascular associated smooth muscle contraction positive regulation of uterine smooth muscle contraction regulation of smooth muscle contraction signal transduction activation of protein kinase B activity negative regulation of epinephrine secretion cell cell signaling adenylate cyclase activating adrenergic receptor signaling pathway positive regulation of neuron differentiation negative regulation of norepinephrine secretion positive regulation of MAPK cascade receptor transactivation adenylate cyclase modulating G protein coupled receptor signaling pathwaySources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez15111552EnsemblENSG00000274286ENSMUSG00000058620UniProtP18089P30545RefSeq mRNA NM 000682NM 009633RefSeq protein NP 000673NP 033763Location UCSC Chr 2 96 11 96 12 MbChr 2 127 21 127 21 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Receptor 2 Clinical significance 3 Evolution 4 Research 5 Ligands 6 See also 7 References 8 External links 9 Further readingReceptor Edita2 adrenergic receptors include 3 highly homologous subtypes a2A a2B and a2C These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system Clinical significance EditThis gene encodes the a2B subtype which was observed to associate with eIF 2B a guanine nucleotide exchange protein that functions in regulation of translation A polymorphic variant of the a2B subtype which lacks 3 glutamic acids from a glutamic acid repeat element was identified to have decreased G protein coupled receptor kinase mediated phosphorylation and desensitization this polymorphic form is also associated with reduced basal metabolic rate in obese subjects and may therefore contribute to the pathogenesis of obesity This gene contains no introns in either its coding or untranslated sequences 5 A deletion variant of the a2B adrenergic receptor has been shown to be related to emotional memory in Europeans and Africans 7 This variant also predisposed people who had it to focus more on negative aspects of a situation 8 This predisposition remained present in people with the variant gene who took a single dose of the noradrenergic antidepressant reboxetine but was weakened in people without the variant 9 Evolution EditThe ADRA2B gene sometimes referenced as A2AB is used in animals as a nuclear DNA phylogenetic marker 6 This intronless gene has first been used to explore the phylogeny of the major groups of mammals 10 and contributed to reveal that placental orders are distributed into four major clades Xenarthra Afrotheria Laurasiatheria and Euarchontoglires Comparative analysis of the primary protein sequence of ADRA2B across placentals also showed the high conservation of residues thought to be involved in agonist binding and in G protein coupling However great variations are observed in the very long third intracellular loop with a polyglutamyl domain displaying pervasive length differences 11 Research EditA paper published on 28 June 2022 demonstrated that ADRA2B may be one of the potential targets of ALS It is found that ADRA2B is upregulated in CNS transcriptomic fALS using an AI enabled biological target discovery platform With target discovery several pathways and drugs can be further designed to treat ALS 12 Ligands EditAgonists Dibromophakellin 13 AntagonistsImiloxan YohimbineSee also EditAdrenergic receptorReferences Edit a b c GRCh38 Ensembl release 89 ENSG00000274286 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000058620 Ensembl May 2017 Human PubMed Reference National Center for Biotechnology Information U S National Library of Medicine Mouse PubMed Reference National Center for Biotechnology Information U S National Library of Medicine a b Entrez Gene ADRA2B adrenergic alpha 2B receptor a b OrthoMaM phylogenetic marker ADRA2B coding sequence permanent dead link de Quervain DJ Kolassa IT Ertl V Onyut PL Neuner F Elbert T Papassotiropoulos A Sep 2007 A deletion variant of the alpha2b adrenoceptor is related to emotional memory in Europeans and Africans Nature Neuroscience 10 9 1137 9 doi 10 1038 nn1945 PMID 17660814 S2CID 899166 Todd RM Muller DJ Lee DH Robertson A Eaton T Freeman N Palombo DJ Levine B Anderson AK 2013 Genes for emotion enhanced remembering are linked to enhanced perceiving Psychol Sci 24 11 2244 53 doi 10 1177 0956797613492423 PMID 24058067 S2CID 9603198 Lay summary in Genes predispose some people to focus on the negative The University of British Columbia October 10 2013 Gibbs AA Bautista CE Mowlem FD Naudts KH Duka T 2013 Alpha 2B adrenoceptor genotype moderates effect of reboxetine on negative emotional memory bias in healthy volunteers J Neurosci 33 43 17023 8 doi 10 1523 JNEUROSCI 2124 13 2013 PMC 6618435 PMID 24155306 Lay summary in Genetic variation alters efficacy of antidepressant Society for Neuroscience Press release 2013 10 22 Archived from the original on 2013 10 24 Madsen O Scally M Douady CJ Kao DJ DeBry RW Adkins R Amrine HM Stanhope MJ de Jong WW Springer MS Feb 2001 Parallel adaptive radiations in two major clades of placental mammals Nature 409 6820 610 4 Bibcode 2001Natur 409 610M doi 10 1038 35054544 PMID 11214318 S2CID 4398233 Madsen O Willemsen D Ursing BM Arnason U de Jong WW Dec 2002 Molecular evolution of the mammalian alpha 2B adrenergic receptor Molecular Biology and Evolution 19 12 2150 60 doi 10 1093 oxfordjournals molbev a004040 PMID 12446807 Pun Frank W Liu Bonnie Hei Man Long Xi Leung Hoi Wing Leung Geoffrey Ho Duen Mewborne Quinlan T Gao Junli Shneyderman Anastasia Ozerov Ivan V Wang Ju Ren Feng 2022 Identification of Therapeutic Targets for Amyotrophic Lateral Sclerosis Using PandaOmics An AI Enabled Biological Target Discovery Platform Frontiers in Aging Neuroscience 14 914017 doi 10 3389 fnagi 2022 914017 ISSN 1663 4365 PMC 9273868 PMID 35837482 Davis RA Fechner GA Sykes M Garavelas A Pass DM Carroll AR Addepalli R Avery VM Hooper JN Quinn RJ Mar 2009 Dibromophakellin an alpha2B adrenoceptor agonist isolated from the Australian marine sponge Acanthella costata Bioorganic amp Medicinal Chemistry 17 6 2497 500 doi 10 1016 j bmc 2009 01 065 hdl 10072 28568 PMID 19243956 External links EditHuman ADRA2B genome location and ADRA2B gene details page in the UCSC Genome Browser Further reading EditLomasney JW Lorenz W Allen LF King K Regan JW Yang Feng TL Caron MG Lefkowitz RJ Jul 1990 Expansion of the alpha 2 adrenergic receptor family cloning and characterization of a human alpha 2 adrenergic receptor subtype the gene for which is located on chromosome 2 Proceedings of the National Academy of Sciences of the United States of America 87 13 5094 8 Bibcode 1990PNAS 87 5094L doi 10 1073 pnas 87 13 5094 PMC 54268 PMID 2164221 McClue SJ Milligan G Sep 1990 The alpha 2B adrenergic receptor of undifferentiated neuroblastoma x glioma hybrid NG108 15 cells interacts directly with the guanine nucleotide binding protein Gi2 FEBS Letters 269 2 430 4 doi 10 1016 0014 5793 90 81209 7 PMID 2169434 S2CID 24246875 Weinshank RL Zgombick JM Macchi M Adham N Lichtblau H Branchek TA Hartig PR Nov 1990 Cloning expression and pharmacological characterization of a human alpha 2B adrenergic receptor Molecular Pharmacology 38 5 681 8 PMID 2172775 Chang AC Ho TF Chang NC Oct 1990 In vitro amplification by polymerase chain reaction of a partial gene encoding the third subtype of alpha 2 adrenergic receptor in humans Biochemical and Biophysical Research Communications 172 2 817 23 doi 10 1016 0006 291X 90 90748 C PMID 2173582 Regan JW Kobilka TS Yang Feng TL Caron MG Lefkowitz RJ Kobilka BK Sep 1988 Cloning and expression of a human kidney cDNA for an alpha 2 adrenergic receptor subtype Proceedings of the National Academy of Sciences of the United States of America 85 17 6301 5 Bibcode 1988PNAS 85 6301R doi 10 1073 pnas 85 17 6301 PMC 281957 PMID 2842764 Petrash AC Bylund DB Jun 1986 Alpha 2 adrenergic receptor subtypes indicated by 3H yohimbine binding in human brain Life Sciences 38 23 2129 37 doi 10 1016 0024 3205 86 90212 2 PMID 3012234 Klein U Ramirez MT Kobilka BK von Zastrow M Aug 1997 A novel interaction between adrenergic receptors and the alpha subunit of eukaryotic initiation factor 2B The Journal of Biological Chemistry 272 31 19099 102 doi 10 1074 jbc 272 31 19099 PMID 9235896 Okusa MD Huang L Momose Hotokezaka A Huynh LP Mangrum AJ Dec 1997 Regulation of adenylyl cyclase in polarized renal epithelial cells by G protein coupled receptors The American Journal of Physiology 273 6 Pt 2 F883 91 doi 10 1152 ajprenal 1997 273 6 F883 PMID 9435676 Prezeau L Richman JG Edwards SW Limbird LE May 1999 The zeta isoform of 14 3 3 proteins interacts with the third intracellular loop of different alpha2 adrenergic receptor subtypes The Journal of Biological Chemistry 274 19 13462 9 doi 10 1074 jbc 274 19 13462 PMID 10224112 Heinonen P Koulu M Pesonen U Karvonen MK Rissanen A Laakso M Valve R Uusitupa M Scheinin M Jul 1999 Identification of a three amino acid deletion in the alpha2B adrenergic receptor that is associated with reduced basal metabolic rate in obese subjects The Journal of Clinical Endocrinology and Metabolism 84 7 2429 33 doi 10 1210 jcem 84 7 5818 PMID 10404816 Hein L Altman JD Kobilka BK Nov 1999 Two functionally distinct alpha2 adrenergic receptors regulate sympathetic neurotransmission Nature 402 6758 181 4 Bibcode 1999Natur 402 181H doi 10 1038 46040 PMID 10647009 S2CID 205047992 Small KM Brown KM Forbes SL Liggett SB Feb 2001 Polymorphic deletion of three intracellular acidic residues of the alpha 2B adrenergic receptor decreases G protein coupled receptor kinase mediated phosphorylation and desensitization The Journal of Biological Chemistry 276 7 4917 22 doi 10 1074 jbc M008118200 PMID 11056163 Snapir A Mikkelsson J Perola M Penttila A Scheinin M Karhunen PJ Jan 2003 Variation in the alpha2B adrenoceptor gene as a risk factor for prehospital fatal myocardial infarction and sudden cardiac death Journal of the American College of Cardiology 41 2 190 4 doi 10 1016 S0735 1097 02 02702 X PMID 12535806 Sykiotis GP Polyzogopoulou E Georgopoulos NA Trakada G Spyropoulos K Kalfarentzos F Papavassiliou AG Vagenakis AG Flordellis CS Jun 2003 The alpha2B adrenergic receptor deletion insertion polymorphism in morbid obesity Clinical Autonomic Research 13 3 203 7 doi 10 1007 s10286 003 0087 5 PMID 12822042 S2CID 10913264 Chotani MA Mitra S Su BY Flavahan S Eid AH Clark KR Montague CR Paris H Handy DE Flavahan NA Jan 2004 Regulation of alpha 2 adrenoceptors in human vascular smooth muscle cells American Journal of Physiology Heart and Circulatory Physiology 286 1 H59 67 doi 10 1152 ajpheart 00268 2003 PMID 12946937 Von Wowern F Bengtsson K Lindblad U Rastam L Melander O Mar 2004 Functional variant in the alpha 2B adrenoceptor gene a positional candidate on chromosome 2 associates with hypertension Hypertension 43 3 592 7 doi 10 1161 01 HYP 0000116224 51189 80 PMID 14744925 Cayla C Heinonen P Viikari L Schaak S Snapir A Bouloumie A Karvonen MK Pesonen U Scheinin M Paris H Feb 2004 Cloning characterisation and identification of several polymorphisms in the promoter region of the human alpha2B adrenergic receptor gene Biochemical Pharmacology 67 3 469 78 doi 10 1016 j bcp 2003 09 029 PMID 15037199 Phares DA Halverstadt AA Shuldiner AR Ferrell RE Douglass LW Ryan AS Goldberg AP Hagberg JM May 2004 Association between body fat response to exercise training and multilocus ADR genotypes Obesity Research 12 5 807 15 doi 10 1038 oby 2004 97 PMID 15166301 Siitonen N Lindstrom J Eriksson J Valle TT Hamalainen H Ilanne Parikka P Keinanen Kiukaanniemi S Tuomilehto J Laakso M Uusitupa M Aug 2004 Association between a deletion insertion polymorphism in the alpha2B adrenergic receptor gene and insulin secretion and Type 2 diabetes The Finnish Diabetes Prevention Study Diabetologia 47 8 1416 24 doi 10 1007 s00125 004 1462 z PMID 15309292 Belfer I Buzas B Hipp H Phillips G Taubman J Lorincz I Evans C Lipsky RH Enoch MA Max MB Goldman D 2005 Haplotype based analysis of alpha 2A 2B and 2C adrenergic receptor genes captures information on common functional loci at each gene Journal of Human Genetics 50 1 12 20 doi 10 1007 s10038 004 0211 y PMID 15592690 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