The alpha-2C adrenergic receptor (α2C adrenoceptor), also known as ADRA2C, is an alpha-2 adrenergic receptor, and also denotes the human gene encoding it.[5]
Alpha-2-adrenergic receptors include 3 highly homologous subtypes: alpha2A, alpha2B, and alpha2C. These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system. Studies in mice revealed that both the alpha2A and alpha2C subtypes were required for normal presynaptic control of transmitter release from sympathetic nerves in the heart and from central noradrenergic neurons; the alpha2A subtype inhibited transmitter release at high stimulation frequencies, whereas the alpha2C subtype modulated neurotransmission at lower levels of nerve activity.[6]
^Crassous PA, Cardinaletti C, Carrieri A, Bruni B, Di Vaira M, Gentili F, Ghelfi F, Giannella M, Paris H, Piergentili A, Quaglia W, Schaak S, Vesprini C, Pigini M (August 2007). "Alpha2-adrenoreceptors profile modulation. 3.1 (R)-(+)-m-nitrobiphenyline, a new efficient and alpha2C-subtype selective agonist". Journal of Medicinal Chemistry. 50 (16): 3964–8. doi:10.1021/jm061487a. PMID 17630725.
^Cleary L, Murad K, Bexis S, Docherty JR (2005). "The alpha (1D)-adrenoceptor antagonist BMY 7378 is also an alpha (2C)-adrenoceptor antagonist". Autonomic and Autacoid Pharmacology. 25 (4): 135–41. doi:10.1111/j.1474-8673.2005.00342.x. PMID 16176444.
^Sallinen J, Höglund I, Engström M, Lehtimäki J, Virtanen R, Sirviö J, Wurster S, Savola JM, Haapalinna A (2007). "Pharmacological characterization and CNS effects of a novel highly selective alpha2C-adrenoceptor antagonist JP-1302". Br. J. Pharmacol. 150 (4): 391–402. doi:10.1038/sj.bjp.0707005. PMC2189732. PMID 17220913.
^Patel SD, Habeski WM, Min H, Zhang J, Roof R, Snyder B, Bora G, Campbell B, Li C, Hidayetoglu D, Johnson DS, Chaudhry A, Charlton ME, Kablaoui NM (2008). "Identification and SAR around N-{2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl}-2-phenoxy-nicotinamide, a selective alpha2C adrenergic receptor antagonist". Bioorg. Med. Chem. Lett. 18 (20): 5689–93. doi:10.1016/j.bmcl.2008.08.055. PMID 18799310.
^Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL (September 2008). "N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity". Neuropsychopharmacology. 33 (10): 2303–12. doi:10.1038/sj.npp.1301646. PMID 18059438.
^Bavadekar SA, Ma G, Mustafa SM, Moore BM, Miller DD, Feller DR (November 2006). "Tethered yohimbine analogs as selective human alpha2C-adrenergic receptor ligands". J. Pharmacol. Exp. Ther. 319 (2): 739–48. doi:10.1124/jpet.106.105981. PMID 16873606. S2CID 31412932.
External links
Human ADRA2C genome location and ADRA2C gene details page in the UCSC Genome Browser.
Further reading
Coupry I, Duzic E, Lanier SM (1992). "Factors determining the specificity of signal transduction by guanine nucleotide-binding protein-coupled receptors. II. Preferential coupling of the alpha 2C-adrenergic receptor to the guanine nucleotide-binding protein, Go". J. Biol. Chem. 267 (14): 9852–7. doi:10.1016/S0021-9258(19)50172-7. PMID 1349607.
Chhajlani V, Rangel N, Uhlén S, Wikberg JE (1991). "Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR". FEBS Lett. 280 (2): 241–4. doi:10.1016/0014-5793(91)80301-I. PMID 1849485. S2CID 26642747.
Regan JW, Kobilka TS, Yang-Feng TL, Caron MG, Lefkowitz RJ, Kobilka BK (1988). "Cloning and expression of a human kidney cDNA for an alpha 2-adrenergic receptor subtype". Proc. Natl. Acad. Sci. U.S.A. 85 (17): 6301–5. Bibcode:1988PNAS...85.6301R. doi:10.1073/pnas.85.17.6301. PMC281957. PMID 2842764.
Eason MG, Liggett SB (1993). "Human alpha 2-adrenergic receptor subtype distribution: widespread and subtype-selective expression of alpha 2C10, alpha 2C4, and alpha 2C2 mRNA in multiple tissues". Mol. Pharmacol. 44 (1): 70–5. PMID 7688069.
Riess O, Thies U, Siedlaczck I, Potisek S, Graham R, Theilmann J, Grimm T, Epplen JT, Hayden MR (1994). "Precise mapping of the brain alpha 2-adrenergic receptor gene within chromosome 4p16". Genomics. 19 (2): 298–302. doi:10.1006/geno.1994.1061. PMID 8188260.
Klein U, Ramirez MT, Kobilka BK, von Zastrow M (1997). "A novel interaction between adrenergic receptors and the alpha-subunit of eukaryotic initiation factor 2B". J. Biol. Chem. 272 (31): 19099–102. doi:10.1074/jbc.272.31.19099. PMID 9235896.
Schaak S, Devedjian JC, Cayla C, Sender Y, Paris H (1998). "Molecular cloning, sequencing and functional study of the promoter region of the human alpha2C4-adrenergic receptor gene". Biochem. J. 328 (2): 431–8. doi:10.1042/bj3280431. PMC1218938. PMID 9371698.
DeGraff JL, Gagnon AW, Benovic JL, Orsini MJ (1999). "Role of arrestins in endocytosis and signaling of alpha2-adrenergic receptor subtypes". J. Biol. Chem. 274 (16): 11253–9. doi:10.1074/jbc.274.16.11253. PMID 10196213.
Prezeau L, Richman JG, Edwards SW, Limbird LE (1999). "The zeta isoform of 14-3-3 proteins interacts with the third intracellular loop of different alpha2-adrenergic receptor subtypes". J. Biol. Chem. 274 (19): 13462–9. doi:10.1074/jbc.274.19.13462. PMID 10224112.
Small KM, Forbes SL, Rahman FF, Bridges KM, Liggett SB (2000). "A four amino acid deletion polymorphism in the third intracellular loop of the human alpha 2C-adrenergic receptor confers impaired coupling to multiple effectors". J. Biol. Chem. 275 (30): 23059–64. doi:10.1074/jbc.M000796200. PMID 10801795.
Comings DE, Gade-Andavolu R, Gonzalez N, Wu S, Muhleman D, Blake H, Chiu F, Wang E, Farwell K, Darakjy S, Baker R, Dietz G, Saucier G, MacMurray JP (2001). "Multivariate analysis of associations of 42 genes in ADHD, ODD and conduct disorder". Clin. Genet. 58 (1): 31–40. doi:10.1034/j.1399-0004.2000.580106.x. PMID 10945659. S2CID 43815350.
Small KM, Wagoner LE, Levin AM, Kardia SL, Liggett SB (2002). "Synergistic polymorphisms of beta1- and alpha2C-adrenergic receptors and the risk of congestive heart failure". N. Engl. J. Med. 347 (15): 1135–42. doi:10.1056/NEJMoa020803. PMID 12374873.
Chotani MA, Mitra S, Su BY, Flavahan S, Eid AH, Clark KR, Montague CR, Paris H, Handy DE, Flavahan NA (2004). "Regulation of alpha(2)-adrenoceptors in human vascular smooth muscle cells". Am. J. Physiol. Heart Circ. Physiol. 286 (1): H59–67. doi:10.1152/ajpheart.00268.2003. PMID 12946937.
Small KM, Mialet-Perez J, Seman CA, Theiss CT, Brown KM, Liggett SB (2004). "Polymorphisms of cardiac presynaptic alpha2C adrenergic receptors: Diverse intragenic variability with haplotype-specific functional effects". Proc. Natl. Acad. Sci. U.S.A. 101 (35): 13020–5. Bibcode:2004PNAS..10113020S. doi:10.1073/pnas.0405074101. PMC516511. PMID 15319474.
Chotani MA, Mitra S, Eid AH, Han SA, Flavahan NA (2005). "Distinct cAMP signaling pathways differentially regulate alpha2C-adrenoceptor expression: role in serum induction in human arteriolar smooth muscle cells". Am. J. Physiol. Heart Circ. Physiol. 288 (1): H69–76. doi:10.1152/ajpheart.01223.2003. PMID 15345481. S2CID 32149099.
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". J. Hum. Genet. 50 (1): 12–20. doi:10.1007/s10038-004-0211-y. PMID 15592690.
Neumeister A, Charney DS, Belfer I, Geraci M, Holmes C, Sharabi Y, Alim T, Bonne O, Luckenbaugh DA, Manji H, Goldman D, Goldstein DS (2005). "Sympathoneural and adrenomedullary functional effects of alpha2C-adrenoreceptor gene polymorphism in healthy humans". Pharmacogenet. Genomics. 15 (3): 143–9. doi:10.1097/01213011-200503000-00002. PMID 15861038. S2CID 479475.
Neumeister A, Drevets WC, Belfer I, Luckenbaugh DA, Henry S, Bonne O, Herscovitch P, Goldman D, Charney DS (2006). "Effects of an alpha 2C-adrenoreceptor gene polymorphism on neural responses to facial expressions in depression". Neuropsychopharmacology. 31 (8): 1750–6. doi:10.1038/sj.npp.1301010. PMID 16407897.
Park JS, Zhang SY, Jo SH, Seo JB, Li L, Park KW, Oh BH, Park YB, Kim HS (2006). "Common adrenergic receptor polymorphisms as novel risk factors for vasospastic angina". Am. Heart J. 151 (4): 864–9. doi:10.1016/j.ahj.2005.06.009. PMID 16569551.
March 04, 2023
alpha, adrenergic, receptor, alpha, adrenergic, receptor, α2c, adrenoceptor, also, known, adra2c, alpha, adrenergic, receptor, also, denotes, human, gene, encoding, adra2cidentifiersaliasesadra2c, adra2l2, adra2rl2, adrarl2, alpha2car, adrenoceptor, alpha, 2ce. The alpha 2C adrenergic receptor a2C adrenoceptor also known as ADRA2C is an alpha 2 adrenergic receptor and also denotes the human gene encoding it 5 ADRA2CIdentifiersAliasesADRA2C ADRA2L2 ADRA2RL2 ADRARL2 ALPHA2CAR adrenoceptor alpha 2CExternal IDsMGI 87936 HomoloGene 20170 GeneCards ADRA2CGene location Human Chr Chromosome 4 human 1 Band4p16 3Start3 766 348 bp 1 End3 768 526 bp 1 Gene location Mouse Chr Chromosome 5 mouse 2 Band5 B2 5 18 09 cMStart35 435 663 bp 2 End35 439 107 bp 2 RNA expression patternBgeeHumanMouse ortholog Top expressed incanal of the cervixascending aortapopliteal arterysaphenous veinvena cavaright coronary arterystromal cell of endometriumnippleputamenleft coronary arteryTop expressed innucleus accumbensentorhinal cortexsuperior frontal gyrusRegion I of hippocampus properretinal pigment epitheliumamygdalaolfactory tubercleinferior colliculushippocampus properprimary motor cortexMore reference expression dataBioGPSn aGene ontologyMolecular functionG protein coupled receptor activity epinephrine binding protein homodimerization activity signal transducer activity adrenergic receptor activity protein binding alpha 2A adrenergic receptor binding alpha2 adrenergic receptor activity protein heterodimerization activityCellular componentcytoplasm axon terminus integral component of membrane endosome membrane plasma membrane integral component of plasma membrane axon glutamatergic synapse integral component of postsynaptic membrane integral component of postsynaptic density membrane neuronal cell bodyBiological processG protein coupled receptor signaling pathway activation of protein kinase B activity negative regulation of epinephrine secretion regulation of sensory perception of pain regulation of smooth muscle contraction regulation of insulin secretion female pregnancy cell cell signaling negative regulation of norepinephrine secretion negative regulation of uterine smooth muscle contraction adenylate cyclase activating adrenergic receptor signaling pathway regulation of vasoconstriction positive regulation of neuron differentiation positive regulation of vasoconstriction signal transduction platelet activation positive regulation of MAPK cascade adrenergic receptor signaling pathway receptor transactivation adenylate cyclase modulating G protein coupled receptor signaling pathwaySources Amigo QuickGOOrthologsSpeciesHumanMouseEntrez15211553EnsemblENSG00000184160ENSMUSG00000045318UniProtP18825Q01337RefSeq mRNA NM 000683NM 007418RefSeq protein NP 000674NP 031444Location UCSC Chr 4 3 77 3 77 MbChr 5 35 44 35 44 MbPubMed search 3 4 WikidataView Edit HumanView Edit Mouse Contents 1 Receptor 2 Gene 3 Ligands 3 1 Agonists 3 2 Antagonists 4 See also 5 References 6 External links 7 Further readingReceptor EditAlpha 2 adrenergic receptors include 3 highly homologous subtypes alpha2A alpha2B and alpha2C These receptors have a critical role in regulating neurotransmitter release from sympathetic nerves and from adrenergic neurons in the central nervous system Studies in mice revealed that both the alpha2A and alpha2C subtypes were required for normal presynaptic control of transmitter release from sympathetic nerves in the heart and from central noradrenergic neurons the alpha2A subtype inhibited transmitter release at high stimulation frequencies whereas the alpha2C subtype modulated neurotransmission at lower levels of nerve activity 6 Gene EditThis gene encodes the alpha2C subtype which contains no introns in either its coding or untranslated sequences 5 Ligands EditAgonists Edit R 3 Nitrobiphenyline also weak antagonist at a2A and a2B 7 Antagonists Edit BMY 7378 also a1D antagonist 8 JP 1302 selective over a2A a2B a2C 9 N 2 4 2 3 dihydro benzo 1 4 dioxin 2 ylmethyl 1 4 diazepan 1 yl ethyl 2 phenoxy nicotinamide 10 Quetiapine 11 Risperidone Spiroxatrine Yohimbine derivatives 9 and 10 gt 43 fold selectivity over a2A a2B and a1 subtypes 12 BrexpiprazoleSee also EditAdrenergic receptorReferences Edit a b c GRCh38 Ensembl release 89 ENSG00000184160 Ensembl May 2017 a b c GRCm38 Ensembl release 89 ENSMUSG00000045318 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 ADRA2C adrenergic alpha 2C receptor ADRA2C adrenoceptor alpha 2C Homo sapiens human Gene NCBI www ncbi nlm nih gov Retrieved 2018 09 11 Crassous PA Cardinaletti C Carrieri A Bruni B Di Vaira M Gentili F Ghelfi F Giannella M Paris H Piergentili A Quaglia W Schaak S Vesprini C Pigini M August 2007 Alpha2 adrenoreceptors profile modulation 3 1 R m nitrobiphenyline a new efficient and alpha2C subtype selective agonist Journal of Medicinal Chemistry 50 16 3964 8 doi 10 1021 jm061487a PMID 17630725 Cleary L Murad K Bexis S Docherty JR 2005 The alpha 1D adrenoceptor antagonist BMY 7378 is also an alpha 2C adrenoceptor antagonist Autonomic and Autacoid Pharmacology 25 4 135 41 doi 10 1111 j 1474 8673 2005 00342 x PMID 16176444 Sallinen J Hoglund I Engstrom M Lehtimaki J Virtanen R Sirvio J Wurster S Savola JM Haapalinna A 2007 Pharmacological characterization and CNS effects of a novel highly selective alpha2C adrenoceptor antagonist JP 1302 Br J Pharmacol 150 4 391 402 doi 10 1038 sj bjp 0707005 PMC 2189732 PMID 17220913 Patel SD Habeski WM Min H Zhang J Roof R Snyder B Bora G Campbell B Li C Hidayetoglu D Johnson DS Chaudhry A Charlton ME Kablaoui NM 2008 Identification and SAR around N 2 4 2 3 dihydro benzo 1 4 dioxin 2 ylmethyl 1 4 diazepan 1 yl ethyl 2 phenoxy nicotinamide a selective alpha2C adrenergic receptor antagonist Bioorg Med Chem Lett 18 20 5689 93 doi 10 1016 j bmcl 2008 08 055 PMID 18799310 Jensen NH Rodriguiz RM Caron MG Wetsel WC Rothman RB Roth BL September 2008 N desalkylquetiapine a potent norepinephrine reuptake inhibitor and partial 5 HT1A agonist as a putative mediator of quetiapine s antidepressant activity Neuropsychopharmacology 33 10 2303 12 doi 10 1038 sj npp 1301646 PMID 18059438 Bavadekar SA Ma G Mustafa SM Moore BM Miller DD Feller DR November 2006 Tethered yohimbine analogs as selective human alpha2C adrenergic receptor ligands J Pharmacol Exp Ther 319 2 739 48 doi 10 1124 jpet 106 105981 PMID 16873606 S2CID 31412932 External links EditHuman ADRA2C genome location and ADRA2C gene details page in the UCSC Genome Browser Further reading EditCoupry I Duzic E Lanier SM 1992 Factors determining the specificity of signal transduction by guanine nucleotide binding protein coupled receptors II Preferential coupling of the alpha 2C adrenergic receptor to the guanine nucleotide binding protein Go J Biol Chem 267 14 9852 7 doi 10 1016 S0021 9258 19 50172 7 PMID 1349607 Chhajlani V Rangel N Uhlen S Wikberg JE 1991 Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR FEBS Lett 280 2 241 4 doi 10 1016 0014 5793 91 80301 I PMID 1849485 S2CID 26642747 Regan JW Kobilka TS Yang Feng TL Caron MG Lefkowitz RJ Kobilka BK 1988 Cloning and expression of a human kidney cDNA for an alpha 2 adrenergic receptor subtype Proc Natl Acad Sci U S A 85 17 6301 5 Bibcode 1988PNAS 85 6301R doi 10 1073 pnas 85 17 6301 PMC 281957 PMID 2842764 Eason MG Liggett SB 1993 Human alpha 2 adrenergic receptor subtype distribution widespread and subtype selective expression of alpha 2C10 alpha 2C4 and alpha 2C2 mRNA in multiple tissues Mol Pharmacol 44 1 70 5 PMID 7688069 Riess O Thies U Siedlaczck I Potisek S Graham R Theilmann J Grimm T Epplen JT Hayden MR 1994 Precise mapping of the brain alpha 2 adrenergic receptor gene within chromosome 4p16 Genomics 19 2 298 302 doi 10 1006 geno 1994 1061 PMID 8188260 Klein U Ramirez MT Kobilka BK von Zastrow M 1997 A novel interaction between adrenergic receptors and the alpha subunit of eukaryotic initiation factor 2B J Biol Chem 272 31 19099 102 doi 10 1074 jbc 272 31 19099 PMID 9235896 Schaak S Devedjian JC Cayla C Sender Y Paris H 1998 Molecular cloning sequencing and functional study of the promoter region of the human alpha2C4 adrenergic receptor gene Biochem J 328 2 431 8 doi 10 1042 bj3280431 PMC 1218938 PMID 9371698 DeGraff JL Gagnon AW Benovic JL Orsini MJ 1999 Role of arrestins in endocytosis and signaling of alpha2 adrenergic receptor subtypes J Biol Chem 274 16 11253 9 doi 10 1074 jbc 274 16 11253 PMID 10196213 Prezeau L Richman JG Edwards SW Limbird LE 1999 The zeta isoform of 14 3 3 proteins interacts with the third intracellular loop of different alpha2 adrenergic receptor subtypes J Biol Chem 274 19 13462 9 doi 10 1074 jbc 274 19 13462 PMID 10224112 Hein L Altman JD Kobilka BK 2000 Two functionally distinct alpha2 adrenergic receptors regulate sympathetic neurotransmission Nature 402 6758 181 4 doi 10 1038 46040 PMID 10647009 S2CID 205047992 Small KM Forbes SL Rahman FF Bridges KM Liggett SB 2000 A four amino acid deletion polymorphism in the third intracellular loop of the human alpha 2C adrenergic receptor confers impaired coupling to multiple effectors J Biol Chem 275 30 23059 64 doi 10 1074 jbc M000796200 PMID 10801795 Comings DE Gade Andavolu R Gonzalez N Wu S Muhleman D Blake H Chiu F Wang E Farwell K Darakjy S Baker R Dietz G Saucier G MacMurray JP 2001 Multivariate analysis of associations of 42 genes in ADHD ODD and conduct disorder Clin Genet 58 1 31 40 doi 10 1034 j 1399 0004 2000 580106 x PMID 10945659 S2CID 43815350 Small KM Wagoner LE Levin AM Kardia SL Liggett SB 2002 Synergistic polymorphisms of beta1 and alpha2C adrenergic receptors and the risk of congestive heart failure N Engl J Med 347 15 1135 42 doi 10 1056 NEJMoa020803 PMID 12374873 Chotani MA Mitra S Su BY Flavahan S Eid AH Clark KR Montague CR Paris H Handy DE Flavahan NA 2004 Regulation of alpha 2 adrenoceptors in human vascular smooth muscle cells Am J Physiol Heart Circ Physiol 286 1 H59 67 doi 10 1152 ajpheart 00268 2003 PMID 12946937 Small KM Mialet Perez J Seman CA Theiss CT Brown KM Liggett SB 2004 Polymorphisms of cardiac presynaptic alpha2C adrenergic receptors Diverse intragenic variability with haplotype specific functional effects Proc Natl Acad Sci U S A 101 35 13020 5 Bibcode 2004PNAS 10113020S doi 10 1073 pnas 0405074101 PMC 516511 PMID 15319474 Chotani MA Mitra S Eid AH Han SA Flavahan NA 2005 Distinct cAMP signaling pathways differentially regulate alpha2C adrenoceptor expression role in serum induction in human arteriolar smooth muscle cells Am J Physiol Heart Circ Physiol 288 1 H69 76 doi 10 1152 ajpheart 01223 2003 PMID 15345481 S2CID 32149099 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 J Hum Genet 50 1 12 20 doi 10 1007 s10038 004 0211 y PMID 15592690 Neumeister A Charney DS Belfer I Geraci M Holmes C Sharabi Y Alim T Bonne O Luckenbaugh DA Manji H Goldman D Goldstein DS 2005 Sympathoneural and adrenomedullary functional effects of alpha2C adrenoreceptor gene polymorphism in healthy humans Pharmacogenet Genomics 15 3 143 9 doi 10 1097 01213011 200503000 00002 PMID 15861038 S2CID 479475 Neumeister A Drevets WC Belfer I Luckenbaugh DA Henry S Bonne O Herscovitch P Goldman D Charney DS 2006 Effects of an alpha 2C adrenoreceptor gene polymorphism on neural responses to facial expressions in depression Neuropsychopharmacology 31 8 1750 6 doi 10 1038 sj npp 1301010 PMID 16407897 Park JS Zhang SY Jo SH Seo JB Li L Park KW Oh BH Park YB Kim HS 2006 Common adrenergic receptor polymorphisms as novel risk factors for vasospastic angina Am Heart J 151 4 864 9 doi 10 1016 j ahj 2005 06 009 PMID 16569551 Retrieved from https en wikipedia org w index php title Alpha 2C adrenergic receptor amp oldid 1136292661, wikipedia, wiki, book, books, library,
