Alpha-2C adrenergic receptor

{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc}} {{Infobox_gene}} 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.<ref name="entrez" />

== Receptor ==

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.<ref>{{Cite web|url=https://www.ncbi.nlm.nih.gov/gene/152|title=ADRA2C adrenoceptor alpha 2C [Homo sapiens (human)] - Gene - NCBI|website=www.ncbi.nlm.nih.gov|language=en|access-date=2018-09-11}}</ref>

== Gene ==

This gene encodes the alpha2C subtype, which contains no introns in either its coding or untranslated sequences.<ref name="entrez">{{cite web | title = Entrez Gene: ADRA2C adrenergic, alpha-2C-, receptor| url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=152}}</ref>

== Ligands ==

=== Agonists ===

* (R)-3-Nitrobiphenyline (also weak antagonist at α2A and α2B)<ref name="pmid17630725">{{cite journal | vauthors = 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 | title = Alpha2-adrenoreceptors profile modulation. 3.1 (R)-(+)-m-nitrobiphenyline, a new efficient and alpha2C-subtype selective agonist | journal = Journal of Medicinal Chemistry | volume = 50 | issue = 16 | pages = 3964–8 | date = August 2007 | pmid = 17630725 | doi = 10.1021/jm061487a }}</ref>

=== Antagonists === * BMY 7378 (also α1D antagonist)<ref name="pmid16176444">{{cite journal | vauthors = Cleary L, Murad K, Bexis S, Docherty JR | title = The alpha (1D)-adrenoceptor antagonist BMY 7378 is also an alpha (2C)-adrenoceptor antagonist | journal = Autonomic and Autacoid Pharmacology | volume = 25 | issue = 4 | pages = 135–41 | year = 2005 | pmid = 16176444 | doi = 10.1111/j.1474-8673.2005.00342.x }}</ref> * Brexpiprazole * JP-1302: selective over α2A, α2B, α2C<ref name="pmid17220913">{{cite journal | vauthors = Sallinen J, Höglund I, Engström M, Lehtimäki J, Virtanen R, Sirviö J, Wurster S, Savola JM, Haapalinna A | title = Pharmacological characterization and CNS effects of a novel highly selective alpha2C-adrenoceptor antagonist JP-1302 | journal = Br. J. Pharmacol. | volume = 150 | issue = 4 | pages = 391–402 | year = 2007 | pmid = 17220913 | pmc = 2189732 | doi = 10.1038/sj.bjp.0707005 }}</ref> * ''N''-{2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl}-2-phenoxy-nicotinamide<ref name="pmid18799310">{{cite journal | vauthors = 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 | title = 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 | journal = Bioorg. Med. Chem. Lett. | volume = 18 | issue = 20 | pages = 5689–93 | year = 2008 | pmid = 18799310 | doi = 10.1016/j.bmcl.2008.08.055 }}</ref> * Pirepemat * Quetiapine<ref name="pmid18059438">{{cite journal|author6-link=Bryan Roth | vauthors = Jensen NH, Rodriguiz RM, Caron MG, Wetsel WC, Rothman RB, Roth BL | title = N-desalkylquetiapine, a potent norepinephrine reuptake inhibitor and partial 5-HT1A agonist, as a putative mediator of quetiapine's antidepressant activity | journal = Neuropsychopharmacology | volume = 33 | issue = 10 | pages = 2303–12 | date = September 2008 | pmid = 18059438 | doi = 10.1038/sj.npp.1301646 | doi-access = free }}</ref> * Risperidone * Mirtazapine * Spiroxatrine * Yohimbine derivatives 9 and 10: >43 fold selectivity over α2A, α2B and α1 subtypes<ref name="pmid16873606">{{cite journal | vauthors = Bavadekar SA, Ma G, Mustafa SM, Moore BM, Miller DD, Feller DR | title = Tethered yohimbine analogs as selective human alpha2C-adrenergic receptor ligands | journal = J. Pharmacol. Exp. Ther. | volume = 319 | issue = 2 | pages = 739–48 | date = November 2006 | pmid = 16873606 | doi = 10.1124/jpet.106.105981 | s2cid = 31412932 }}</ref>

== See also == *Adrenergic receptor

== References == {{reflist|35em}}

==External links== * {{UCSC gene info|ADRA2C}}

== Further reading == {{refbegin|35em}} *{{cite journal | vauthors = Coupry I, Duzic E, Lanier SM | title = 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 | journal = J. Biol. Chem. | volume = 267 | issue = 14 | pages = 9852–7 | year = 1992 | doi = 10.1016/S0021-9258(19)50172-7 | pmid = 1349607 | doi-access = free }} *{{cite journal | vauthors = Chhajlani V, Rangel N, Uhlén S, Wikberg JE | title = Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR | journal = FEBS Lett. | volume = 280 | issue = 2 | pages = 241–4 | year = 1991 | pmid = 1849485 | doi = 10.1016/0014-5793(91)80301-I | s2cid = 26642747 | doi-access = free }} *{{cite journal | vauthors = Regan JW, Kobilka TS, Yang-Feng TL, Caron MG, Lefkowitz RJ, Kobilka BK | title = Cloning and expression of a human kidney cDNA for an alpha 2-adrenergic receptor subtype | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 85 | issue = 17 | pages = 6301–5 | year = 1988 | pmid = 2842764 | pmc = 281957 | doi = 10.1073/pnas.85.17.6301 | bibcode = 1988PNAS...85.6301R | doi-access = free }} *{{cite journal | vauthors = Eason MG, Liggett SB | title = Human alpha 2-adrenergic receptor subtype distribution: widespread and subtype-selective expression of alpha 2C10, alpha 2C4, and alpha 2C2 mRNA in multiple tissues | journal = Mol. Pharmacol. | volume = 44 | issue = 1 | pages = 70–5 | year = 1993 | pmid = 7688069 }} *{{cite journal | vauthors = Riess O, Thies U, Siedlaczck I, Potisek S, Graham R, Theilmann J, Grimm T, Epplen JT, Hayden MR | title = Precise mapping of the brain alpha 2-adrenergic receptor gene within chromosome 4p16 | journal = Genomics | volume = 19 | issue = 2 | pages = 298–302 | year = 1994 | pmid = 8188260 | doi = 10.1006/geno.1994.1061 }} *{{cite journal | vauthors = Klein U, Ramirez MT, Kobilka BK, von Zastrow M | title = A novel interaction between adrenergic receptors and the alpha-subunit of eukaryotic initiation factor 2B | journal = J. Biol. Chem. | volume = 272 | issue = 31 | pages = 19099–102 | year = 1997 | pmid = 9235896 | doi = 10.1074/jbc.272.31.19099 | doi-access = free }} *{{cite journal | vauthors = Schaak S, Devedjian JC, Cayla C, Sender Y, Paris H | title = Molecular cloning, sequencing and functional study of the promoter region of the human alpha2C4-adrenergic receptor gene | journal = Biochem. J. | volume = 328 | issue = 2 | pages = 431–8 | year = 1998 | pmid = 9371698 | pmc = 1218938 | doi = 10.1042/bj3280431}} *{{cite journal | vauthors = DeGraff JL, Gagnon AW, Benovic JL, Orsini MJ | title = Role of arrestins in endocytosis and signaling of alpha2-adrenergic receptor subtypes | journal = J. Biol. Chem. | volume = 274 | issue = 16 | pages = 11253–9 | year = 1999 | pmid = 10196213 | doi = 10.1074/jbc.274.16.11253 | doi-access = free }} *{{cite journal | vauthors = Prezeau L, Richman JG, Edwards SW, Limbird LE | title = The zeta isoform of 14-3-3 proteins interacts with the third intracellular loop of different alpha2-adrenergic receptor subtypes | journal = J. Biol. Chem. | volume = 274 | issue = 19 | pages = 13462–9 | year = 1999 | pmid = 10224112 | doi = 10.1074/jbc.274.19.13462 | doi-access = free }} *{{cite journal | vauthors = Hein L, Altman JD, Kobilka BK | title = Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission | journal = Nature | volume = 402 | issue = 6758 | pages = 181–4 | year = 2000 | pmid = 10647009 | doi = 10.1038/46040 | bibcode = 1999Natur.402..181H | s2cid = 205047992 }} *{{cite journal | vauthors = Small KM, Forbes SL, Rahman FF, Bridges KM, Liggett SB | title = A four amino acid deletion polymorphism in the third intracellular loop of the human alpha 2C-adrenergic receptor confers impaired coupling to multiple effectors | journal = J. Biol. Chem. | volume = 275 | issue = 30 | pages = 23059–64 | year = 2000 | pmid = 10801795 | doi = 10.1074/jbc.M000796200 |doi-access=free }} *{{cite journal | vauthors = 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 | title = Multivariate analysis of associations of 42 genes in ADHD, ODD and conduct disorder | journal = Clin. Genet. | volume = 58 | issue = 1 | pages = 31–40 | year = 2001 | pmid = 10945659 | doi = 10.1034/j.1399-0004.2000.580106.x | s2cid = 43815350 }} *{{cite journal | vauthors = Small KM, Wagoner LE, Levin AM, Kardia SL, Liggett SB | title = Synergistic polymorphisms of beta1- and alpha2C-adrenergic receptors and the risk of congestive heart failure | journal = N. Engl. J. Med. | volume = 347 | issue = 15 | pages = 1135–42 | year = 2002 | pmid = 12374873 | doi = 10.1056/NEJMoa020803 | doi-access = free }} *{{cite journal | vauthors = Chotani MA, Mitra S, Su BY, Flavahan S, Eid AH, Clark KR, Montague CR, Paris H, Handy DE, Flavahan NA | title = Regulation of alpha(2)-adrenoceptors in human vascular smooth muscle cells | journal = Am. J. Physiol. Heart Circ. Physiol. | volume = 286 | issue = 1 | pages = H59–67 | year = 2004 | pmid = 12946937 | doi = 10.1152/ajpheart.00268.2003 }} *{{cite journal | vauthors = Small KM, Mialet-Perez J, Seman CA, Theiss CT, Brown KM, Liggett SB | title = Polymorphisms of cardiac presynaptic alpha2C adrenergic receptors: Diverse intragenic variability with haplotype-specific functional effects | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 101 | issue = 35 | pages = 13020–5 | year = 2004 | pmid = 15319474 | pmc = 516511 | doi = 10.1073/pnas.0405074101 | bibcode = 2004PNAS..10113020S | doi-access = free }} *{{cite journal | vauthors = Chotani MA, Mitra S, Eid AH, Han SA, Flavahan NA | title = Distinct cAMP signaling pathways differentially regulate alpha2C-adrenoceptor expression: role in serum induction in human arteriolar smooth muscle cells | journal = Am. J. Physiol. Heart Circ. Physiol. | volume = 288 | issue = 1 | pages = H69–76 | year = 2005 | pmid = 15345481 | doi = 10.1152/ajpheart.01223.2003 | s2cid = 32149099 }} *{{cite journal | vauthors = Belfer I, Buzas B, Hipp H, Phillips G, Taubman J, Lorincz I, Evans C, Lipsky RH, Enoch MA, Max MB, Goldman D | title = Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene | journal = J. Hum. Genet. | volume = 50 | issue = 1 | pages = 12–20 | year = 2005 | pmid = 15592690 | doi = 10.1007/s10038-004-0211-y | doi-access = free }} *{{cite journal | vauthors = Neumeister A, Charney DS, Belfer I, Geraci M, Holmes C, Sharabi Y, Alim T, Bonne O, Luckenbaugh DA, Manji H, Goldman D, Goldstein DS | title = Sympathoneural and adrenomedullary functional effects of alpha2C-adrenoreceptor gene polymorphism in healthy humans | journal = Pharmacogenet. Genomics | volume = 15 | issue = 3 | pages = 143–9 | year = 2005 | pmid = 15861038 | doi = 10.1097/01213011-200503000-00002 | s2cid = 479475 }} *{{cite journal | vauthors = Neumeister A, Drevets WC, Belfer I, Luckenbaugh DA, Henry S, Bonne O, Herscovitch P, Goldman D, Charney DS | title = Effects of an alpha 2C-adrenoreceptor gene polymorphism on neural responses to facial expressions in depression | journal = Neuropsychopharmacology | volume = 31 | issue = 8 | pages = 1750–6 | year = 2006 | pmid = 16407897 | doi = 10.1038/sj.npp.1301010 | doi-access = free }} *{{cite journal | vauthors = Park JS, Zhang SY, Jo SH, Seo JB, Li L, Park KW, Oh BH, Park YB, Kim HS | title = Common adrenergic receptor polymorphisms as novel risk factors for vasospastic angina | journal = Am. Heart J. | volume = 151 | issue = 4 | pages = 864–9 | year = 2006 | pmid = 16569551 | doi = 10.1016/j.ahj.2005.06.009 }} {{refend}}

Category:Adrenergic receptors