Alfa-2C adrenergički receptor

Adrenergički alfa-2C receptor
Adrenergički alfa-2C receptor
	PDB prikaz baziran na 1hll.
Dostupne strukture
	1hll, 1ho9, 1hod, 1hof
Identifikatori
Simboli	ADRA2C; ADRA2L2; ADRA2RL2; ADRARL2; ALPHA2CAR
Vanjski ID	OMIM: 104250 MGI: 87936 HomoloGene: 20170 IUPHAR: α2C-adrenoceptor GeneCards: ADRA2C Gene
Ontologija gena
Molekularna funkcija	• aktivnost rodopsinu-sličnog receptora; • receptorska aktivnost; • adrenoceptorska aktivnost; • aktivnost alfa2-adrenergičkog receptora;
Celularna komponenta	• endosome; • integralno sa ćelijskom membranom; • membrana; • integralno sa membranom;
Biološki proces	• aktivacija MAPK aktivnosti; • prenos signala; • signalni put G-protein spregnutog receptora; • interćelijska signalizacija; • ponašanje;
Ortolozi
Vrsta	Čovek
Entrez	152
Ensembl	ENSG00000184160
UniProt	P18825
RefSeq (mRNA)	XM_001128592
RefSeq (protein)	XP_001128592
Lokacija (UCSC)	n/a
PubMed pretraga	[1]

Alfa-2C adrenergički receptor (α_2C adrenoceptor, ADRA2C) je alfa-2 adrenergički receptor. On je kodiran humanim ADRA2C genom.^[1]

Receptor

Alfa-2-adrenergički receptori su 3 visoko homologna podtipa: alfa_2A, alfa_2B, i alfa_2C. Ti receptori imaju kritičnu ulogu u regulaciji otpuštanja neurotransmitera iz simpatičkih nerva i iz adrenergičkih neurona centralnog nervnog sistema. Ispitivanja na miševima su pokazala da su oba, alfa_2A i alfa_2C, podtipa neophodna za normalnu presinaptičku kontrolu otpuštanja transmitera iz simpatičkih nerva u srcu i iz centralnih noradrenergičkih neurona. Alfa_2A podtip inhibira otpuštanje transmitera na visokim stimulacionim frekvencijama, dok alfa_2C podtip modulira neurotransmisiju na niskim nivoima nervne aktivnosti.

Gen

Ovaj gen kodira alfa2C tip receptora. On ne sadrži introne.^[1]

Ligandi

Agonisti

(R)-3-Nitrobifenilin (takođe slab antagonist α_2A i α_2B)^[2]

Antagonisti

JP-1302: selektivan u odnosu na α2A, α2B, α2D^[3]
spiroksatrin
johimbin derivati 9 i 10: >43 puta selektivniji nego za α2A, α2B i α1 tipove^[4]
N2-[4-(2,3-dihidro-benzo[1,4]dioksin-2-ilmetil)-[1,4]diazepan-1-il]-etil2-fenoksi-nikotinamid^[5]

Vidi još

Adrenergički receptor

Reference

^ ^а ^б „Entrez Gene: ADRA2C adrenergic, alpha-2C-, receptor”.
^ 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 (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. PMID 17630725. doi:10.1021/jm061487a.
^ J, Sallinen; Höglund I; Engström M (2007). „Pharmacological characterization and CNS effects of a novel highly selective alpha2C-adrenoceptor antagonist JP-1302”. Br. J. Pharmacol. 150 (4): 391—402. PMC 2189732 . PMID 17220913. doi:10.1038/sj.bjp.0707005.
^ Bavadekar SA, Ma G, Mustafa SM, Moore BM, Miller DD, Feller DR (2006). „Tethered yohimbine analogs as selective human alpha2C-adrenergic receptor ligands”. J. Pharmacol. Exp. Ther. 319 (2): 739—48. PMID 16873606. doi:10.1124/jpet.106.105981.
^ SD, Patel; Habeski WM; Min H (2008). „Identification and SAR around N2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl2-phenoxy-nicotinamide, a selective alpha2C adrenergic receptor antagonist”. Bioorg. Med. Chem. Lett. 18 (20): 5689—93. PMID 18799310. doi:10.1016/j.bmcl.2008.08.055.

Literatura

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. 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. PMID 1849485. doi:10.1016/0014-5793(91)80301-I.
JW, Regan; Kobilka TS; Yang-Feng TL (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. PMC 281957 . PMID 2842764. doi:10.1073/pnas.85.17.6301.
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.
O, Riess; Thies U; Siedlaczck I (1994). „Precise mapping of the brain alpha 2-adrenergic receptor gene within chromosome 4p16.”. Genomics. 19 (2): 298—302. PMID 8188260. doi:10.1006/geno.1994.1061.
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. PMID 9235896. doi:10.1074/jbc.272.31.19099.
S, Schaak; Devedjian JC; Cayla C (1998). „Molecular cloning, sequencing and functional study of the promoter region of the human alpha2C4-adrenergic receptor gene.”. Biochem. J. 328 ( Pt 2): 431—8. 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. PMID 10196213. doi:10.1074/jbc.274.16.11253.
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. PMID 10224112. doi:10.1074/jbc.274.19.13462.
Hein L, Altman JD, Kobilka BK (2000). „Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission.”. Nature. 402 (6758): 181—4. PMID 10647009. doi:10.1038/46040.
KM, Small; Forbes SL; Rahman FF (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. PMID 10801795. doi:10.1074/jbc.M000796200.
DE, Comings; Gade-Andavolu R; Gonzalez N (2001). „Multivariate analysis of associations of 42 genes in ADHD, ODD and conduct disorder.”. Clin. Genet. 58 (1): 31—40. PMID 10945659. doi:10.1034/j.1399-0004.2000.580106.x.
KM, Small; Wagoner LE; Levin AM (2002). „Synergistic polymorphisms of beta1- and alpha2C-adrenergic receptors and the risk of congestive heart failure.”. N. Engl. J. Med. 347 (15): 1135—42. PMID 12374873. doi:10.1056/NEJMoa020803.
MA, Chotani; Mitra S; Su BY (2004). „Regulation of alpha(2)-adrenoceptors in human vascular smooth muscle cells.”. Am. J. Physiol. Heart Circ. Physiol. 286 (1): H59—67. PMID 12946937. doi:10.1152/ajpheart.00268.2003.
KM, Small; Mialet-Perez J; Seman CA (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. PMC 516511 . PMID 15319474. doi:10.1073/pnas.0405074101.
MA, Chotani; Mitra S; Eid AH (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. PMID 15345481. doi:10.1152/ajpheart.01223.2003.
I, Belfer; Buzas B; Hipp H (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. PMID 15592690. doi:10.1007/s10038-004-0211-y.
A, Neumeister; Charney DS; Belfer I (2005). „Sympathoneural and adrenomedullary functional effects of alpha2C-adrenoreceptor gene polymorphism in healthy humans.”. Pharmacogenet. Genomics. 15 (3): 143—9. PMID 15861038. doi:10.1097/01213011-200503000-00002.
A, Neumeister; Drevets WC; Belfer I (2006). „Effects of an alpha 2C-adrenoreceptor gene polymorphism on neural responses to facial expressions in depression.”. Neuropsychopharmacology. 31 (8): 1750—6. PMID 16407897. doi:10.1038/sj.npp.1301010.
JS, Park; Zhang SY; Jo SH (2006). „Common adrenergic receptor polymorphisms as novel risk factors for vasospastic angina.”. Am. Heart J. 151 (4): 864—9. PMID 16569551. doi:10.1016/j.ahj.2005.06.009.

Spoljašnje veze

„α_2C-adrenoceptor”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.

[entrez-1] а ^б „Entrez Gene: ADRA2C adrenergic, alpha-2C-, receptor”.

[pmid17630725-2] 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 (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. PMID 17630725. doi:10.1021/jm061487a.

[pmid17220913-3] J, Sallinen; Höglund I; Engström M (2007). „Pharmacological characterization and CNS effects of a novel highly selective alpha2C-adrenoceptor antagonist JP-1302”. Br. J. Pharmacol. 150 (4): 391—402. PMC 2189732 . PMID 17220913. doi:10.1038/sj.bjp.0707005.

[pmid16873606-4] Bavadekar SA, Ma G, Mustafa SM, Moore BM, Miller DD, Feller DR (2006). „Tethered yohimbine analogs as selective human alpha2C-adrenergic receptor ligands”. J. Pharmacol. Exp. Ther. 319 (2): 739—48. PMID 16873606. doi:10.1124/jpet.106.105981.

[pmid18799310-5] SD, Patel; Habeski WM; Min H (2008). „Identification and SAR around N2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl2-phenoxy-nicotinamide, a selective alpha2C adrenergic receptor antagonist”. Bioorg. Med. Chem. Lett. 18 (20): 5689—93. PMID 18799310. doi:10.1016/j.bmcl.2008.08.055.

[1]

[2]

[3]

[4]

[5]