Alfa-2C adrenergički 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

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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]

Povezano

Adrenergički receptor

Reference

↑ ^1,0 ^1,1 „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 (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.
↑ Sallinen J, Höglund I, Engström M, et al (February 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.
↑ 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.
↑ Patel SD, Habeski WM, Min H, et al (October 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. DOI:10.1016/j.bmcl.2008.08.055. PMID 18799310.

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. DOI:10.1016/0014-5793(91)80301-I. PMID 1849485.
Regan JW, Kobilka TS, Yang-Feng TL, et al. (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. 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, et al. (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, et al. (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. 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.
Small KM, Forbes SL, Rahman FF, et al. (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, et al. (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.
Small KM, Wagoner LE, Levin AM, et al. (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, et al. (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, et al. (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. DOI:10.1073/pnas.0405074101. PMC 516511. PMID 15319474.
Chotani MA, Mitra S, Eid AH, et al. (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.
Belfer I, Buzas B, Hipp H, et al. (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, et al. (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.
Neumeister A, Drevets WC, Belfer I, et al. (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, et al. (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.

Spoljašnje veze

„α_2C-adrenoceptor”. IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Arhivirano iz originala na datum 2016-03-04.

[entrez-1] 1,0 ^1,1 „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 (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.

[pmid17220913-3] Sallinen J, Höglund I, Engström M, et al (February 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.

[pmid16873606-4] 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.

[pmid18799310-5] Patel SD, Habeski WM, Min H, et al (October 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. DOI:10.1016/j.bmcl.2008.08.055. PMID 18799310.

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