Biology:Alpha-2C adrenergic receptor

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

The alpha-2C adrenergic receptor (α_2C adrenoceptor), also known as ADRA2C, is an alpha-2 adrenergic receptor, and also denotes the human gene encoding it.

Receptor

Alpha-2-adrenergic receptors include 3 highly homologous subtypes: alpha_2A, alpha_2B, and alpha_2C. 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 alpha_2A and alpha_2C subtypes were required for normal presynaptic control of transmitter release from sympathetic nerves in the heart and from central noradrenergic neurons; the alpha_2A subtype inhibited transmitter release at high stimulation frequencies, whereas the alpha_2C subtype modulated neurotransmission at lower levels of nerve activity.

Gene

This gene encodes the alpha2C subtype, which contains no introns in either its coding or untranslated sequences.

Ligands

Agonists

• (R)-3-Nitrobiphenyline (also weak antagonist at α_2A and α_2B)

Antagonists

• BMY 7378 (also α_1D antagonist)
• JP-1302: selective over α2A, α2B, α2C
• N-{2-[4-(2,3-dihydro-benzo[1,4]dioxin-2-ylmethyl)-[1,4]diazepan-1-yl]-ethyl}-2-phenoxy-nicotinamide
• Quetiapine
• Risperidone
• Mirtazapine
• Spiroxatrine
• Yohimbine derivatives 9 and 10: >43 fold selectivity over α2A, α2B and α1 subtypes
• Brexpiprazole

See also

• Adrenergic receptor

External links

• Human ADRA2C genome location and ADRA2C gene details page in the UCSC Genome Browser.

Further reading

• "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. 1992. doi:10.1016/S0021-9258(19)50172-7. PMID 1349607. 
• "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. 1991. doi:10.1016/0014-5793(91)80301-I. PMID 1849485. 
• "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. 1988. doi:10.1073/pnas.85.17.6301. PMID 2842764. Bibcode: 1988PNAS...85.6301R. 
• "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. 1993. PMID 7688069. 
• "Precise mapping of the brain alpha 2-adrenergic receptor gene within chromosome 4p16". Genomics 19 (2): 298–302. 1994. doi:10.1006/geno.1994.1061. PMID 8188260. 
• "A novel interaction between adrenergic receptors and the alpha-subunit of eukaryotic initiation factor 2B". J. Biol. Chem. 272 (31): 19099–102. 1997. doi:10.1074/jbc.272.31.19099. PMID 9235896. 
• "Molecular cloning, sequencing and functional study of the promoter region of the human alpha2C4-adrenergic receptor gene". Biochem. J. 328 (2): 431–8. 1998. doi:10.1042/bj3280431. PMID 9371698. 
• "Role of arrestins in endocytosis and signaling of alpha2-adrenergic receptor subtypes". J. Biol. Chem. 274 (16): 11253–9. 1999. doi:10.1074/jbc.274.16.11253. PMID 10196213. 
• "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. 1999. doi:10.1074/jbc.274.19.13462. PMID 10224112. 
• "Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission". Nature 402 (6758): 181–4. 2000. doi:10.1038/46040. PMID 10647009. 
• "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. 2000. doi:10.1074/jbc.M000796200. PMID 10801795. 
• "Multivariate analysis of associations of 42 genes in ADHD, ODD and conduct disorder". Clin. Genet. 58 (1): 31–40. 2001. doi:10.1034/j.1399-0004.2000.580106.x. PMID 10945659. 
• "Synergistic polymorphisms of beta1- and alpha2C-adrenergic receptors and the risk of congestive heart failure". N. Engl. J. Med. 347 (15): 1135–42. 2002. doi:10.1056/NEJMoa020803. PMID 12374873. 
• "Regulation of alpha(2)-adrenoceptors in human vascular smooth muscle cells". Am. J. Physiol. Heart Circ. Physiol. 286 (1): H59–67. 2004. doi:10.1152/ajpheart.00268.2003. PMID 12946937. 
• "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. 2004. doi:10.1073/pnas.0405074101. PMID 15319474. Bibcode: 2004PNAS..10113020S. 
• "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. 2005. doi:10.1152/ajpheart.01223.2003. PMID 15345481. 
• "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. 2005. doi:10.1007/s10038-004-0211-y. PMID 15592690. 
• "Sympathoneural and adrenomedullary functional effects of alpha2C-adrenoreceptor gene polymorphism in healthy humans". Pharmacogenet. Genomics 15 (3): 143–9. 2005. doi:10.1097/01213011-200503000-00002. PMID 15861038. 
• "Effects of an alpha 2C-adrenoreceptor gene polymorphism on neural responses to facial expressions in depression". Neuropsychopharmacology 31 (8): 1750–6. 2006. doi:10.1038/sj.npp.1301010. PMID 16407897. 
• "Common adrenergic receptor polymorphisms as novel risk factors for vasospastic angina". Am. Heart J. 151 (4): 864–9. 2006. doi:10.1016/j.ahj.2005.06.009. PMID 16569551.