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ADRA2A  -  adrenoceptor alpha 2A

Homo sapiens

Synonyms: ADRA2, ADRA2R, ADRAR, ALPHA2AAR, Alpha-2 adrenergic receptor subtype C10, ...
 
 
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Disease relevance of ADRA2A

  • Sequence variations in the human alpha2 adrenergic receptor genes (ADRA2A and ADRA2C) have been implicated as a cause of hypertension in blacks [1].
  • The alpha 2A-adrenergic receptor (adrenoceptor) was stably expressed in AtT20 mouse pituitary tumor cells; adrenoceptor agonists inhibited adenylyl cyclase, inhibited voltage-dependent calcium currents, and increased inwardly rectifying potassium currents [2].
  • Pertussis toxin treatment markedly reduced this to approximately 19% with S1,2,3, while having no effect on beta 2AR and completely eliminating high affinity agonist binding to alpha 2AAR [3].
  • The density of the alpha 2A-adrenergic receptor in the HT29 cell line, a human colonic adenocarcinoma, increases when the cells are placed in fetal calf serum (FCS)-free culture medium and decreases again, in a concentration-dependent manner, when they are re-exposed to FCS [4].
 

Psychiatry related information on ADRA2A

 

High impact information on ADRA2A

 

Chemical compound and disease context of ADRA2A

 

Biological context of ADRA2A

  • CONCLUSION: We describe novel variants and the haplotype structure of the ADRA2A gene [13].
  • BACKGROUND AND OBJECTIVES: The alpha2A-adrenergic receptor (ADRA2A) plays a central role in the regulation of systemic sympathetic activity and hence cardiovascular responses such as heart rate and blood pressure [13].
  • METHODS: We examined 5957 base pairs of contiguous sequence of ADRA2A (promoter, exonic, and 3'-flanking region) using polymerase chain reaction to amplify the genomic target, followed by bidirectional sequencing, in 135 healthy subjects (85 white and 50 black subjects) [13].
  • RESULTS: The allele frequencies of the ADRA2A C-1291G polymorphism differed between races [14].
  • RESULTS: For the Dra I ADRA2A RFLP, we observed a significant difference in genotype distributions between the two groups (P = 0.037) [15].
 

Anatomical context of ADRA2A

 

Associations of ADRA2A with chemical compounds

  • Common genetic ADRA2A variants are not important determinants of baseline cardiovascular measures (plasma norepinephrine, heart rate, and blood pressure) in healthy volunteers [13].
  • Recent findings suggesting an association between response to MPH and an MspI polymorphism in the promoter region of the alpha2A-adrenoceptor gene (ADRA2A) are discussed [20].
  • Naphazoline was the most selective compound for the high affinity state of the alpha-2A adrenoceptor, displaying 7-, 23- and 9-fold higher affinity than alpha-2B, alpha-2C and platelet I1-midazoline binding sites, respectively [21].
  • alpha2A adrenergic receptor (ADRA2A) on platelets interacts with epinephrine, which has a key role in regulating platelet functions [22].
  • Other measurements such as BMI, WHR, abdominal sagittal diameter, total testosterone, insulin-like growth factor I, serum leptin, fasting insulin and serum lipids were not different across the ADRA2A genotype groups [23].
 

Physical interactions of ADRA2A

  • 6. Since octopamine and synephrine occur naturally in, and are co-released with catecholamines from, mammalian tissues, the results of the present study suggest that the human cloned alpha 2A-adrenoceptor can be coupled selectively by different endogenous agonists to G-protein pathways mediating the regulation of adenylyl cyclase activity [24].
 

Enzymatic interactions of ADRA2A

 

Regulatory relationships of ADRA2A

 

Other interactions of ADRA2A

  • This study supports the hypothesis that an allele of the ADRA2A gene is associated and linked with the ADHD combined subtype and suggests that the DraI polymorphism of ADRA2A is linked to a causative polymorphism [27].
  • Detailed physical analysis of a 1.5-megabase YAC contig containing the MXI1 and ADRA2A genes [28].
  • ADRA2A and ADRA2B each had a single haplotype block at least 11 and 16 kb in size, respectively, in both populations [29].
  • Three genes encode alpha2-AR subtypes carrying common functional polymorphisms (ADRA2A Asn251Lys, ADRA2B Ins/Del301-303 and ADRA2C Ins/Del322-325) [29].
  • Two candidate genes stand out in these regions: the adrenergic receptor alpha 1C(1A) (ADRA1C) located on chromosome 8p and the adrenergic receptor alpha 2A (ADRA2A) located on chromosome 10q [30].
 

Analytical, diagnostic and therapeutic context of ADRA2A

References

  1. Do allelic variants in alpha2A and alpha2C adrenergic receptors predispose to hypertension in blacks? Li, J.L., Canham, R.M., Vongpatanasin, W., Leonard, D., Auchus, R.J., Victor, R.G. Hypertension (2006) [Pubmed]
  2. A point mutation of the alpha 2-adrenoceptor that blocks coupling to potassium but not calcium currents. Surprenant, A., Horstman, D.A., Akbarali, H., Limbird, L.E. Science (1992) [Pubmed]
  3. Coupling of a mutated form of the human beta 2-adrenergic receptor to Gi and Gs. Requirement for multiple cytoplasmic domains in the coupling process. Liggett, S.B., Caron, M.G., Lefkowitz, R.J., Hnatowich, M. J. Biol. Chem. (1991) [Pubmed]
  4. Regulation of the alpha 2A-adrenergic receptor in the HT29 cell line. Effects of insulin and growth factors. Devedjian, J.C., Fargues, M., Denis-Pouxviel, C., Daviaud, D., Prats, H., Paris, H. J. Biol. Chem. (1991) [Pubmed]
  5. Further evidence of the involvement of alpha-2A-adrenergic receptor gene (ADRA2A) in inattentive dimensional scores of attention-deficit/hyperactivity disorder. Roman, T., Polanczyk, G.V., Zeni, C., Genro, J.P., Rohde, L.A., Hutz, M.H. Mol. Psychiatry (2006) [Pubmed]
  6. Polymorphism in the promoter region of the alpha 2A adrenergic receptor gene and mood disorders. Ohara, K., Nagai, M., Tani, K., Tsukamoto, T., Suzuki, Y., Ohara, K. Neuroreport (1998) [Pubmed]
  7. The palmitoylated cysteine of the cytoplasmic tail of alpha 2A-adrenergic receptors confers subtype-specific agonist-promoted downregulation. Eason, M.G., Jacinto, M.T., Theiss, C.T., Liggett, S.B. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  8. An asn to lys polymorphism in the third intracellular loop of the human alpha 2A-adrenergic receptor imparts enhanced agonist-promoted Gi coupling. Small, K.M., Forbes, S.L., Brown, K.M., Liggett, S.B. J. Biol. Chem. (2000) [Pubmed]
  9. Four consecutive serines in the third intracellular loop are the sites for beta-adrenergic receptor kinase-mediated phosphorylation and desensitization of the alpha 2A-adrenergic receptor. Eason, M.G., Moreira, S.P., Liggett, S.B. J. Biol. Chem. (1995) [Pubmed]
  10. Distinct pathways of Gi- and Gq-mediated mitogen-activated protein kinase activation. Hawes, B.E., van Biesen, T., Koch, W.J., Luttrell, L.M., Lefkowitz, R.J. J. Biol. Chem. (1995) [Pubmed]
  11. Inhibition of G protein-coupled receptor signaling by expression of cytoplasmic domains of the receptor. Hawes, B.E., Luttrell, L.M., Exum, S.T., Lefkowitz, R.J. J. Biol. Chem. (1994) [Pubmed]
  12. The alpha-2A adrenoceptor agonist guanfacine improves sustained attention and reduces overactivity and impulsiveness in an animal model of Attention-Deficit/Hyperactivity Disorder (ADHD). Sagvolden, T. Behavioral and brain functions : BBF (2006) [Pubmed]
  13. Variations in the alpha2A-adrenergic receptor gene and their functional effects. Kurnik, D., Muszkat, M., Li, C., Sofowora, G.G., Solus, J., Xie, H.G., Harris, P.A., Jiang, L., McMunn, C., Ihrie, P., Dawson, E.P., Williams, S.M., Wood, A.J., Stein, C.M. Clin. Pharmacol. Ther. (2006) [Pubmed]
  14. The alpha 2-adrenergic receptor gene and body fat content and distribution: the HERITAGE Family Study. Garenc, C., Pérusse, L., Chagnon, Y.C., Rankinen, T., Gagnon, J., Borecki, I.B., Leon, A.S., Skinner, J.S., Wilmore, J.H., Rao, D.C., Bouchard, C. Mol. Med. (2002) [Pubmed]
  15. A polymorphism in the alpha2a-adrenoceptor gene and endurance athlete status. Wolfarth, B., Rivera, M.A., Oppert, J.M., Boulay, M.R., Dionne, F.T., Chagnon, M., Gagnon, J., Chagnon, Y., Perusse, L., Keul, J., Bouchard, C. Medicine and science in sports and exercise. (2000) [Pubmed]
  16. Human alpha 2A-adrenergic receptor gene expressed in transgenic mouse adipose tissue under the control of its regulatory elements. Boucher, J., Castan-Laurell, I., Le Lay, S., Grujic, D., Sibrac, D., Krief, S., Lafontan, M., Lowell, B.B., Dugail, I., Saulnier-Blache, J.S., Valet, P. J. Mol. Endocrinol. (2002) [Pubmed]
  17. Neuron specific alpha-adrenergic receptor expression in human cerebellum: implications for emerging cerebellar roles in neurologic disease. Schambra, U.B., Mackensen, G.B., Stafford-Smith, M., Haines, D.E., Schwinn, D.A. Neuroscience (2005) [Pubmed]
  18. Dynamic strength training improves insulin sensitivity and functional balance between adrenergic alpha 2A and beta pathways in subcutaneous adipose tissue of obese subjects. Polak, J., Moro, C., Klimcakova, E., Hejnova, J., Majercik, M., Viguerie, N., Langin, D., Lafontan, M., Stich, V., Berlan, M. Diabetologia (2005) [Pubmed]
  19. Site-directed mutagenesis of alpha 2A-adrenergic receptors: identification of amino acids involved in ligand binding and receptor activation by agonists. Wang, C.D., Buck, M.A., Fraser, C.M. Mol. Pharmacol. (1991) [Pubmed]
  20. Attention-deficit/hyperactivity disorder: advancing on pharmacogenomics. Polanczyk, G., Zeni, C., Genro, J.P., Roman, T., Hutz, M.H., Rohde, L.A. Pharmacogenomics (2005) [Pubmed]
  21. Comparison of ligand binding affinities at human I1-imidazoline binding sites and the high affinity state of alpha-2 adrenoceptor subtypes. Piletz, J.E., Zhu, H., Chikkala, D.N. J. Pharmacol. Exp. Ther. (1996) [Pubmed]
  22. Identification of ADRA2A polymorphisms related to shear-mediated platelet function. Yabe, M., Matsubara, Y., Takahashi, S., Ishihara, H., Shibano, T., Miyaki, K., Omae, K., Watanabe, G., Murata, M., Ikeda, Y. Biochem. Biophys. Res. Commun. (2006) [Pubmed]
  23. A C-1291G polymorphism in the alpha2A-adrenergic receptor gene (ADRA2A) promoter is associated with cortisol escape from dexamethasone and elevated glucose levels. Rosmond, R., Bouchard, C., Björntorp, P. J. Intern. Med. (2002) [Pubmed]
  24. Selective inhibition of adenylyl cyclase by octopamine via a human cloned alpha 2A-adrenoceptor. Airriess, C.N., Rudling, J.E., Midgley, J.M., Evans, P.D. Br. J. Pharmacol. (1997) [Pubmed]
  25. Sites in the third intracellular loop of the alpha 2A-adrenergic receptor confer short term agonist-promoted desensitization. Evidence for a receptor kinase-mediated mechanism. Liggett, S.B., Ostrowski, J., Chesnut, L.C., Kurose, H., Raymond, J.R., Caron, M.G., Lefkowitz, R.J. J. Biol. Chem. (1992) [Pubmed]
  26. Hydrophobicity of residue351 of the G protein Gi1 alpha determines the extent of activation by the alpha 2A-adrenoceptor. Bahia, D.S., Wise, A., Fanelli, F., Lee, M., Rees, S., Milligan, G. Biochemistry (1998) [Pubmed]
  27. Association and linkage of alpha-2A adrenergic receptor gene polymorphisms with childhood ADHD. Park, L., Nigg, J.T., Waldman, I.D., Nummy, K.A., Huang-Pollock, C., Rappley, M., Friderici, K.H. Mol. Psychiatry (2005) [Pubmed]
  28. Detailed physical analysis of a 1.5-megabase YAC contig containing the MXI1 and ADRA2A genes. Manca, A., Volpi, E.V., Laficara, F., Muresu, R., Gray, I.C., Spurr, N.K., Nobile, C. Genomics (1997) [Pubmed]
  29. Haplotype-based analysis of alpha 2A, 2B, and 2C adrenergic receptor genes captures information on common functional loci at each gene. Belfer, I., Buzas, B., Hipp, H., Phillips, G., Taubman, J., Lorincz, I., Evans, C., Lipsky, R.H., Enoch, M.A., Max, M.B., Goldman, D. J. Hum. Genet. (2005) [Pubmed]
  30. Evaluation of the genes for the adrenergic receptors alpha 2A and alpha 1C and Gilles de la Tourette Syndrome. Xu, C., Ozbay, F., Wigg, K., Shulman, R., Tahir, E., Yazgan, Y., Sandor, P., Barr, C.L. Am. J. Med. Genet. B Neuropsychiatr. Genet. (2003) [Pubmed]
  31. Identification of a Gs coupling domain in the amino terminus of the third intracellular loop of the alpha 2A-adrenergic receptor. Evidence for distinct structural determinants that confer Gs versus Gi coupling. Eason, M.G., Liggett, S.B. J. Biol. Chem. (1995) [Pubmed]
  32. Promoter region of the human alpha 2A adrenergic receptor gene. Handy, D.E., Gavras, H. J. Biol. Chem. (1992) [Pubmed]
 
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