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Gene Review

ADRA1A  -  adrenoceptor alpha 1A

Homo sapiens

Synonyms: ADRA1C, ADRA1L1, ALPHA1AAR, Alpha-1A adrenergic receptor, Alpha-1A adrenoceptor, ...
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Disease relevance of ADRA1A


High impact information on ADRA1A

  • A two-allele PstI RFLP for the alpha-1C adrenergic receptor gene (ADRA1C) [5].
  • These results were confirmed by the observation that the C-terminal portion of PLC-beta 1, when co-expressed with the muscarinic acetylcholine receptor type 1 or the alpha 1C-adrenergic receptor in COS-7 cells, markedly inhibited ligand-induced release of inositol phosphates [6].
  • We focused on one alpha(1)-adrenergic subtype, the alpha(1A)-adrenergic receptor, and proposed that genetic variants within the regulatory region of this gene (ADRA1A) alter the expression of this receptor, influencing susceptibility toward schizophrenia [7].
  • Currently, three alpha 1AR subtypes have been characterized both pharmacologically and at the gene level: alpha 1aAR, alpha 1bAR, and alpha 1dAR [8].
  • In several tissues from rat and cloned adrenoceptors, RS-17053 displayed high affinity for the alpha 1A-adrenoceptor (pKi and pA2 estimates of 9.1-9.9) and a 30-100-fold selectivity over the alpha 1B- and the alpha 1D-adrenoceptor subtypes (pK1 and pA2 estimates of 7.7-7.8) [9].

Chemical compound and disease context of ADRA1A


Biological context of ADRA1A


Anatomical context of ADRA1A

  • CONCLUSIONS: To our knowledge, our study represents the first cellular localization of the alpha 1-adrenoceptor subtypes in the human prostate using highly selective alpha 1-adrenoceptor antagonists and is consistent with the physiological observation that the activity of prostatic smooth muscle is mediated by the alpha 1a-adrenoceptor [13].
  • The radioligand binding properties of P2C4 expressed in COS-7 cells were very similar to those of bovine alpha 1C-adrenergic receptor [11].
  • PATIENTS AND METHODS For 254 patients with BPH and/or lower urinary tract symptoms who received alpha(1)-adrenergic antagonists for > or = 3 months, the ADRA1A genotype at position 1475 of the coding region was determined [14].
  • Likewise, the human neuronal SK-N-MC cell line, classically thought to express pharmacological alpha 1AAR and alpha 1BAR subtypes, expresses both alpha 1a/dAR and alpha 1cAR mRNA and no alpha 1bAR mRNA [15].
  • 5. We have found that alpha 1a mRNA is predominant in the human vas deferens, and confirmed that contraction of this organ is mediated by the alpha 1A-adrenoceptor [16].

Associations of ADRA1A with chemical compounds


Other interactions of ADRA1A


Analytical, diagnostic and therapeutic context of ADRA1A


  1. The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype. Forray, C., Bard, J.A., Wetzel, J.M., Chiu, G., Shapiro, E., Tang, R., Lepor, H., Hartig, P.R., Weinshank, R.L., Branchek, T.A. Mol. Pharmacol. (1994) [Pubmed]
  2. Association of alpha1A adrenergic receptor gene variants on chromosome 8p21 with human stage 2 hypertension. Gu, D., Ge, D., Snieder, H., He, J., Chen, S., Huang, J., Li, B., Chen, R., Qiang, B. J. Hypertens. (2006) [Pubmed]
  3. Symptomatic BPH and hypertension: does comorbidity affect quality of life? Man in't Veld, A.J. Eur. Urol. (1998) [Pubmed]
  4. No evidence for association of alpha 1a adrenoceptor gene polymorphism and clozapine-induced urinary incontinence. Hsu, J.W., Wang, Y.C., Lin, C.C., Bai, Y.M., Chen, J.Y., Chiu, H.J., Tsai, S.J., Hong, C.J. Neuropsychobiology (2000) [Pubmed]
  5. A two-allele PstI RFLP for the alpha-1C adrenergic receptor gene (ADRA1C). Hoehe, M.R., Berrettini, W.H., Schwinn, D.A., Hsieh, W.T. Hum. Mol. Genet. (1992) [Pubmed]
  6. Identification of critical regions on phospholipase C-beta 1 required for activation by G-proteins. Wu, D., Jiang, H., Katz, A., Simon, M.I. J. Biol. Chem. (1993) [Pubmed]
  7. Polymorphisms in the promoter region of the alpha1A-adrenoceptor gene are associated with schizophrenia/schizoaffective disorder in a Spanish isolate population. Clark, D.A., Arranz, M.J., Mata, I., Lopéz-Ilundain, J., Pérez-Nievas, F., Kerwin, R.W. Biol. Psychiatry (2005) [Pubmed]
  8. Alpha 1-adrenergic receptor regulation: basic science and clinical implications. Michelotti, G.A., Price, D.T., Schwinn, D.A. Pharmacol. Ther. (2000) [Pubmed]
  9. RS-17053 (N-[2-(2-cyclopropylmethoxyphenoxy)ethyl]-5-chloro-alpha, alpha-dimethyl-1H-indole-3-ethanamine hydrochloride), a selective alpha 1A-adrenoceptor antagonist, displays low affinity for functional alpha 1-adrenoceptors in human prostate: implications for adrenoceptor classification. Ford, A.P., Arredondo, N.F., Blue, D.R., Bonhaus, D.W., Jasper, J., Kava, M.S., Lesnick, J., Pfister, J.R., Shieh, I.A., Vimont, R.L., Williams, T.J., McNeal, J.E., Stamey, T.A., Clarke, D.E. Mol. Pharmacol. (1996) [Pubmed]
  10. Long-term safety and efficacy of tamsulosin for the treatment of lower urinary tract symptoms associated with benign prostatic hyperplasia. Narayan, P., Evans, C.P., Moon, T. J. Urol. (2003) [Pubmed]
  11. Cloning, functional expression and tissue distribution of human cDNA for the alpha 1C-adrenergic receptor. Hirasawa, A., Horie, K., Tanaka, T., Takagaki, K., Murai, M., Yano, J., Tsujimoto, G. Biochem. Biophys. Res. Commun. (1993) [Pubmed]
  12. 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]
  13. Localization of the alpha 1A-adrenoceptor in the human prostate. Lepor, H., Tang, R., Kobayashi, S., Shapiro, E., Forray, C., Wetzel, J.M., Gluchowski, C. J. Urol. (1995) [Pubmed]
  14. Polymorphisms in the alpha1A-adrenoceptor gene do not modify the short- and long-term efficacy of alpha1-adrenoceptor antagonists in the treatment of benign prostatic hyperplasia. Mochtar, C.A., Laan, W., Van Houwelingen, K.P., Franke, B., De La Rosette, J.J., Schalken, J.A., Kiemeney, L.A. BJU international. (2006) [Pubmed]
  15. Expression of alpha 1-adrenergic receptor subtype mRNA in rat tissues and human SK-N-MC neuronal cells: implications for alpha 1-adrenergic receptor subtype classification. Price, D.T., Chari, R.S., Berkowitz, D.E., Meyers, W.C., Schwinn, D.A. Mol. Pharmacol. (1994) [Pubmed]
  16. Quantification and distribution of alpha 1-adrenoceptor subtype mRNAs in human vas deferens: comparison with those of epididymal and pelvic portions. Moriyama, N., Nasu, K., Takeuchi, T., Akiyama, K., Murata, S., Nishimatsu, H., Yano, J., Tsujimoto, G., Kawabe, K. Br. J. Pharmacol. (1997) [Pubmed]
  17. KMD-3213, a novel, potent, alpha 1a-adrenoceptor-selective antagonist: characterization using recombinant human alpha 1-adrenoceptors and native tissues. Shibata, K., Foglar, R., Horie, K., Obika, K., Sakamoto, A., Ogawa, S., Tsujimoto, G. Mol. Pharmacol. (1995) [Pubmed]
  18. Noradrenaline contractions of human prostate mediated by alpha 1A-(alpha 1c-) adrenoceptor subtype. Marshall, I., Burt, R.P., Chapple, C.R. Br. J. Pharmacol. (1995) [Pubmed]
  19. Subtypes of alpha 1-adrenoceptors in hippocampus of pigs, guinea-pigs, calves and humans: regional differences. Hoyer, D., Jones, C.R., Ford, W., Palacios, J.M. Eur. J. Pharmacol. (1990) [Pubmed]
  20. The use of alpha-adrenoceptor antagonists in the pharmacological management of benign prostatic hypertrophy: an overview. Hieble, J.P., Ruffolo, R.R. Pharmacol. Res. (1996) [Pubmed]
  21. Multiple potential regulatory elements in the 5' flanking region of the human alpha 1a-adrenergic receptor. Lee, K., Richardson, C.D., Razik, M.A., Kwatra, M.M., Schwinn, D.A. DNA Seq. (1998) [Pubmed]
  22. Modeling and mutagenesis of the human alpha 1a-adrenoceptor: orientation and function of transmembrane helix V sidechains. Wetzel, J.M., Salon, J.A., Tamm, J.A., Forray, C., Craig, D., Nakanishi, H., Cui, W., Vaysse, P.J., Chiu, G., Weinshank, R.L., Hartig, P.R., Branchek, T.A., Gluchowski, C. Recept. Channels (1996) [Pubmed]
  23. Tamsulosin, the first prostate-selective alpha 1A-adrenoceptor antagonist. A meta-analysis of two randomized, placebo-controlled, multicentre studies in patients with benign prostatic obstruction (symptomatic BPH). European Tamsulosin Study Group. Chapple, C.R., Wyndaele, J.J., Nordling, J., Boeminghaus, F., Ypma, A.F., Abrams, P. Eur. Urol. (1996) [Pubmed]
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