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Gene Review

Adra2a  -  adrenergic receptor, alpha 2a

Mus musculus

Synonyms: AW122659, Adra-2, Adra-2a, Alpha-2A adrenergic receptor, Alpha-2A adrenoceptor, ...
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Disease relevance of Adra2a


Psychiatry related information on Adra2a

  • This detrimental effect was prevented by pretreatment with the alpha2-antagonist yohimbine (1-3 mg kg(-1) i.p.) and by the alpha2A-antagonist BRL-44408 (0.3-1 mg kg(-1) i.p.). By contrast, the alpha(2B,C) antagonists ARC-239 (10 mg kg(-1) i.p.) and prazosin (1 mg kg(-1) i.p.) did not revert the amnesia induced by both clonidine and guanabenz [6].

High impact information on Adra2a


Biological context of Adra2a

  • The alpha 2AAR subtype appears to mediate reduction in blood pressure following alpha 2A agonist administration as well as sedative, anesthetic-sparing, and analgesic responses to alpha 2AAR agonists [9].
  • Distribution of mRNA encoding three alpha 2-adrenergic receptor subtypes in the developing mouse embryo suggests a role for the alpha 2A subtype in apoptosis [10].
  • Although the spatial expression of the transgene in the adult brain often overlaps that for the endogenous alpha 2A adrenergic receptor, both ectopic expression and the absence of appropriate expression were noted; in contrast five of the six lines show temporal expression characteristic of the endogenous alpha 2A adrenergic receptor gene [11].
  • The alpha-subunit of eukaryotic initiation factor 2B (eIF-2B), a guanine nucleotide exchange protein that functions in regulation of translation, was observed to associate with the carboxyl-terminal cytoplasmic domains of the alpha2A- and alpha2B-adrenergic receptors in a yeast two-hybrid screen of a cDNA library prepared from 293 cells [12].
  • Activation and deactivation kinetics of alpha 2A- and alpha 2C-adrenergic receptor-activated G protein-activated inwardly rectifying K+ channel currents [13].

Anatomical context of Adra2a


Associations of Adra2a with chemical compounds

  • We conclude that chloroethylclonidine binds to all major alpha-adrenoceptor subtypes and irreversibly inactivates not only alpha 1B-adrenoceptors but also alpha 2A- and alpha 2C-adrenoceptors, whereas alpha 1A- and alpha 2B-adrenoceptors are relatively resistant to its alkylating action, although they can bind chloroethylclonidine [14].
  • Previous studies demonstrated that mutation of a conserved aspartate residue in the alpha 2AAR to asparagine (D79N alpha 2AAR) resulted in a receptor that retained its ability to inhibit voltage-gated Ca2+ channels and cAMP production but was unable to activate K+ currents in AtT20 cells (Surprenant et al., 1992) [9].
  • RESULTS: In vivo, loss and recovery of the righting reflex required similar times after intraperitoneal injection of etomidate in wild-type and in alpha2A-receptor-deficient mice, indicating that the hypnotic effect of etomidate in mice does not require the alpha2A-receptor subtype [16].
  • Little autoinhibition by released noradrenaline in trains of pulses remains when the alpha2 A/D-adrenoceptor is lacking, again in accord with a predominance of alpha2 A/D-autoreceptors [17].
  • Dexmedetomidine produces its neuroprotective effect via the alpha 2A-adrenoceptor subtype [18].

Regulatory relationships of Adra2a


Other interactions of Adra2a


Analytical, diagnostic and therapeutic context of Adra2a


  1. Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission. Hein, L., Altman, J.D., Kobilka, B.K. Nature (1999) [Pubmed]
  2. Alpha2-adrenoceptor-mediated inhibition of cultured sympathetic neurons: changes in alpha2A/D-adrenoceptor-deficient mice. Trendelenburg, A.U., Nörenberg, W., Hein, L., Meyer, A., Starke, K. Naunyn Schmiedebergs Arch. Pharmacol. (2001) [Pubmed]
  3. Evaluation of the alpha2C-adrenoceptor as a neuropsychiatric drug target studies in transgenic mouse models. Scheinin, M., Sallinen, J., Haapalinna, A. Life Sci. (2001) [Pubmed]
  4. Feedback inhibition of catecholamine release by two different alpha2-adrenoceptor subtypes prevents progression of heart failure. Brede, M., Wiesmann, F., Jahns, R., Hadamek, K., Arnolt, C., Neubauer, S., Lohse, M.J., Hein, L. Circulation (2002) [Pubmed]
  5. Reduced thrombus stability in mice lacking the alpha2A-adrenergic receptor. Pozgajová, M., Sachs, U.J., Hein, L., Nieswandt, B. Blood (2006) [Pubmed]
  6. Alpha-2 agonist-induced memory impairment is mediated by the alpha-2A-adrenoceptor subtype. Galeotti, N., Bartolini, A., Ghelardini, C. Behav. Brain Res. (2004) [Pubmed]
  7. Different structural constraints for recognition of mouse H-2Kd and -Kk antigens by alloimmune cytolytic T lymphocytes. Schøller, J., Shimonkevitz, R., MacDonald, H.R., Kvist, S. J. Exp. Med. (1986) [Pubmed]
  8. A point mutation (D79N) of the alpha2A adrenergic receptor abolishes the antiepileptogenic action of endogenous norepinephrine. Janumpalli, S., Butler, L.S., MacMillan, L.B., Limbird, L.E., McNamara, J.O. J. Neurosci. (1998) [Pubmed]
  9. Alpha 2-adrenergic receptor subtypes: subtle mutation of the alpha 2A-adrenergic receptor in vivo by gene targeting strategies reveals the role of this subtype in multiple physiological settings. MacMillan, L.B., Lakhlani, P., Lovinger, D., Limbird, L.E. Recent Prog. Horm. Res. (1998) [Pubmed]
  10. Distribution of mRNA encoding three alpha 2-adrenergic receptor subtypes in the developing mouse embryo suggests a role for the alpha 2A subtype in apoptosis. Wang, R.X., Limbird, L.E. Mol. Pharmacol. (1997) [Pubmed]
  11. Expression of alpha 2-adrenergic receptor subtypes in the mouse brain: evaluation of spatial and temporal information imparted by 3 kb of 5' regulatory sequence for the alpha 2A AR-receptor gene in transgenic animals. Wang, R., Macmillan, L.B., Fremeau, R.T., Magnuson, M.A., Lindner, J., Limbird, L.E. Neuroscience (1996) [Pubmed]
  12. A novel interaction between adrenergic receptors and the alpha-subunit of eukaryotic initiation factor 2B. Klein, U., Ramirez, M.T., Kobilka, B.K., von Zastrow, M. J. Biol. Chem. (1997) [Pubmed]
  13. Activation and deactivation kinetics of alpha 2A- and alpha 2C-adrenergic receptor-activated G protein-activated inwardly rectifying K+ channel currents. Bünemann, M., Bücheler, M.M., Philipp, M., Lohse, M.J., Hein, L. J. Biol. Chem. (2001) [Pubmed]
  14. Selective irreversible binding of chloroethylclonidine at alpha 1- and alpha 2-adrenoceptor subtypes. Michel, M.C., Kerker, J., Branchek, T.A., Forray, C. Mol. Pharmacol. (1993) [Pubmed]
  15. Abnormal regulation of the sympathetic nervous system in alpha2A-adrenergic receptor knockout mice. Altman, J.D., Trendelenburg, A.U., MacMillan, L., Bernstein, D., Limbird, L., Starke, K., Kobilka, B.K., Hein, L. Mol. Pharmacol. (1999) [Pubmed]
  16. Activation of alpha 2B-adrenoceptors mediates the cardiovascular effects of etomidate. Paris, A., Philipp, M., Tonner, P.H., Steinfath, M., Lohse, M., Scholz, J., Hein, L. Anesthesiology (2003) [Pubmed]
  17. Occurrence, pharmacology and function of presynaptic alpha2-autoreceptors in alpha2A/D-adrenoceptor-deficient mice. Trendelenburg, A.U., Hein, L., Gaiser, E.G., Starke, K. Naunyn Schmiedebergs Arch. Pharmacol. (1999) [Pubmed]
  18. Dexmedetomidine produces its neuroprotective effect via the alpha 2A-adrenoceptor subtype. Ma, D., Hossain, M., Rajakumaraswamy, N., Arshad, M., Sanders, R.D., Franks, N.P., Maze, M. Eur. J. Pharmacol. (2004) [Pubmed]
  19. Gene substitution/knockout to delineate the role of alpha 2-adrenoceptor subtypes in mediating central effects of catecholamines and imidazolines. Hein, L., Limbird, L.E., Eglen, R.M., Kobilka, B.K. Ann. N. Y. Acad. Sci. (1999) [Pubmed]
  20. Norepinephrine transporter knockout-induced up-regulation of brain alpha2A/C-adrenergic receptors. Gilsbach, R., Faron-Górecka, A., Rogóz, Z., Brüss, M., Caron, M.G., Dziedzicka-Wasylewska, M., Bönisch, H. J. Neurochem. (2006) [Pubmed]
  21. Targeted inactivation of the gene encoding the mouse alpha 2c-adrenoceptor homolog. Link, R.E., Stevens, M.S., Kulatunga, M., Scheinin, M., Barsh, G.S., Kobilka, B.K. Mol. Pharmacol. (1995) [Pubmed]
  22. Alpha 2-adrenergic agonist enrichment of spinophilin at the cell surface involves beta gamma subunits of Gi proteins and is preferentially induced by the alpha 2A-subtype. Brady, A.E., Wang, Q., Allen, P.B., Rizzo, M., Greengard, P., Limbird, L.E. Mol. Pharmacol. (2005) [Pubmed]
  23. Direct effects of testosterone, 17 beta-estradiol, and progesterone on adrenergic regulation in cultured brown adipocytes: potential mechanism for gender-dependent thermogenesis. Monjo, M., Rodríguez, A.M., Palou, A., Roca, P. Endocrinology (2003) [Pubmed]
  24. Genomic organization of adrenergic and serotonin receptors in the mouse: linkage mapping of sequence-related genes provides a method for examining mammalian chromosome evolution. Oakey, R.J., Caron, M.G., Lefkowitz, R.J., Seldin, M.F. Genomics (1991) [Pubmed]
  25. Substitution of a mutant alpha2a-adrenergic receptor via "hit and run" gene targeting reveals the role of this subtype in sedative, analgesic, and anesthetic-sparing responses in vivo. Lakhlani, P.P., MacMillan, L.B., Guo, T.Z., McCool, B.A., Lovinger, D.M., Maze, M., Limbird, L.E. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
  26. The second intracellular loop of the alpha2-adrenergic receptors determines subtype-specific coupling to cAMP production. Näsman, J., Jansson, C.C., Akerman, K.E. J. Biol. Chem. (1997) [Pubmed]
  27. Transcutaneous electrical nerve stimulation activates peripherally located alpha-2A adrenergic receptors. King, E.W., Audette, K., Athman, G.A., Nguyen, H.O., Sluka, K.A., Fairbanks, C.A. Pain (2005) [Pubmed]
  28. Alternative splicing generates two isoforms of the alpha 2 subunit of the inhibitory glycine receptor. Kuhse, J., Kuryatov, A., Maulet, Y., Malosio, M.L., Schmieden, V., Betz, H. FEBS Lett. (1991) [Pubmed]
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