Alpha-2A adrenergic receptor explained

The alpha-2A adrenergic receptor (α_2A adrenoceptor), also known as ADRA2A, is an α₂ adrenergic receptor, and also denotes the human gene encoding it.

Receptor

α₂ adrenergic receptors include 3 highly homologous subtypes: α_2A, α_2B, and α_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 α_2A and α_2C subtypes were required for normal presynaptic control of transmitter release from sympathetic nerves in the heart and from central noradrenergic neurons; the α_2A subtype inhibited transmitter release at high stimulation frequencies, whereas the α_2C subtype modulated neurotransmission at lower levels of nerve activity.^[1]

Gene

This gene encodes α_2A subtype and it contains no introns in either its coding or untranslated sequences.^[2]

Ligands

Agonists

• 4-NEMD
• Brimonidine
• Clonidine
• Detomidine
• Dexmedetomidine
• Guanfacine
• Lofexidine
• Myrcene
  • Medetomidine PS75^[3]
• Tizanidine
• Xylazine

Antagonists

• Atipamezole
• Idazoxan
• 1-PP (active metabolite of buspirone and gepirone)
• Asenapine
• BRL-44408
• Clozapine
• Lurasidone
• Mianserin
• Mirtazapine
• Paliperidone
• Risperidone
• Yohimbine

See also

• Adrenergic receptor

Further reading

• Perälä M, Hirvonen H, Kalimo H, Ala-Uotila S, Regan JW, Akerman KE, Scheinin M . Differential expression of two alpha 2-adrenergic receptor subtype mRNAs in human tissues . Brain Research. Molecular Brain Research . 16 . 1–2 . 57–63 . November 1992 . 1334200 . 10.1016/0169-328X(92)90193-F .
• Surprenant A, Horstman DA, Akbarali H, Limbird LE . A point mutation of the alpha 2-adrenoceptor that blocks coupling to potassium but not calcium currents . Science . 257 . 5072 . 977–980 . August 1992 . 1354394 . 10.1126/science.1354394 . 1992Sci...257..977S .
• Handy DE, Gavras H . Promoter region of the human alpha 2A adrenergic receptor gene . The Journal of Biological Chemistry . 267 . 33 . 24017–24022 . November 1992 . 1385431 . 10.1016/S0021-9258(18)35938-6 . free .
• Suryanarayana S, Daunt DA, Von Zastrow M, Kobilka BK . A point mutation in the seventh hydrophobic domain of the alpha 2 adrenergic receptor increases its affinity for a family of beta receptor antagonists . The Journal of Biological Chemistry . 266 . 23 . 15488–15492 . August 1991 . 1678390 . 10.1016/S0021-9258(18)98642-4 . free .
• Wang CD, Buck MA, Fraser CM . Site-directed mutagenesis of alpha 2A-adrenergic receptors: identification of amino acids involved in ligand binding and receptor activation by agonists . Molecular Pharmacology . 40 . 2 . 168–179 . August 1991 . 1678850 .
• Chhajlani V, Rangel N, Uhlén S, Wikberg JE . Identification of an additional gene belonging to the alpha 2 adrenergic receptor family in the human genome by PCR . FEBS Letters . 280 . 2 . 241–244 . March 1991 . 1849485 . 10.1016/0014-5793(91)80301-I . 26642747 . free . 1991FEBSL.280..241C .
• Guyer CA, Horstman DA, Wilson AL, Clark JD, Cragoe EJ, Limbird LE . Cloning, sequencing, and expression of the gene encoding the porcine alpha 2-adrenergic receptor. Allosteric modulation by Na+, H+, and amiloride analogs . The Journal of Biological Chemistry . 265 . 28 . 17307–17317 . October 1990 . 2170371 . 10.1016/S0021-9258(17)44904-0 . free .
• Fraser CM, Arakawa S, McCombie WR, Venter JC . Cloning, sequence analysis, and permanent expression of a human alpha 2-adrenergic receptor in Chinese hamster ovary cells. Evidence for independent pathways of receptor coupling to adenylate cyclase attenuation and activation . The Journal of Biological Chemistry . 264 . 20 . 11754–11761 . July 1989 . 2568356 . 10.1016/S0021-9258(18)80130-2 . free .
• Kobilka BK, Matsui H, Kobilka TS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ, Regan JW . Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor . Science . 238 . 4827 . 650–656 . October 1987 . 2823383 . 10.1126/science.2823383 . 1987Sci...238..650K .
• Lynch CJ, Steer ML . Evidence for high and low affinity alpha 2-receptors. Comparison of [3H]norepinephrine and [3H]phentolamine binding to human platelet membranes . The Journal of Biological Chemistry . 256 . 7 . 3298–3303 . April 1981 . 6259160 . 10.1016/S0021-9258(19)69606-7 . free .
• Eason MG, Moreira SP, Liggett SB . 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 . The Journal of Biological Chemistry . 270 . 9 . 4681–4688 . March 1995 . 7876239 . 10.1074/jbc.270.9.4681 . free .
• Grassie MA, Milligan G . Analysis of the relative interactions between the alpha 2C10 adrenoceptor and the guanine-nucleotide-binding proteins G(o)1 alpha and Gi 2 alpha following co-expression of these polypeptides in rat 1 fibroblasts . The Biochemical Journal . 306 (Pt 2) . Pt 2 . 525–530 . March 1995 . 7887906 . 1136549 . 10.1042/bj3060525 .
• Shilo L, Sakaue M, Thomas JM, Philip M, Hoffman BB . Enhanced transcription of the human alpha 2A-adrenergic receptor gene by cAMP: evidence for multiple cAMP responsive sequences in the promoter region of this gene . Cellular Signalling . 6 . 1 . 73–82 . January 1994 . 8011430 . 10.1016/0898-6568(94)90062-0 .
• Valet P, Senard JM, Devedjian JC, Planat V, Salomon R, Voisin T, Drean G, Couvineau A, Daviaud D, Denis C . Characterization and distribution of alpha 2-adrenergic receptors in the human intestinal mucosa . The Journal of Clinical Investigation . 91 . 5 . 2049–2057 . May 1993 . 8098045 . 288203 . 10.1172/JCI116427 .
• Alblas J, van Corven EJ, Hordijk PL, Milligan G, Moolenaar WH . Gi-mediated activation of the p21ras-mitogen-activated protein kinase pathway by alpha 2-adrenergic receptors expressed in fibroblasts . The Journal of Biological Chemistry . 268 . 30 . 22235–22238 . October 1993 . 8226727 . 10.1016/S0021-9258(18)41514-1 . free .
• Klein U, Ramirez MT, Kobilka BK, von Zastrow M . A novel interaction between adrenergic receptors and the alpha-subunit of eukaryotic initiation factor 2B . The Journal of Biological Chemistry . 272 . 31 . 19099–19102 . August 1997 . 9235896 . 10.1074/jbc.272.31.19099 . free .
• Bétuing S, Daviaud D, Pagès C, Bonnard E, Valet P, Lafontan M, Saulnier-Blache JS . Gbeta gamma-independent coupling of alpha2-adrenergic receptor to p21(rhoA) in preadipocytes . The Journal of Biological Chemistry . 273 . 25 . 15804–15810 . June 1998 . 9624180 . 10.1074/jbc.273.25.15804 . free .
• Prezeau L, Richman JG, Edwards SW, Limbird LE . The zeta isoform of 14-3-3 proteins interacts with the third intracellular loop of different alpha2-adrenergic receptor subtypes . The Journal of Biological Chemistry . 274 . 19 . 13462–13469 . May 1999 . 10224112 . 10.1074/jbc.274.19.13462 . free .
• Hein L, Altman JD, Kobilka BK . Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission . Nature . 402 . 6758 . 181–184 . November 1999 . 10647009 . 10.1038/46040 . 205047992 . 1999Natur.402..181H .
• Schaak S, Cussac D, Cayla C, Devedjian JC, Guyot R, Paris H, Denis C . Alpha(2) adrenoceptors regulate proliferation of human intestinal epithelial cells . Gut . 47 . 2 . 242–250 . August 2000 . 10896916 . 1728001 . 10.1136/gut.47.2.242 .

External links

• Web site: α_2A-adrenoceptor . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2008-11-25 . 2015-04-02 . https://web.archive.org/web/20150402142451/http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2181 . dead .

Notes and References

1. Hein L, Altman JD, Kobilka BK . Two functionally distinct alpha2-adrenergic receptors regulate sympathetic neurotransmission . Nature . 402 . 6758 . 181–184 . November 1999 . 10647009 . 10.1038/46040 . 205047992 . 1999Natur.402..181H .
2. Web site: Entrez Gene: ADRA2A adrenergic, alpha-2A-, receptor.
3. Fink EA, Xu J, Hübner H, Braz JM, Seemann P, Avet C, Craik V, Weikert D, Schmidt MF, Webb CM, Tolmachova NA, Moroz YS, Huang XP, Kalyanaraman C, Gahbauer S, Chen G, Liu Z, Jacobson MP, Irwin JJ, Bouvier M, Du Y, Shoichet BK, Basbaum AI, Gmeiner P . Structure-based discovery of nonopioid analgesics acting through the α_2A-adrenergic receptor . Science . 377 . 6614 . eabn7065 . September 2022 . 36173843 . 10360211 . 10.1126/science.abn7065 .