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Adenosine A2A receptor

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The adenosine A2A receptor, also known as ADORA2A, is an adenosine receptor, but also denotes the human gene encoding it.[1][2]

Structure[]

This protein is a member of the G protein-coupled receptor (GPCR) family which possess seven transmembrane alpha helices. The crystallographic structure of the adenosine A2A receptor PDB 3EML (see figure to the right) reveals a ligand binding pocket distinct from that of other structurally determined GPCRs (i.e., the beta-2 adrenergic receptor and rhodopsin).[3]

Heteromers[]

The actions of the A2A receptor are complicated by the fact that a variety of functional heteromers composed of a mixture of A2A subunits with subunits from other unrelated G-protein coupled receptors have been found in the brain, adding a further degree of complexity to the role of adenosine in modulation of neuronal activity. Hetereomers consisting of adenosine A1/A2A,[4][5] dopamine D2/A2A[6] and D3/A2A,[7] glutamate mGluR5/A2A[8] and cannabinoid CB1/A2A[9] have all been observed, as well as CB1/A2A/D2 heterotrimers,[10] and the functional significance and endogenous role of these hybrid receptors is still only starting to be unravelled.[11][12][13]

Function[]

The gene encodes a protein which is one of several receptor subtypes for adenosine. The activity of the encoded protein, a G protein-coupled receptor family member, is mediated by G proteins which activate adenylyl cyclase, which induce synthesis of intracellular cAMP. The encoded protein is abundant in basal ganglia, vasculature, T lymphocytes, and platelets and it is a major target of caffeine.[14]

Physiological role[]

As with the A1, the A2A receptors are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow. In addition, A2A receptor can negatively regulate overreactive immune cells, thereby protecting tissues from collateral inflammatory damage.[15]

The A2A receptor is responsible for regulating myocardial blood flow by vasodilating the coronary arteries, which increases blood flow to the myocardium, but may lead to hypotension. Just as in A1 receptors, this normally serves as a protective mechanism, but may be destructive in altered cardiac function.

The A2A receptor is also expressed in the brain, where it has important roles in the regulation of glutamate and dopamine release, making it a potential therapeutic target for the treatment of conditions such as insomnia, pain, depression, drug addiction and Parkinson's disease.[16][17][18][19][20][21][22]

Ligands[]

A number of selective A2A ligands have been developed,[23][24][25][26][27][28][29][30][31][32][33][34] with several possible therapeutic applications.[35][36][37][38][39][40] Older research on adenosine receptor function, and non-selective adenosine receptor antagonists such as aminophylline, focused mainly on the role of adenosine receptors in the heart, and led to several randomized controlled trials using these receptor antagonists to treat bradyasystolic arrest.[41][42][43][44][45][46][47]

However the development of more highly selective A2A ligands has led towards other applications, with the most significant focus of research currently being the potential therapeutic role for A2A antagonists in the treatment of Parkinson's disease.[48][49][50][51]

Agonists[]

  • ATL-146e[52]
  • YT-146 (2-(1-octynyl)adenosine)[53]
  • CGS-21680
  • DPMA (N6-(2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl)adenosine)
  • Regadenoson
  • UK-432,097

Antagonists[]

  • Istradefylline (KW-6002)[54]
  • MSX-3[55]
  • Preladenant (SCH-420,814)[56]
  • SCH-58261[57]
  • SCH-412,348
  • SCH-442,416
  • ST-1535[58]
  • Caffeine
  • VER-6623
  • VER-6947
  • VER-7835
  • Vipadenant (BIIB-014)
  • ZM-241,385

Interactions[]

Adenosine A2A receptor has been shown to interact with Dopamine receptor D2.[59]

See also[]

References[]

  1. ↑ Libert F, Parmentier M, Lefort A, Dinsart C, Van Sande J, Maenhaut C, Simons MJ, Dumont JE, Vassart G (May 1989). Selective amplification and cloning of four new members of the G protein-coupled receptor family. Science 244 (4904): 569–72.
  2. ↑ Libert F, Passage E, Parmentier M, Simons MJ, Vassart G, Mattei MG (September 1991). Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor. Genomics 11 (1): 225–7.
  3. ↑ Jaakola VP, Griffith MT, Hanson MA, Cherezov V, Chien EY, Lane JR, IJzerman AP, Stevens RC (October 2008). The 2.6 Angstrom Crystal Structure of a Human A2A Adenosine Receptor Bound to an Antagonist. Science 322 (5905): 1211–7.
  4. ↑ Ciruela F, Casadó V, Rodrigues RJ, Luján R, Burgueño J, Canals M, Borycz J, Rebola N, Goldberg SR, Mallol J, Cortés A, Canela EI, López-Giménez JF, Milligan G, Lluis C, Cunha RA, Ferré S, Franco R (February 2006). Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers. Journal of Neuroscience 26 (7): 2080–7.
  5. ↑ Ferre S, Ciruela F, Borycz J, Solinas M, Quarta D, Antoniou K, Quiroz C, Justinova Z, Lluis C, Franco R, Goldberg SR (2008). Adenosine A1-A2A receptor heteromers: new targets for caffeine in the brain. Frontiers in Bioscience : a Journal and Virtual Library 13 (13): 2391–9.
  6. ↑ Fuxe K, Ferré S, Canals M, Torvinen M, Terasmaa A, Marcellino D, Goldberg SR, Staines W, Jacobsen KX, Lluis C, Woods AS, Agnati LF, Franco R (2005). Adenosine A2A and dopamine D2 heteromeric receptor complexes and their function. Journal of Molecular Neuroscience : MN 26 (2-3): 209–20.
  7. ↑ Torvinen M, Marcellino D, Canals M, Agnati LF, Lluis C, Franco R, Fuxe K (February 2005). Adenosine A2A receptor and dopamine D3 receptor interactions: evidence of functional A2A/D3 heteromeric complexes. Molecular Pharmacology 67 (2): 400–7.
  8. ↑ Zezula J, Freissmuth M (March 2008). The A(2A)-adenosine receptor: a GPCR with unique features?. British Journal of Pharmacology Suppl 1 (S1): S184–90.
  9. ↑ Ferré S, Goldberg SR, Lluis C, Franco R (2009). Looking for the role of cannabinoid receptor heteromers in striatal function. Neuropharmacology Suppl 1: 226–34.
  10. ↑ Marcellino D, Carriba P, Filip M, Borgkvist A, Frankowska M, Bellido I, Tanganelli S, Müller CE, Fisone G, Lluis C, Agnati LF, Franco R, Fuxe K (April 2008). Antagonistic cannabinoid CB1/dopamine D2 receptor interactions in striatal CB1/D2 heteromers. A combined neurochemical and behavioral analysis. Neuropharmacology 54 (5): 815–23.
  11. ↑ Ferré S, Ciruela F, Quiroz C, Luján R, Popoli P, Cunha RA, Agnati LF, Fuxe K, Woods AS, Lluis C, Franco R (2007). Adenosine receptor heteromers and their integrative role in striatal function. TheScientificWorldJournal 7: 74–85.
  12. ↑ Wardas J (2008). Potential role of adenosine A2A receptors in the treatment of schizophrenia. Frontiers in Bioscience : a Journal and Virtual Library 13 (13): 4071–96.
  13. ↑ Simola N, Morelli M, Pinna A (2008). Adenosine A2A receptor antagonists and Parkinson's disease: state of the art and future directions. Current Pharmaceutical Design 14 (15): 1475–89.
  14. ↑ Entrez Gene: ADORA2A adenosine A2A receptor.
  15. ↑ Ohta A, Sitkovsky M. (2001). Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage.. Nature 414 (6866): 916–20.
  16. ↑ Hack SP, Christie MJ (2003). Adaptations in adenosine signaling in drug dependence: therapeutic implications. Critical Reviews in Neurobiology 15 (3-4): 235–74.
  17. ↑ Morelli M, Di Paolo T, Wardas J, Calon F, Xiao D, Schwarzschild MA (December 2007). Role of adenosine A2A receptors in parkinsonian motor impairment and l-DOPA-induced motor complications. Progress in Neurobiology 83 (5): 293–309.
  18. ↑ Schiffmann SN, Fisone G, Moresco R, Cunha RA, Ferré S (December 2007). Adenosine A2A receptors and basal ganglia physiology. Progress in Neurobiology 83 (5): 277–92.
  19. ↑ Ferré S, Diamond I, Goldberg SR, Yao L, Hourani SM, Huang ZL, Urade Y, Kitchen I (December 2007). Adenosine A2A receptors in ventral striatum, hypothalamus and nociceptive circuitry implications for drug addiction, sleep and pain. Progress in Neurobiology 83 (5): 332–47.
  20. ↑ Brown RM, Short JL (November 2008). Adenosine A(2A) receptors and their role in drug addiction. The Journal of Pharmacy and Pharmacology 60 (11): 1409–30.
  21. ↑ Cunha RA, Ferré S, Vaugeois JM, Chen JF (2008). Potential therapeutic interest of adenosine A2A receptors in psychiatric disorders. Current Pharmaceutical Design 14 (15): 1512–24.
  22. ↑ Mingote S, Font L, Farrar AM, Vontell R, Worden LT, Stopper CM, Port RG, Sink KS, Bunce JG, Chrobak JJ, Salamone JD (September 2008). Nucleus accumbens adenosine A2A receptors regulate exertion of effort by acting on the ventral striatopallidal pathway. Journal of Neuroscience 28 (36): 9037–46.
  23. ↑ Ongini E, Monopoli A, Cacciari B, Baraldi PG (2001). Selective adenosine A2A receptor antagonists. Farmaco (Società Chimica Italiana : 1989) 56 (1-2): 87–90.
  24. ↑ Baraldi PG, Cacciari B, Romagnoli R, Spalluto G, Monopoli A, Ongini E, Varani K, Borea PA (January 2002). 7-Substituted 5-amino-2-(2-furyl)pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as A2A adenosine receptor antagonists: a study on the importance of modifications at the side chain on the activity and solubility. Journal of Medicinal Chemistry 45 (1): 115–26.
  25. ↑ Baraldi PG, Fruttarolo F, Tabrizi MA, Preti D, Romagnoli R, El-Kashef H, Moorman A, Varani K, Gessi S, Merighi S, Borea PA (March 2003). Design, synthesis, and biological evaluation of C9- and C2-substituted pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines as new A2A and A3 adenosine receptors antagonists. Journal of Medicinal Chemistry 46 (7): 1229–41.
  26. ↑ Weiss SM, Benwell K, Cliffe IA, Gillespie RJ, Knight AR, Lerpiniere J, Misra A, Pratt RM, Revell D, Upton R, Dourish CT (December 2003). Discovery of nonxanthine adenosine A2A receptor antagonists for the treatment of Parkinson's disease. Neurology 61 (11 Suppl 6): S101–6.
  27. ↑ Cristalli G, Lambertucci C, Taffi S, Vittori S, Volpini R (2003). Medicinal chemistry of adenosine A2A receptor agonists. Current Topics in Medicinal Chemistry 3 (4): 387–401.
  28. ↑ Cacciari B, Pastorin G, Spalluto G (2003). Medicinal chemistry of A2A adenosine receptor antagonists. Current Topics in Medicinal Chemistry 3 (4): 403–11.
  29. ↑ Cristalli G, Cacciari B, Dal Ben D, Lambertucci C, Moro S, Spalluto G, Volpini R (March 2007). Highlights on the development of A(2A) adenosine receptor agonists and antagonists. ChemMedChem 2 (3): 260–81.
  30. ↑ Diniz C, Borges F, Santana L, Uriarte E, Oliveira JM, Gonçalves J, Fresco P (2008). Ligands and therapeutic perspectives of adenosine A(2A) receptors. Current Pharmaceutical Design 14 (17): 1698–722.
  31. ↑ Cristalli G, Lambertucci C, Marucci G, Volpini R, Dal Ben D (2008). A2A adenosine receptor and its modulators: overview on a druggable GPCR and on structure-activity relationship analysis and binding requirements of agonists and antagonists. Current Pharmaceutical Design 14 (15): 1525–52.
  32. ↑ Gillespie RJ, Adams DR, Bebbington D, Benwell K, Cliffe IA, Dawson CE, Dourish CT, Fletcher A, Gaur S, Giles PR, Jordan AM, Knight AR, Knutsen LJ, Lawrence A, Lerpiniere J, Misra A, Porter RH, Pratt RM, Shepherd R, Upton R, Ward SE, Weiss SM, Williamson DS (May 2008). Antagonists of the human adenosine A2A receptor. Part 1: Discovery and synthesis of thieno[3,2-d]pyrimidine-4-methanone derivatives. Bioorganic & Medicinal Chemistry Letters 18 (9): 2916–9.
  33. ↑ Gillespie RJ, Cliffe IA, Dawson CE, Dourish CT, Gaur S, Giles PR, Jordan AM, Knight AR, Lawrence A, Lerpiniere J, Misra A, Pratt RM, Todd RS, Upton R, Weiss SM, Williamson DS (May 2008). Antagonists of the human adenosine A2A receptor. Part 2: Design and synthesis of 4-arylthieno[3,2-d]pyrimidine derivatives. Bioorganic & Medicinal Chemistry Letters 18 (9): 2920–3.
  34. ↑ Gillespie RJ, Cliffe IA, Dawson CE, Dourish CT, Gaur S, Jordan AM, Knight AR, Lerpiniere J, Misra A, Pratt RM, Roffey J, Stratton GC, Upton R, Weiss SM, Williamson DS (May 2008). Antagonists of the human adenosine A2A receptor. Part 3: Design and synthesis of pyrazolo[3,4-d]pyrimidines, pyrrolo[2,3-d]pyrimidines and 6-arylpurines. Bioorganic & Medicinal Chemistry Letters 18 (9): 2924–9.
  35. ↑ Sullivan GW (November 2003). Adenosine A2A receptor agonists as anti-inflammatory agents. Current Opinion in Investigational Drugs (London, England : 2000) 4 (11): 1313–9.
  36. ↑ Lappas CM, Sullivan GW, Linden J (July 2005). Adenosine A2A agonists in development for the treatment of inflammation. Expert Opinion on Investigational Drugs 14 (7): 797–806.
  37. ↑ El Yacoubi M, Costentin J, Vaugeois JM (December 2003). Adenosine A2A receptors and depression. Neurology 61 (11 Suppl 6): S82–7.
  38. ↑ Kaster MP, Rosa AO, Rosso MM, Goulart EC, Santos AR, Rodrigues AL (January 2004). Adenosine administration produces an antidepressant-like effect in mice: evidence for the involvement of A1 and A2A receptors. Neuroscience Letters 355 (1-2): 21–4.
  39. ↑ Takahashi RN, Pamplona FA, Prediger RD (2008). Adenosine receptor antagonists for cognitive dysfunction: a review of animal studies. Frontiers in Bioscience : a Journal and Virtual Library 13 (13): 2614–32.
  40. ↑ Lobato KR, Binfaré RW, Budni J, Rosa AO, Santos AR, Rodrigues AL (May 2008). Involvement of the adenosine A1 and A2A receptors in the antidepressant-like effect of zinc in the forced swimming test. Progress in Neuro-psychopharmacology & Biological Psychiatry 32 (4): 994–9.
  41. ↑ Burton JH, Mass M, Menegazzi JJ, Yealy DM (1997). Aminophylline as an adjunct to standard advanced cardiac life support in prolonged cardiac arrest. Annals of emergency medicine 30 (2): 154–8.
  42. ↑ Khoury MY, Moukarbel GV, Obeid MY, Alam SE (2001). Effect of aminophylline on complete atrioventricular block with ventricular asystole following blunt chest trauma. Injury 32 (4): 335–8.
  43. ↑ Mader TJ, Bertolet B, Ornato JP, Gutterman JM (2000). Aminophylline in the treatment of atropine-resistant bradyasystole. Resuscitation 47 (2): 105–12.
  44. ↑ Mader TJ, Smithline HA, Durkin L, Scriver G (2003). A randomized controlled trial of intravenous aminophylline for atropine-resistant out-of-hospital asystolic cardiac arrest. Academic Emergency Medicine 10 (3): 192–7.
  45. ↑ Mader TJ, Gibson P (1997). Adenosine receptor antagonism in refractory asystolic cardiac arrest: results of a human pilot study. Resuscitation 35 (1): 3–7.
  46. ↑ Perouansky M, Shamir M, Hershkowitz E, Donchin Y (1998). Successful resuscitation using aminophylline in refractory cardiac arrest with asystole. Resuscitation 38 (1): 39–41.
  47. ↑ Viskin S, Belhassen B, Roth A, Reicher M, Averbuch M, Sheps D, Shalabye E, Laniado S (1993). Aminophylline for bradyasystolic cardiac arrest refractory to atropine and epinephrine. Ann. Intern. Med. 118 (4): 279–81.
  48. ↑ Jenner P (December 2003). A2A antagonists as novel non-dopaminergic therapy for motor dysfunction in PD. Neurology 61 (11 Suppl 6): S32–8.
  49. ↑ Mori A, Shindou T (December 2003). Modulation of GABAergic transmission in the striatopallidal system by adenosine A2A receptors: a potential mechanism for the antiparkinsonian effects of A2A antagonists. Neurology 61 (11 Suppl 6): S44–8.
  50. ↑ Pinna A, Wardas J, Simola N, Morelli M (November 2005). New therapies for the treatment of Parkinson's disease: adenosine A2A receptor antagonists. Life Sciences 77 (26): 3259–67.
  51. ↑ Kelsey JE, Langelier NA, Oriel BS, Reedy C (January 2009). The effects of systemic, intrastriatal, and intrapallidal injections of caffeine and systemic injections of A2A and A1 antagonists on forepaw stepping in the unilateral 6-OHDA-lesioned rat. Psychopharmacology 201 (4): 529–39.
  52. ↑ Jacobson KA, Gao ZG (2006). Adenosine receptors as therapeutic targets. Nature reviews. Drug discovery 5 (3): 247–64.
  53. ↑ Yoneyama F, Yamada H, Satoh K, Taira N (March 1992). Vasodepressor mechanisms of 2-(1-octynyl)-adenosine (YT-146), a selective adenosine A2 receptor agonist, involve the opening of glibenclamide-sensitive K+ channels. Eur. J. Pharmacol. 213 (2): 199–204.
  54. ↑ Kase H, Aoyama S, Ichimura M, Ikeda K, Ishii A, Kanda T, Koga K, Koike N, Kurokawa M, Kuwana Y, Mori A, Nakamura J, Nonaka H, Ochi M, Saki M, Shimada J, Shindou T, Shiozaki S, Suzuki F, Takeda M, Yanagawa K, Richardson PJ, Jenner P, Bedard P, Borrelli E, Hauser RA, Chase TN (December 2003). Progress in pursuit of therapeutic A2A antagonists: the adenosine A2A receptor selective antagonist KW6002: research and development toward a novel nondopaminergic therapy for Parkinson's disease. Neurology 61 (11 Suppl 6): S97–100.
  55. ↑ Mott AM, Nunes EJ, Collins LE, Port RG, Sink KS, Hockemeyer J, Müller CE, Salamone JD (January 2009). The adenosine A(2A) antagonist MSX-3 reverses the effects of the dopamine antagonist haloperidol on effort-related decision making in a T-maze cost/benefit procedure. Psychopharmacology 204 (1): 103–12.
  56. ↑ Hodgson RA, Bertorelli R, Varty GB, Lachowicz JE, Forlani A, Fredduzzi S, Cohen-Williams ME, Higgins GA, Impagnatiello F, Nicolussi E, Parra LE, Foster C, Zhai Y, Neustadt BR, Stamford AW, Parker EM, Reggiani A, Hunter JC (March 2009). Characterization of the Potent and Highly Selective A2A Receptor Antagonists Preladenant and SCH 412348 in Rodent Models of Movement Disorders and Depression. The Journal of Pharmacology and Experimental Therapeutics 330 (1): 294–303.
  57. ↑ Pinna A, Fenu S, Morelli M (March 2001). Motor stimulant effects of the adenosine A2A receptor antagonist SCH 58261 do not develop tolerance after repeated treatments in 6-hydroxydopamine-lesioned rats. Synapse 39 (3): 233–8.
  58. ↑ Rose S, Jackson MJ, Smith LA, Stockwell K, Johnson L, Carminati P, Jenner P (September 2006). The novel adenosine A2a receptor antagonist ST1535 potentiates the effects of a threshold dose of L-DOPA in MPTP treated common marmosets. European Journal of Pharmacology 546 (1-3): 82–7.
  59. ↑ Kamiya, Toshio, Saitoh Osamu, Yoshioka Kazuaki, Nakata Hiroyasu (Jun. 2003). Oligomerization of adenosine A2A and dopamine D2 receptors in living cells. Biochem. Biophys. Res. Commun. 306 (2): 544–9.

Further reading[]


  • Ongini E, Adami M, Ferri C, Bertorelli R (1997). Adenosine A2A receptors and neuroprotection.. Ann. N. Y. Acad. Sci. 825 (1 Neuroprotecti): 30–48.
  • Furlong TJ, Pierce KD, Selbie LA, Shine J (1992). Molecular characterization of a human brain adenosine A2 receptor.. Brain Res. Mol. Brain Res. 15 (1-2): 62–6.
  • Makujina SR, Sabouni MH, Bhatia S, et al. (1992). Vasodilatory effects of adenosine A2 receptor agonists CGS 21680 and CGS 22492 in human vasculature.. Eur. J. Pharmacol. 221 (2-3): 243–7.
  • Karlsten R, Gordh T, Post C (1992). Local antinociceptive and hyperalgesic effects in the formalin test after peripheral administration of adenosine analogues in mice.. Pharmacol. Toxicol. 70 (6 Pt 1): 434–8.
  • Libert F, Passage E, Parmentier M, et al. (1992). Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor.. Genomics 11 (1): 225–7.
  • Martinez-Mir MI, Probst A, Palacios JM (1992). Adenosine A2 receptors: selective localization in the human basal ganglia and alterations with disease.. Neuroscience 42 (3): 697–706.
  • Libert F, Parmentier M, Lefort A, et al. (1989). Selective amplification and cloning of four new members of the G protein-coupled receptor family.. Science 244 (4904): 569–72.
  • Kim J, Wess J, van Rhee AM, et al. (1995). Site-directed mutagenesis identifies residues involved in ligand recognition in the human A2A adenosine receptor.. J. Biol. Chem. 270 (23): 13987–97.
  • Szondy Z (1995). Adenosine stimulates DNA fragmentation in human thymocytes by Ca(2+)-mediated mechanisms.. Biochem. J. ( Pt 3): 877–85.
  • MacCollin M, Peterfreund R, MacDonald M, et al. (1994). Mapping of a human A2A adenosine receptor (ADORA2) to chromosome 22.. Genomics 20 (2): 332–3.
  • Nonaka H, Ichimura M, Takeda M, et al. (1994). KF17837 ((E)-8-(3,4-dimethoxystyryl)-1,3-dipropyl-7-methylxanthine), a potent and selective adenosine A2 receptor antagonist.. Eur. J. Pharmacol. 267 (3): 335–41.
  • Iwamoto T, Umemura S, Toya Y, et al. (1994). Identification of adenosine A2 receptor-cAMP system in human aortic endothelial cells.. Biochem. Biophys. Res. Commun. 199 (2): 905–10.
  • Salmon JE, Brogle N, Brownlie C, et al. (1993). Human mononuclear phagocytes express adenosine A1 receptors. A novel mechanism for differential regulation of Fc gamma receptor function.. J. Immunol. 151 (5): 2775–85.
  • Peterfreund RA, MacCollin M, Gusella J, Fink JS (1996). Characterization and expression of the human A2A adenosine receptor gene.. J. Neurochem. 66 (1): 362–8.
  • Le F, Townsend-Nicholson A, Baker E, et al. (1996). Characterization and chromosomal localization of the human A2A adenosine receptor gene: ADORA2A.. Biochem. Biophys. Res. Commun. 223 (2): 461–7.
  • Jiang Q, Van Rhee AM, Kim J, et al. (1996). Hydrophilic side chains in the third and seventh transmembrane helical domains of human A2A adenosine receptors are required for ligand recognition.. Mol. Pharmacol. 50 (3): 512–21.
  • Ledent C, Vaugeois JM, Schiffmann SN, et al. (1997). Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2A receptor.. Nature 388 (6643): 674–8.
  • Koshiba M, Rosin DL, Hayashi N, et al. (1999). Patterns of A2A extracellular adenosine receptor expression in different functional subsets of human peripheral T cells. Flow cytometry studies with anti-A2A receptor monoclonal antibodies.. Mol. Pharmacol. 55 (3): 614–24.
  • Borgland SL, Castañón M, Spevak W, Parkinson FE (1999). Effects of propentofylline on adenosine receptor activity in Chinese hamster ovary cell lines transfected with human A1, A2A, or A2B receptors and a luciferase reporter gene.. Can. J. Physiol. Pharmacol. 76 (12): 1132–8.



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