Adenosine A2A receptor

Adenosine A2a receptor
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols ADORA2A ; A2aR; ADORA2; RDC8
External IDs OMIM: 102776 MGI: 99402 HomoloGene: 20166 IUPHAR: 19 ChEMBL: 251 GeneCards: ADORA2A Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 135 11540
Ensembl ENSG00000128271 ENSMUSG00000020178
UniProt P29274 Q60613
RefSeq (mRNA) NM_000675 NM_009630
RefSeq (protein) NP_000666 NP_033760
Location (UCSC) Chr 22:
24.42 – 24.44 Mb		 Chr 10:
75.32 – 75.33 Mb
PubMed search

The adenosine A2A receptor, also known as ADORA2A, is an adenosine receptor, and 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 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. Heteromers 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]

The receptor's role in immunomodulation in the context of cancer has suggested that it is an important immune checkpoint molecule.[14]

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, which is a competitive antagonist of this protein.[15]

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.[16]

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.[17][18][19][20][21][22][23]

Ligands

A number of selective A2A ligands have been developed,[24][25][26][27][28][29][30][31][32][33][34][35] with several possible therapeutic applications.[36][37][38][39][40][41] 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.[42][43][44][45][46][47][48]

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.[49][50][51][52]

Agonists

Antagonists

Interactions

Adenosine A2A receptor has been shown to interact with Dopamine receptor D2.[61] As a result, Adenosine receptor A2A decreases activity in the Dopamine D2 receptors.

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. doi:10.1126/science.2541503. PMID 2541503.
  2. ↑ Libert F, Passage E, Parmentier M, Simons MJ, Vassart G, Mattei MG (Sep 1991). "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics 11 (1): 225–7. doi:10.1016/0888-7543(91)90125-X. PMID 1662665.
  3. ↑ PDB: 3EML​; Jaakola VP, Griffith MT, Hanson MA, Cherezov V, Chien EY, Lane JR, Ijzerman AP, Stevens RC (Nov 2008). "The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist". Science 322 (5905): 1211–7. doi:10.1126/science.1164772. PMC 2586971. PMID 18832607.
  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 (Feb 2006). "Presynaptic control of striatal glutamatergic neurotransmission by adenosine A1-A2A receptor heteromers". The Journal of Neuroscience 26 (7): 2080–7. doi:10.1523/JNEUROSCI.3574-05.2006. PMID 16481441.
  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 13 (13): 2391–9. doi:10.2741/2852. PMID 17981720.
  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. doi:10.1385/JMN:26:2-3:209. PMID 16012194.
  7. ↑ Torvinen M, Marcellino D, Canals M, Agnati LF, Lluis C, Franco R, Fuxe K (Feb 2005). "Adenosine A2A receptor and dopamine D3 receptor interactions: evidence of functional A2A/D3 heteromeric complexes". Molecular Pharmacology 67 (2): 400–7. doi:10.1124/mol.104.003376. PMID 15539641.
  8. ↑ Zezula J, Freissmuth M (Mar 2008). "The A(2A)-adenosine receptor: a GPCR with unique features?". British Journal of Pharmacology. 153 Suppl 1 (S1): S184–90. doi:10.1038/sj.bjp.0707674. PMC 2268059. PMID 18246094.
  9. ↑ Ferré S, Goldberg SR, Lluis C, Franco R (2009). "Looking for the role of cannabinoid receptor heteromers in striatal function". Neuropharmacology. 56 Suppl 1 (Suppl 1): 226–34. doi:10.1016/j.neuropharm.2008.06.076. PMC 2635338. PMID 18691604.
  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 (Apr 2008). "Antagonistic cannabinoid CB1/dopamine D2 receptor interactions in striatal CB1/D2 heteromers. A combined neurochemical and behavioral analysis". Neuropharmacology 54 (5): 815–23. doi:10.1016/j.neuropharm.2007.12.011. PMID 18262573.
  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. doi:10.1100/tsw.2007.211. PMID 17982579.
  12. ↑ Wardas J (2008). "Potential role of adenosine A2A receptors in the treatment of schizophrenia". Frontiers in Bioscience 13 (13): 4071–96. doi:10.2741/2995. PMID 18508501.
  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. doi:10.2174/138161208784480072. PMID 18537671.
  14. ↑ Cekic C, Linden J (Dec 2014). "Adenosine A2A receptors intrinsically regulate CD8+ T cells in the tumor microenvironment". Cancer Research 74 (24): 7239–49. doi:10.1158/0008-5472.CAN-13-3581. PMID 25341542.
  15. ↑ "Entrez Gene: ADORA2A adenosine A2A receptor".
  16. ↑ 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. doi:10.1038/414916a. PMID 11780065.
  17. ↑ Hack SP, Christie MJ (2003). "Adaptations in adenosine signaling in drug dependence: therapeutic implications". Critical Reviews in Neurobiology 15 (3-4): 235–74. doi:10.1615/CritRevNeurobiol.v15.i34.30. PMID 15248812.
  18. ↑ Morelli M, Di Paolo T, Wardas J, Calon F, Xiao D, Schwarzschild MA (Dec 2007). "Role of adenosine A2A receptors in parkinsonian motor impairment and l-DOPA-induced motor complications". Progress in Neurobiology 83 (5): 293–309. doi:10.1016/j.pneurobio.2007.07.001. PMID 17826884.
  19. ↑ Schiffmann SN, Fisone G, Moresco R, Cunha RA, Ferré S (Dec 2007). "Adenosine A2A receptors and basal ganglia physiology". Progress in Neurobiology 83 (5): 277–92. doi:10.1016/j.pneurobio.2007.05.001. PMC 2148496. PMID 17646043.
  20. ↑ Ferré S, Diamond I, Goldberg SR, Yao L, Hourani SM, Huang ZL, Urade Y, Kitchen I (Dec 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. doi:10.1016/j.pneurobio.2007.04.002. PMC 2141681. PMID 17532111.
  21. ↑ Brown RM, Short JL (Nov 2008). "Adenosine A(2A) receptors and their role in drug addiction". The Journal of Pharmacy and Pharmacology 60 (11): 1409–30. doi:10.1211/jpp/60.11.0001. PMID 18957161.
  22. ↑ 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. doi:10.2174/138161208784480090. PMC 2423946. PMID 18537674.
  23. ↑ Mingote S, Font L, Farrar AM, Vontell R, Worden LT, Stopper CM, Port RG, Sink KS, Bunce JG, Chrobak JJ, Salamone JD (Sep 2008). "Nucleus accumbens adenosine A2A receptors regulate exertion of effort by acting on the ventral striatopallidal pathway". The Journal of Neuroscience 28 (36): 9037–46. doi:10.1523/JNEUROSCI.1525-08.2008. PMC 2806668. PMID 18768698.
  24. ↑ Ongini E, Monopoli A, Cacciari B, Baraldi PG (2001). "Selective adenosine A2A receptor antagonists". Farmaco 56 (1-2): 87–90. doi:10.1016/S0014-827X(01)01024-2. PMID 11347973.
  25. ↑ Baraldi PG, Cacciari B, Romagnoli R, Spalluto G, Monopoli A, Ongini E, Varani K, Borea PA (Jan 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. doi:10.1021/jm010924c. PMID 11754583.
  26. ↑ Baraldi PG, Fruttarolo F, Tabrizi MA, Preti D, Romagnoli R, El-Kashef H, Moorman A, Varani K, Gessi S, Merighi S, Borea PA (Mar 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. doi:10.1021/jm021023m. PMID 12646033.
  27. ↑ Weiss SM, Benwell K, Cliffe IA, Gillespie RJ, Knight AR, Lerpiniere J, Misra A, Pratt RM, Revell D, Upton R, Dourish CT (Dec 2003). "Discovery of nonxanthine adenosine A2A receptor antagonists for the treatment of Parkinson's disease". Neurology 61 (11 Suppl 6): S101–6. doi:10.1212/01.WNL.0000095581.20961.7D. PMID 14663021.
  28. ↑ 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. doi:10.2174/1568026033392282. PMID 12570757.
  29. ↑ Cacciari B, Pastorin G, Spalluto G (2003). "Medicinal chemistry of A2A adenosine receptor antagonists". Current Topics in Medicinal Chemistry 3 (4): 403–11. doi:10.2174/1568026033392183. PMID 12570758.
  30. ↑ Cristalli G, Cacciari B, Dal Ben D, Lambertucci C, Moro S, Spalluto G, Volpini R (Mar 2007). "Highlights on the development of A(2A) adenosine receptor agonists and antagonists". ChemMedChem 2 (3): 260–81. doi:10.1002/cmdc.200600193. PMID 17177231.
  31. ↑ 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. doi:10.2174/138161208784746842. PMID 18673194.
  32. ↑ 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. doi:10.2174/138161208784480081. PMID 18537675.
  33. ↑ 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. doi:10.1016/j.bmcl.2008.03.075. PMID 18406614.
  34. ↑ 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. doi:10.1016/j.bmcl.2008.03.076. PMID 18407496.
  35. ↑ 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. doi:10.1016/j.bmcl.2008.03.072. PMID 18411049.
  36. ↑ Sullivan GW (Nov 2003). "Adenosine A2A receptor agonists as anti-inflammatory agents". Current Opinion in Investigational Drugs (London, England : 2000) 4 (11): 1313–9. PMID 14758770.
  37. ↑ Lappas CM, Sullivan GW, Linden J (Jul 2005). "Adenosine A2A agonists in development for the treatment of inflammation". Expert Opinion on Investigational Drugs 14 (7): 797–806. doi:10.1517/13543784.14.7.797. PMID 16022569.
  38. ↑ El Yacoubi M, Costentin J, Vaugeois JM (Dec 2003). "Adenosine A2A receptors and depression". Neurology 61 (11 Suppl 6): S82–7. doi:10.1212/01.WNL.0000095220.87550.F6. PMID 14663017.
  39. ↑ Kaster MP, Rosa AO, Rosso MM, Goulart EC, Santos AR, Rodrigues AL (Jan 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. doi:10.1016/j.neulet.2003.10.040. PMID 14729225.
  40. ↑ Takahashi RN, Pamplona FA, Prediger RD (2008). "Adenosine receptor antagonists for cognitive dysfunction: a review of animal studies". Frontiers in Bioscience 13 (13): 2614–32. doi:10.2741/2870. PMID 17981738.
  41. ↑ 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. doi:10.1016/j.pnpbp.2008.01.012. PMID 18289757.
  42. ↑ Burton JH, Mass M, Menegazzi JJ, Yealy DM (Aug 1997). "Aminophylline as an adjunct to standard advanced cardiac life support in prolonged cardiac arrest". Annals of Emergency Medicine 30 (2): 154–8. doi:10.1016/S0196-0644(97)70134-3. PMID 9250637.
  43. ↑ Khoury MY, Moukarbel GV, Obeid MY, Alam SE (May 2001). "Effect of aminophylline on complete atrioventricular block with ventricular asystole following blunt chest trauma". Injury 32 (4): 335–8. doi:10.1016/S0020-1383(00)00222-9. PMID 11325371.
  44. ↑ Mader TJ, Bertolet B, Ornato JP, Gutterman JM (Oct 2000). "Aminophylline in the treatment of atropine-resistant bradyasystole". Resuscitation 47 (2): 105–12. doi:10.1016/S0300-9572(00)00234-3. PMID 11008148.
  45. ↑ Mader TJ, Smithline HA, Durkin L, Scriver G (Mar 2003). "A randomized controlled trial of intravenous aminophylline for atropine-resistant out-of-hospital asystolic cardiac arrest". Academic Emergency Medicine 10 (3): 192–7. doi:10.1197/aemj.10.3.192. PMID 12615581.
  46. ↑ Mader TJ, Gibson P (Aug 1997). "Adenosine receptor antagonism in refractory asystolic cardiac arrest: results of a human pilot study". Resuscitation 35 (1): 3–7. doi:10.1016/S0300-9572(97)01097-6. PMID 9259053.
  47. ↑ Perouansky M, Shamir M, Hershkowitz E, Donchin Y (Jul 1998). "Successful resuscitation using aminophylline in refractory cardiac arrest with asystole". Resuscitation 38 (1): 39–41. doi:10.1016/S0300-9572(98)00079-3. PMID 9783508.
  48. ↑ Viskin S, Belhassen B, Roth A, Reicher M, Averbuch M, Sheps D, Shalabye E, Laniado S (Feb 1993). "Aminophylline for bradyasystolic cardiac arrest refractory to atropine and epinephrine". Annals of Internal Medicine 118 (4): 279–81. doi:10.7326/0003-4819-118-4-199302150-00006. PMID 8420445.
  49. ↑ Jenner P (Dec 2003). "A2A antagonists as novel non-dopaminergic therapy for motor dysfunction in PD". Neurology 61 (11 Suppl 6): S32–8. doi:10.1212/01.WNL.0000095209.59347.79. PMID 14663007.
  50. ↑ Mori A, Shindou T (Dec 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. doi:10.1212/01.WNL.0000095211.71092.A0. PMID 14663009.
  51. ↑ Pinna A, Wardas J, Simola N, Morelli M (Nov 2005). "New therapies for the treatment of Parkinson's disease: adenosine A2A receptor antagonists". Life Sciences 77 (26): 3259–67. doi:10.1016/j.lfs.2005.04.029. PMID 15979104.
  52. ↑ Kelsey JE, Langelier NA, Oriel BS, Reedy C (Jan 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. doi:10.1007/s00213-008-1319-0. PMID 18791705.
  53. ↑ Jacobson KA, Gao ZG (Mar 2006). "Adenosine receptors as therapeutic targets". Nature Reviews. Drug Discovery 5 (3): 247–64. doi:10.1038/nrd1983. PMC 3463109. PMID 16518376.
  54. ↑ Yoneyama F, Yamada H, Satoh K, Taira N (Mar 1992). "Vasodepressor mechanisms of 2-(1-octynyl)-adenosine (YT-146), a selective adenosine A2 receptor agonist, involve the opening of glibenclamide-sensitive K+ channels". European Journal of Pharmacology 213 (2): 199–204. doi:10.1016/0014-2999(92)90682-T. PMID 1521559.
  55. ↑ Doyle SE, Breslin FJ, Rieger JM, Beauglehole A, Lynch WJ (Aug 2012). "Time and sex-dependent effects of an adenosine A2A/A1 receptor antagonist on motivation to self-administer cocaine in rats". Pharmacology, Biochemistry, and Behavior 102 (2): 257–263. doi:10.1016/j.pbb.2012.05.001. PMC 3383440. PMID 22579716.
  56. ↑ 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 (Dec 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. doi:10.1212/01.WNL.0000095219.22086.31. PMID 14663020.
  57. ↑ Mott AM, Nunes EJ, Collins LE, Port RG, Sink KS, Hockemeyer J, Müller CE, Salamone JD (May 2009). "The adenosine A2A 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. doi:10.1007/s00213-008-1441-z. PMC 2875244. PMID 19132351.
  58. ↑ 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 (Jul 2009). "Characterization of the potent and highly selective A2A receptor antagonists preladenant and SCH 412348 [7-[2-[4-2,4-difluorophenyl]-1-piperazinyl]ethyl]-2-(2-furanyl)-7H-pyrazolo[4,3-e][1,2,4]triazolo[1,5-c]pyrimidin-5-amine] in rodent models of movement disorders and depression". The Journal of Pharmacology and Experimental Therapeutics 330 (1): 294–303. doi:10.1124/jpet.108.149617. PMID 19332567.
  59. ↑ Pinna A, Fenu S, Morelli M (Mar 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 (New York, N.Y.) 39 (3): 233–8. doi:10.1002/1098-2396(20010301)39:3<233::AID-SYN1004>3.0.CO;2-K. PMID 11284438.
  60. ↑ Rose S, Jackson MJ, Smith LA, Stockwell K, Johnson L, Carminati P, Jenner P (Sep 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. doi:10.1016/j.ejphar.2006.07.017. PMID 16925991.
  61. ↑ Kamiya T, Saitoh O, Yoshioka K, Nakata H (Jun 2003). "Oligomerization of adenosine A2A and dopamine D2 receptors in living cells". Biochemical and Biophysical Research Communications 306 (2): 544–9. doi:10.1016/S0006-291X(03)00991-4. PMID 12804599.

Further reading

  • Ongini E, Adami M, Ferri C, Bertorelli R (Oct 1997). "Adenosine A2A receptors and neuroprotection". Annals of the New York Academy of Sciences 825 (1 Neuroprotecti): 30–48. doi:10.1111/j.1749-6632.1997.tb48412.x. PMID 9369973. 
  • Furlong TJ, Pierce KD, Selbie LA, Shine J (Sep 1992). "Molecular characterization of a human brain adenosine A2 receptor". Brain Research. Molecular Brain Research 15 (1-2): 62–6. doi:10.1016/0169-328X(92)90152-2. PMID 1331670. 
  • Makujina SR, Sabouni MH, Bhatia S, Douglas FL, Mustafa SJ (Oct 1992). "Vasodilatory effects of adenosine A2 receptor agonists CGS 21680 and CGS 22492 in human vasculature". European Journal of Pharmacology 221 (2-3): 243–7. doi:10.1016/0014-2999(92)90708-C. PMID 1426003. 
  • Karlsten R, Gordh T, Post C (Jun 1992). "Local antinociceptive and hyperalgesic effects in the formalin test after peripheral administration of adenosine analogues in mice". Pharmacology & Toxicology 70 (6 Pt 1): 434–8. doi:10.1111/j.1600-0773.1992.tb00503.x. PMID 1438021. 
  • Libert F, Passage E, Parmentier M, Simons MJ, Vassart G, Mattei MG (Sep 1991). "Chromosomal mapping of A1 and A2 adenosine receptors, VIP receptor, and a new subtype of serotonin receptor". Genomics 11 (1): 225–7. doi:10.1016/0888-7543(91)90125-X. PMID 1662665. 
  • 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. doi:10.1016/0306-4522(91)90038-P. PMID 1835521. 
  • 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. doi:10.1126/science.2541503. PMID 2541503. 
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