Advertisement

Adenosine pp 273-306 | Cite as

Adenosine and Stroke

  • Felicita Pedata
  • Anna Maria Pugliese
  • Francesca Corti
  • Alessia Melani
Chapter

Abstract

The concentration of adenosine in the brain increases dramatically during ischemia, and adenosine has long been known to act predominantly as a neuroprotectant during ischemia. In agreement, adenosine infusion into the ischemic striatum significantly ameliorates neurological outcome and reduces the infarct volume after transient focal cerebral ischemia. Despite the neuroprotective effect of adenosine through A1 receptors during ischemia, the use of selective A1 agonists is hampered by unwanted peripheral effects such as sedation, bradycardia, and hypotension. An alternative therapeutic approach may consist of using agents that elevate the local concentration of adenosine at areas of injury-induced adenosine release, thus minimizing undesirable peripheral and central effects mediated by A1 receptors. Adenosine-potentiating agents at injury sites may act by (1) inhibiting its metabolism by adenosine kinase or adenosine deaminase, (2) preventing its transport through equilibrative membrane transporters (ENTs), (3) enhancing hydrolysis of extracellular ATP by use of nucleoside triphosphate diphosphohydrolases (NTPDases) and ecto-5′-nucleotidase (e5′-NTs). The role of A2A receptors also is important for neuroprotection during ischemia. Evidence suggests that low doses of A2A antagonists (that do not modify hemodynamic parameters) provide protection via centrally mediated control of precocious excessive excitotoxicity, while A2A agonists provide protection by controlling massive cell infiltration in the hours after ischemia. Information suggests that A2A receptors are a potentially attractive therapeutic target in ischemia. In perspective of using adenosine A2A active drugs to protect against brain ischemia, attention should be given to the dose and administration time after injury. Although much is still to be learned about the function of the A3 receptor, at the present time it can be speculated that A3 receptor selective ligands may be useful in the treatment of ischemic conditions involving inflammation.

Keywords

Adenosine Adenosine receptors Excitotoxicity Infiltration Neuroprotection Stroke 

References

  1. Abbracchio MP, Cattabeni F (1999) Brain adenosine receptors as targets for therapeutic intervention in neurodegenerative diseases. Ann N Y Acad Sci 890:79–92PubMedCrossRefGoogle Scholar
  2. Abbracchio MP, Ceruti S, Brambilla R, Franceschi C, Malorni W, Jacobson KA, von Lubitz DK, Cattabeni F (1997) Modulation of apoptosis by adenosine in the central nervous system: a possible role for the A3 receptor. Pathophysiological significance and therapeutic implications for neurodegenerative disorders. Ann N Y Acad Sci 825:11–22PubMedCrossRefGoogle Scholar
  3. Adén U, Halldner L, Lagercrantz H, Dalmau I, Ledent C, Fredholm BB (2003) Aggravated brain damage after hypoxic ischemia in immature adenosine A2A knockout mice. Stroke 34:739–744PubMedCrossRefGoogle Scholar
  4. Akopov SE, Simonian NA, Grigorian GS (1996) Dynamics of polymorphonuclear leukocyte accumulation in acute cerebral infarction and their correlation with brain tissue damage. Stroke 27:1739–1743PubMedCrossRefGoogle Scholar
  5. Andiné P (1993) Involvement of adenosine in ischemic and postischemic calcium regulation. Mol Chem Neuropathol 18:35–49PubMedCrossRefGoogle Scholar
  6. Andiné P, Rudolphi KA, Fredholm BB, Hagberg H (1990) Effect of propentofylline (HWA 285) on extracellular purines and excitatory amino acids in CA1 of rat hippocampus during transient ischaemia. Br J Pharmacol 100:814–818PubMedCrossRefGoogle Scholar
  7. Arrigoni E, Crocker AJ, Saper CB, Greene RW, Scammell TE (2005) Deletion of presynaptic adenosine A1 receptors impairs the recovery of synaptic transmission after hypoxia. Neuroscience 132:575–580PubMedCrossRefGoogle Scholar
  8. Attali B, Wang N, Kolot A, Sobko A, Cherepanov V, Soliven B (1997) Characterization of delayed rectifier Kv channels in oligodendrocytes and progenitor cells. J Neurosci 17:8234–8245PubMedGoogle Scholar
  9. Back SA (2006) Perinatal white matter injury: the changing spectrum of pathology and emerging insights into pathogenetic mechanisms. Ment Retard Dev Disabil Res Rev 12:129–140PubMedCrossRefGoogle Scholar
  10. Baines AE, Corrêa SA, Irving AJ, Frenguelli BG (2011) Differential trafficking of adenosine receptors in hippocampal neurons monitored using GFP- and super-ecliptic pHluorin-tagged receptors. Neuropharmacology 61:1–11PubMedCrossRefGoogle Scholar
  11. Baraldi PG, Cacciari B, Romagnoli R, Merighi S, Varani K, Borea PA, Spalluto G (2000) A(3) adenosine receptor ligands: history and perspectives. Med Res Rev 20:103–128PubMedCrossRefGoogle Scholar
  12. Barone FC, Irving EA, Ray AM, Lee JC, Kassis S, Kumar S, Badger AM, Legos JJ, Erhardt JA, Ohlstein EH, Hunter AJ, Harrison DC, Philpott K, Smith BR, Adams JL, Parsons AA (2001) Inhibition of p38 mitogen-activated protein kinase provides neuroprotection in cerebral focal ischemia. Med Res Rev 21:129–145PubMedCrossRefGoogle Scholar
  13. Belayev L, Khoutorova L, Deisher TA, Belayev A, Busto R, Zhang Y, Zhao W, Ginsberg MD (2003) Neuroprotective effect of SolCD39, a novel platelet aggregation inhibitor, on transient middle cerebral artery occlusion in rats. Stroke 34:758–763PubMedCrossRefGoogle Scholar
  14. Bjorklund O, Shang M, Tonazzini I, Dare E, Fredholm BB (2008) Adenosine A1 and A3 receptors protect astrocytes from hypoxic damage. Eur J Pharmacol 596:6–13PubMedCrossRefGoogle Scholar
  15. Boison D (2006) Adenosine kinase, epilepsy and stroke: mechanisms and therapies. Trends Pharmacol Sci 27:652–658PubMedCrossRefGoogle Scholar
  16. Boissard CG, Lindner MD, Gribkoff VK (1992) Hypoxia produces cell death in the rat hippocampus in the presence of an A1 adenosine receptor antagonist: an anatomical and behavioral study. Neuroscience 48:807–812PubMedCrossRefGoogle Scholar
  17. Bona E, Aden U, Gilland E, Fredholm BB, Hagberg H (1997) Neonatal cerebral hypoxia-ischemia: the effect of adenosine receptor antagonists. Neuropharmacology 36:1327–1338PubMedCrossRefGoogle Scholar
  18. Bonetti B, Stegagno C, Cannella B, Rizzato N, Moretto G, Raine CS (1999) Activation of NF-kappaB and c-jun transcription factors in multiple sclerosis lesions. Implications for oligodendrocyte pathology. Am J Pathol 155:1433–1438PubMedCrossRefGoogle Scholar
  19. Borea PA, Gessi S, Bar-Yehuda S, Fishman P (2009) A3 adenosine receptor: pharmacology and role in disease. Handb Exp Pharmacol 193:297–327PubMedCrossRefGoogle Scholar
  20. Borsello T, Clarke PG, Hirt L, Vercelli A, Repici M, Schorderet DF, Bogousslavsky J, Bonny C (2003) A peptide inhibitor of c-Jun N-terminal kinase protects against excitotoxicity and cerebral ischemia. Nat Med 9:1180–1186PubMedCrossRefGoogle Scholar
  21. Braun N, Lenz C, Gillardon F, Zimmermann M, Zimmermann H (1997) Focal cerebral ischemia enhances glial expression of ecto-5′-nucleotidase. Brain Res 766:213–226PubMedCrossRefGoogle Scholar
  22. Braun N, Zhu Y, Kriegistein J, Culmsee C, Zimmermann H (1998) Upregulation of the enzyme chain hydrolyzing extracellular ATP after transient forebrain ischemia in the rat. J Neurosci 18:4891–4900PubMedGoogle Scholar
  23. Brodie C, Blumberg PM, Jacobson KA (1998) Activation of the A2A adenosine receptor inhibits nitric oxide production in glial cells. FEBS Lett 429:139–142PubMedCrossRefGoogle Scholar
  24. Bruce-Keller AJ (1999) Microglial-neuronal interactions in synaptic damage and recovery. J Neurosci Res 58:191–201PubMedCrossRefGoogle Scholar
  25. Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87:659–797PubMedCrossRefGoogle Scholar
  26. Castillo A, Tolón MR, Fernández-Ruiz J, Romero J, Martinez-Orgado J (2010) The neuroprotective effect of cannabidiol in an in vitro model of newborn hypoxic-ischemic brain damage in mice is mediated by CB(2) and adenosine receptors. Neurobiol Dis 37:434–440PubMedCrossRefGoogle Scholar
  27. Chen JF, Huang Z, Ma J, Zhu J, Moratalla R, Standaert D, Moskowitz MA, Fink JS, Schwarzschild, MA (1999) A(2A) adenosine receptor deficiency attenuates brain injury induced by transient focal ischemia in mice. J Neurosci 19:9192–9200PubMedGoogle Scholar
  28. Chen GJ, Harvey BK, Shen H, Chou J, Victor A, Wang Y (2006) Activation of adenosine A3 receptors reduces ischemic brain injury in rodents. J Neurosci Res 84:1848–1855PubMedCrossRefGoogle Scholar
  29. Chitolina Schetinger MR, Bonan CD, Schierholt RC, Webber A, Arteni N, Emanuelli T, Dias RD, Freitas Sarkis JJ, Netto CA (1998) Nucleotide hydrolysis in rats submitted to global cerebral ischemia: a possible link between preconditioning and adenosine production. J Stroke Cerebrovasc Dis 7:281–286PubMedCrossRefGoogle Scholar
  30. Choi DW (1990) Possible mechanisms limiting N-methyl-d-aspartate receptor overactivation and the therapeutic efficacy of N-methyl-d-aspartate antagonists. Stroke 21:III20–III22PubMedGoogle Scholar
  31. Choukèr A, Thiel M, Lukashev D, Ward JM, Kaufmann I, Apasov S, Sitkovsky MV, Ohta A (2008) Critical role of hypoxia and A2A adenosine receptors in liver tissue-protecting physiological anti-inflammatory pathway. Mol Med 14:116–123PubMedCrossRefGoogle Scholar
  32. Coelho JE, Rebola N, Fragata I, Ribeiro JA, de Mendonça A, Cunha RA (2006) Hypoxia-induced desensitization and internalization of adenosine A1 receptors in the rat hippocampus. Neuroscience 138:1195–1203PubMedCrossRefGoogle Scholar
  33. Colotta V, Catarzi D, Varano F, Capelli F, Lenzi O, Filacchioni G, Martini C, Trincavelli L, Ciampi O, Pugliese AM, Pedata F, Schiesaro A, Morizzo E, Moro S (2007) New 2-arylpyrazolo[3,4-c]quinoline derivatives as potent and selective human A3 adenosine receptor antagonists. Synthesis, pharmacological evaluation, and ligand-receptor modeling studies. J Med Chem 50:4061–4074PubMedCrossRefGoogle Scholar
  34. Colotta V, Catarzi D, Varano F, Lenzi O, Filacchioni G, Martini C, Trincavelli L, Ciampi O, Traini C, Pugliese AM, Pedata F, Morizzo E, Moro S (2008) Synthesis, ligand-receptor modeling studies and pharmacological evaluation of novel 4-modified-2-aryl-1,2,4-triazolo[4,3-a]quinoxalin-1-one derivatives as potent and selective human A3 adenosine receptor antagonists. Bioorg Med Chem 16:6086–6102PubMedCrossRefGoogle Scholar
  35. Colotta V, Lenzi O, Catarzi D, Varano F, Filacchioni G, Martini C, Trincavelli L, Ciampi O, Pugliese AM, Traini C, Pedata F, Morizzo E, Moro S (2009) Pyrido[2,3-e]-1,2,4-triazolo[4,3-a]pyrazin-1-one as a new scaffold to develop potent and selective human A3 adenosine receptor antagonists. Synthesis, pharmacological evaluation, and ligand-receptor modeling studies. J Med Chem 52:2407–2419PubMedCrossRefGoogle Scholar
  36. Corradetti R, Lo CG, Moroni F, Passani MB, Pepeu G (1984) Adenosine decreases aspartate and glutamate release from rat hippocampal slices. Eur J Pharmacol 104:19–26PubMedCrossRefGoogle Scholar
  37. Corsi C, Melani A, Bianchi L, Pepeu G, Pedata F (1999) Striatal A2A adenosine receptors differentially regulate spontaneous and K+-evoked glutamate release in vivo in young and aged rats. Neuroreport 10:687–691PubMedCrossRefGoogle Scholar
  38. Corsi C, Melani A, Bianchi L, Pedata F (2000) Striatal A2A adenosine receptor antagonism differentially modifies striatal glutamate outflow in vivo in young and aged rats. Neuroreport 11:2591–2595PubMedCrossRefGoogle Scholar
  39. Cristalli G, Müller CE, Volpini R (2009) Recent developments in adenosine A2A receptor ligands. Handb Exp Pharmacol 193:59–98PubMedCrossRefGoogle Scholar
  40. Cunha RA (2001) Adenosine as a neuromodulator and as a homeostatic regulator in the nervous system: different roles, different sources and different receptors. Neurochem Int 38:107–125PubMedCrossRefGoogle Scholar
  41. Dai SS, Zhou YG, Li W, An JH, Li P, Yang N, Chen XY, Xiong RP, Liu P, Zhao Y, Shen HY, Zhu PF, Chen JF (2010) Local glutamate level dictates adenosine A2A receptor regulation of neuroinflammation and traumatic brain injury. J Neurosci 30:5802–5810PubMedCrossRefGoogle Scholar
  42. Dale N, Pearson T, Fringuelli BG (2000) Direct measurement of adenosine release during hypoxia in the CA1 region of the rat hippocampal slice. J Physiol 526 Pt 1:143–155Google Scholar
  43. Daly JW, Padgett W, Thompson RD, Kusachi S, Bugni WJ, Olsson RA (1986) Structure-activity relationships for N6-substituted adenosines at a brain A1-adenosine receptor with a comparison to an A2-adenosine receptor regulating coronary blood flow. Biochem Pharmacol 35:2467–2481Google Scholar
  44. Daly JW, Padgett WL (1992) Agonist activity of 2- and 5¢-substituted adenosine analogs and their N6-cycloalkyl derivatives at A1- and A2-adenosine receptors coupled to adenylate cyclase. Biochem Pharmacol 43:1089–1093Google Scholar
  45. Daré E, Schulte G, Karovic O, Hammarberg C, Fredholm BB (2007) Modulation of glial cell functions by adenosine receptors. Physiol Behav 92:15–20PubMedCrossRefGoogle Scholar
  46. Daval JL, Nicolas F (1994) Opposite effects of cyclohexyladenosine and theophylline on hypoxic damage in cultured neurons. Neurosci Lett 175:114–116PubMedCrossRefGoogle Scholar
  47. Daval JL, Von Lubitz DK, Deckert J, Redmond DJ, Marangos PJ (1989) Protective effect of cyclohexyladenosine on adenosine A1-receptors, guanine nucleotide and forskolin binding sites following transient brain ischemia: a quantitative autoradiographic study. Brain Res 491:212–226PubMedCrossRefGoogle Scholar
  48. De Keyser J, Sulter G, Luiten PG (1999) Clinical trials with neuroprotective drugs in acute ischaemic stroke: are we doing the right thing? Trends Neurosci 22:535–540PubMedCrossRefGoogle Scholar
  49. DeLeo J, Schubert P, Kreutzberg GW (1988) Protection against ischemic brain damage using propentofylline in gerbils. Stroke 19:1535–1539PubMedCrossRefGoogle Scholar
  50. Di Iorio P, Kleywegt S, Ciccarelli R, Traversa U, Andrew CM, Crocker CE, Werstiuk ES, Rathbone MP (2002) Mechanisms of apoptosis induced by purine nucleosides in astrocytes. Glia 38:179–190PubMedCrossRefGoogle Scholar
  51. Dirnagl U, Iadecola C, Moskowitz MA (1999) Pathobiology of ischaemic stroke: an integrated view. Trends Neurosci 22:391–397PubMedCrossRefGoogle Scholar
  52. Dixon AK, Gubitz AK, Sirinathsinghji DJ, Richardson PJ, Freeman TC (1996) Tissue distribution of adenosine receptor mRNAs in the rat. Br J Pharmacol 118:1461–1468PubMedCrossRefGoogle Scholar
  53. Domenici MR, de Carolis AS, Sagratella S (1996) Block by N6-L-phenylisopropyl-adenosine of the electrophysiological and morphological correlates of hippocampal ischaemic injury in the gerbil. Br J Pharmacol 118:1551–1557PubMedCrossRefGoogle Scholar
  54. Duan W, Gui L, Zhou Z, Liu Y, Tian H, Chen JF, Zheng J (2009) Adenosine A2A receptor deficiency exacerbates white matter lesions and cognitive deficits induced by chronic cerebral hypoperfusion in mice. J Neurol Sci 285:39–45PubMedCrossRefGoogle Scholar
  55. Dunwiddie TV (1984) Interactions between the effects of adenosine and calcium on synaptic responses in rat hippocampus in vitro. J Physiol 350:545–559PubMedGoogle Scholar
  56. Dux E, Fastbom J, Ungerstedt U, Rudolphi K, Fredholm BB (1990) Protective effect of adenosine and a novel xanthine derivative propentofylline on the cell damage after bilateral carotid occlusion in the gerbil hippocampus. Brain Res 516:248–256PubMedCrossRefGoogle Scholar
  57. Ekdahl CT, Claasen JH, Bonde S, Kokaia Z, Lindvall O (2003) Inflammation is detrimental for neurogenesis in adult brain. Proc Natl Acad Sci USA 100:13632–13637PubMedCrossRefGoogle Scholar
  58. Ekdahl CT, Kokaia Z, Lindvall O (2009) Brain inflammation and adult neurogenesis: the dual role of microglia. Neuroscience 158:1021–1029PubMedCrossRefGoogle Scholar
  59. Evans MC, Swan JH, Meldrum BS (1987) An adenosine analogue, 2-chloroadenosine, protects against long term development of ischaemic cell loss in the rat hippocampus. Neurosci Lett 83:287–292PubMedCrossRefGoogle Scholar
  60. Fedorova IM, Jacobson MA, Basile A, Jacobson KA (2003) Behavioral characterization of mice lacking the A3 adenosine receptor: sensitivity to hypoxic neurodegeneration. Cell Mol Neurobiol 23:431–447PubMedCrossRefGoogle Scholar
  61. Fiebich BL, Biber K, Lieb K, van Calker D, Berger M, Bauer J, Gebicke-Haerter PJ (1996) Cyclooxygenase-2 expression in rat microglia is induced by adenosine A2a-receptors. Glia 18:152–160PubMedCrossRefGoogle Scholar
  62. Fishman P, Bar-Yehuda S (2003) Pharmacology and therapeutic applications of A3 receptor subtype. Curr Top Med Chem 3:463–469PubMedCrossRefGoogle Scholar
  63. Fowler JC (1989) Adenosine antagonists delay hypoxia-induced depression of neuronal activity in hippocampal brain slice. Brain Res 490:378–384PubMedCrossRefGoogle Scholar
  64. Fowler JC (1990) Adenosine antagonists alter the synaptic response to in vitro ischemia in the rat hippocampus. Brain Res 509:331–334PubMedCrossRefGoogle Scholar
  65. Fowler JC, Gervitz LM, Hamilton ME, Walker JA (2003) Systemic hypoxia and the depression of synaptic transmission in rat hippocampus after carotid artery occlusion. J Physiol 550:961–972PubMedCrossRefGoogle Scholar
  66. Frassetto SS, Schetinger MR, Schierholt R, Webber A, Bonan CD, Wyse AT, Dias RD, Netto CA, Sarkis JJ (2000) Brain ischemia alters platelet ATP diphosphohydrolase and 5′-nucleotidase activities in naive and preconditioned rats. Braz J Med Biol Res 33:1369–1377PubMedCrossRefGoogle Scholar
  67. Fredholm BB, Jacobson KA, Klotz KN, Linden J (2001) International union of pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol Rev 53:527–552PubMedGoogle Scholar
  68. Fredholm BB, Cunha RA, Svenningsson P (2003) Pharmacology of adenosine A(2A) receptors and therapeutic applications. Curr Top Med Chem 3:413–426PubMedCrossRefGoogle Scholar
  69. Fredholm BB, Chen JF, Masino SA, Vaugeois JM (2005) Actions of adenosine at its receptors in the CNS: insights from knockouts and drugs. Annu Rev Pharmacol Toxicol 45:385–412PubMedCrossRefGoogle Scholar
  70. Fredholm BB, Ijzerman AP, Jacobson KA, Linden J, Müller CE (2011) International Union of Basic and Clinical Pharmacology. LXXXI. Nomenclature and classification of adenosine receptors―an update. Pharmacol Rev 63:1–34PubMedCrossRefGoogle Scholar
  71. Frenguelli BG, Wigmore G, Llaudet E et al (2007) Temporal and mechanistic dissociation of ATP and adenosine release during ischaemia in the mammalian hippocampus. J Neurochem 101:1400–1413PubMedCrossRefGoogle Scholar
  72. Gao Y, Phillis JW (1994) CGS 15943, an adenosine A2 receptor antagonist, reduces cerebral ischemic injury in the Mongolian gerbil. Life Sci 55:61–65CrossRefGoogle Scholar
  73. Gao ZG, Blaustein JB, Gross AS, Melman N, Jacobson KA (2003) N6-Substituted adenosine derivatives: selectivity, efficacy, and species differences at A3 adenosine receptors. Biochem Pharmacol 65(10): 1675–1684Google Scholar
  74. Gáspárová Z, Jariabka P, Stolc S (2008) Effect of the pyridoindole SMe1EC2 and compounds affecting A(1) and A(2A) adenosine receptors in rat hippocampus under ischemia in vitro. Pharmacol Rep 60:353–360PubMedGoogle Scholar
  75. Geiger JD, Nagy JI (1986) Distribution of adenosine deaminase activity in rat brain and spinal cord. J Neurosci 6:2707–2714PubMedGoogle Scholar
  76. Gelderblom M, Eminel S, Herdegen T, Waetzig V (2004) c-Jun N-terminal kinases (JNKs) and the cytoskeleton―functions beyond neurodegeneration. Int J Dev Neurosci 22:559–564PubMedCrossRefGoogle Scholar
  77. Gelderblom M, Leypoldt F, Steinbach K, Behrens D, Choe CU, Siler DA, Arumugam TV, Orthey E, Gerloff C, Tolosa E, Magnus T (2009) Temporal and spatial dynamics of cerebral immune cell accumulation in stroke. Stroke 40:1849–1857PubMedCrossRefGoogle Scholar
  78. Genovese T, Melani A, Esposito E, Paterniti I, Mazzon E, Di Paola R, Bramanti P, Linden J, Pedata F, Cuzzocrea S (2010) Selective adenosine A(2a) receptor agonists reduce the apoptosis in an experimental model of spinal cord trauma. J Biol Regul Homeost Agents 24:73–86PubMedGoogle Scholar
  79. Gervitz LM, Lutherer LO, Davies DG, Pirch JH, Fowler JC (2001) Adenosine induces initial hypoxic-ischemic depression of synaptic transmission in the rat hippocampus in vivo. Am J Physiol Regul Integr Comp Physiol 280:R639–R645PubMedGoogle Scholar
  80. Gervitz LM, Davies DG, Omidvar K, Fowler JC (2003) The effect of acute hypoxemia and hypotension on adenosine-mediated depression of evoked hippocampal synaptic transmission. Exp Neurol 182:507–517PubMedCrossRefGoogle Scholar
  81. Gessi S, Merighi S, Varani K, Leung E, Mac Lennan S, Borea PA (2008) The A3 adenosine receptor: an enigmatic player in cell biology. Pharmacol Ther 117(1):123–140PubMedCrossRefGoogle Scholar
  82. Gidday JM, Fitzgibbons JC, Shah AR, Kraujalis MJ, Park TS (1995) Reduction in cerebral ischemic injury in the newborn rat by potentiation of endogenous adenosine. Pediatr Res 38:306–311PubMedCrossRefGoogle Scholar
  83. Goldberg MP, Monyer H, Weiss JH, Choi DW (1988) Adenosine reduces cortical neuronal injury induced by oxygen or glucose deprivation in vitro. Neurosci Lett 89:323–327PubMedCrossRefGoogle Scholar
  84. Gomes CV, Kaster MP, Tomé AR, Agostinho PM, Cunha RA (2011) Adenosine receptors and brain diseases: neuroprotection and neurodegeneration. Biochim Biophys Acta. 1808(5):1380–1399PubMedCrossRefGoogle Scholar
  85. Gourine AV, Dale N, Gourine VN, Spyer KM (2004) Fever in systemic inflammation: roles of purines. Front Biosci 9:1011–1022PubMedCrossRefGoogle Scholar
  86. Greene RW, Haas HL (1991) The electrophysiology of adenosine in the mammalian central nervous system. Prog Neurobiol 36:329–341PubMedCrossRefGoogle Scholar
  87. Gribkoff VK, Bauman LA, VanderMaelen CP (1990) The adenosine antagonist 8-cyclopentyltheophylline reduces the depression of hippocampal neuronal responses during hypoxia. Brain Res 512:353–357PubMedCrossRefGoogle Scholar
  88. Gui L, Duan W, Tian H, Li C, Zhu J, Chen JF, Zheng J (2009) Adenosine A2A receptor deficiency reduces striatal glutamate outflow and attenuates brain injury induced by transient focal cerebral ischemia in mice. Brain Res 1297:185–193PubMedCrossRefGoogle Scholar
  89. Hagberg H, Andersson P, Lacarewicz J, Jacobson I, Butcher S, Sandberg M (1987) Extracellular adenosine, inosine, hypoxanthine, and xanthine in relation to tissue nucleotides and purines in rat striatum during transient ischemia. J Neurochem 49:227–231PubMedCrossRefGoogle Scholar
  90. Han ME, Park KH, Baek SY, Kim BS, Kim JB, Kim HJ, Oh SO (2007) Inhibitory effects of caffeine on hippocampal neurogenesis and function. Biochem Biophys Res Commun 356:976–980PubMedCrossRefGoogle Scholar
  91. Haskó G, Linden J, Cronstein B, Pacher P (2008) Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov 7:759–770PubMedCrossRefGoogle Scholar
  92. Hentschel S, Lewerenz A, Nieber K (2003) Activation of A(3) receptors by endogenous adenosine inhibits synaptic transmission during hypoxia in rat cortical neurons. Restor Neurol Neurosci 21:55–63PubMedGoogle Scholar
  93. Heron A, Lekieffre D, Le Peillet E, Lasbennes F, Seylaz J, Plotkine M, Boulu RG (1994) Effects of an A1 adenosine receptor agonist on the neurochemical, behavioral and histological consequences of ischemia. Brain Res 641:217–224PubMedCrossRefGoogle Scholar
  94. Hettinger BD, Lee A, Linden J, Rosin DL (2001) Ultrastructural localization of adenosine A2A receptors suggests multiple cellular sites for modulation of GABAergic neurons in rat striatum. J Comp Neurol 431:331–346PubMedCrossRefGoogle Scholar
  95. Heurteaux C, Lauritzen I, Widmann C, Lazdunski M (1995) Essential role of adenosine, adenosine A1 receptors, and ATP-sensitive K+  channels in cerebral ischemic preconditioning. Proc Natl Acad Sci USA 92:4666–4670PubMedCrossRefGoogle Scholar
  96. Higashi H, Meno JR, Marwaha AS, Winn HR (2002) Hippocampal injury and neurobehavioral deficits following hyperglycemic cerebral ischemia: effect of theophylline and ZM 241385. J Neurosurg 96:117–126PubMedCrossRefGoogle Scholar
  97. Hirt L, Badaut J, Thevenet J, Granziera C, Regli L, Maurer F, Bonny C, Bogousslavsky J (2004) D-JNKI1, a cell-penetrating c-Jun-N-terminal kinase inhibitor, protects against cell death in severe cerebral ischemia. Stroke 35:1738–1743PubMedCrossRefGoogle Scholar
  98. Howe CL, Bieber AJ, Warrington AE, Pease LR, Rodriguez M (2004) Antiapoptotic signaling by a remyelination-promoting human antimyelin antibody. Neurobiol Dis 15:120–131PubMedCrossRefGoogle Scholar
  99. Huang J, Upadhyay UM, Tamargo RJ (2006) Inflammation in stroke and focal cerebral ischemia. Surg Neurol 66:232–245PubMedCrossRefGoogle Scholar
  100. Irving EA, Barone FC, Reith AD, Hadingham SJ, Parsons AA (2000) Differential activation of MAPK/ERK and p38/SAPK in neurones and glia following focal cerebral ischaemia in the rat. Brain Res Mol Brain Res 77:65–75PubMedCrossRefGoogle Scholar
  101. Jacobson KA (1998) Adenosine A3 receptors: novel ligands and paradoxical effects. Trends Pharmacol Sci 19:184–191PubMedCrossRefGoogle Scholar
  102. Jacobson KA, Gao ZG (2006) Adenosine receptors as therapeutic targets. Nature Rev 5:247–264CrossRefGoogle Scholar
  103. Jacobson KA, Nikodijević O, Shi D, Gallo-Rodriguez C, Olah ME, Stiles GL, Daly JW (1993) A role for central A3-adenosine receptors. Mediation of behavioral depressant effects. FEBS Lett 336:57–60PubMedCrossRefGoogle Scholar
  104. Jacobson KA, Von Lubitz DK, Daly JW, Fredholm BB (1996) Adenosine receptor ligands: differences with acute versus chronic treatment. Trends Pharmacol Sci 17:108–113PubMedCrossRefGoogle Scholar
  105. Jacobson KA, Hoffmann C, Cattabeni F, Abbracchio MP (1999) Adenosine-induced cell death: evidence for receptor-mediated signalling. Apoptosis 4:197–211PubMedCrossRefGoogle Scholar
  106. Jarrott DM, Domer FR (1980) A gerbil model of cerebral ischemia suitable for drug evaluation. Stroke 11:203–209PubMedCrossRefGoogle Scholar
  107. Jiang N, Kowaluk EA, Lee CH, Mazdiyasni H, Chopp M (1997) Adenosine kinase inhibition protects brain against transient focal ischemia in rats. Eur J Pharmacol 320:131–137PubMedCrossRefGoogle Scholar
  108. Johansson B, Halldner L, Dunwiddie TV, Masino SA, Poelchen W, Giménez-Llort L, Escorihuela RM, Fernández-Teruel A, Wiesenfeld-Hallin Z, Xu XJ, Hårdemark A, Betsholtz C, Herlenius E, Fredholm BB (2001) Hyperalgesia, anxiety, and decreased hypoxic neuroprotection in mice lacking the adenosine A1 receptor. Proc Natl Acad Sci USA 98:9407–9412PubMedCrossRefGoogle Scholar
  109. Johnson MP, McCarty DR, Chmielewski PA (1998) Temporal dependent neuroprotection with propentofylline (HWA 285) in a temporary focal ischemia model. Eur J Pharmacol 346:151–157PubMedCrossRefGoogle Scholar
  110. Jones PA, Smith RA, Stone TW (1998a) Protection against kainate-induced excitotoxicity by adenosine A2A receptor agonists and antagonists. Neuroscience 85:229–237PubMedCrossRefGoogle Scholar
  111. Jones PA, Smith RA, Stone TW (1998b) Protection against hippocampal kainate excitotoxicity by intracerebral administration of an adenosine A2A receptor antagonist. Brain Res 800:328–335PubMedCrossRefGoogle Scholar
  112. Jurewicz A, Matysiak M, Andrzejak S, Selmaj K (2006) TRAIL-induced death of human adult oligodendrocytes is mediated by JNK pathway. Glia 53:158–166PubMedCrossRefGoogle Scholar
  113. Kano T, Katayama Y, Kawamata T, Hirota H, Tsubokawa T (1994) Propentofylline administered by microdialysis attenuates ischemia-induced hippocampal damage but not excitatory amino acid release in gerbils. Brain Res 641:149–154PubMedCrossRefGoogle Scholar
  114. Kawahara N, Ide T, Saito N, Kawai K, Kirino T (1998) Propentofylline potentiates induced ischemic tolerance in gerbil hippocampal neurons via adenosine receptor. J Cereb Blood Flow Metab 18:472–475PubMedCrossRefGoogle Scholar
  115. Kawasaki H, Morooka T, Shimohama S, Kimura J, Hirano T, Gotoh Y, Nishida E (1997) Activation and involvement of p38 mitogen-activated protein kinase in glutamate-induced apoptosis in rat cerebellar granule cells. J Biol Chem 272:18518–18521PubMedCrossRefGoogle Scholar
  116. King AE, Ackley MA, Cass CE et al (2006) Nucleoside transporters: from scavengers to novel therapeutic targets. Trends Pharmacol Sci 27:416–425PubMedCrossRefGoogle Scholar
  117. Kitada M, Rowitch DH (2006) Transcription factor co-expression patterns indicate heterogeneity of oligodendroglial subpopulations in adult spinal cord. Glia 54:35–46PubMedCrossRefGoogle Scholar
  118. Kitagawa H, Mori A, Shimada J, Mitsumoto Y, Kikuchi T (2002) Intracerebral adenosine infusion improves neurological outcome after transient focal ischemia in rats. Neurol Res 24:317–323PubMedCrossRefGoogle Scholar
  119. Kobayashi T, Yamada T, Okada Y (1998) The levels of adenosine and its metabolites in the guinea pig and rat brain during complete ischemia-in vivo study. Brain Res 787:211–219PubMedCrossRefGoogle Scholar
  120. Kuan CY, Whitmarsh AJ, Yang DD, Liao G, Schloemer AJ, Dong C, Bao J, Banasiak KJ, Haddad GG, Flavell RA, Davis RJ, Rakic P (2003) A critical role of neural-specific JNK3 for ischemic apoptosis. Proc Natl Acad Sci USA 100:15184–15189PubMedCrossRefGoogle Scholar
  121. Kuroiwa T, Ting P, Martinez H, Klatzo I (1985) The biphasic opening of the blood-brain barrier to proteins following temporary middle cerebral artery occlusion. Acta Neuropathol 68:122–129PubMedCrossRefGoogle Scholar
  122. Kusano Y, Echeverry G, Miekisiak G, Kulik TB, Aronhime SN, Chen JF, Winn HR (2010) Role of adenosine A2 receptors in regulation of cerebral blood flow during induced hypotension. J Cereb Blood Flow Metab 30:808–815PubMedCrossRefGoogle Scholar
  123. Lai D-M, Tu Y-K, Liu I-M, Cheng J-T (2005) Increase of adenosine A1 receptor gene expression in cerebral ischemia of Wistar rats. Neurosci Lett 387:59–61PubMedCrossRefGoogle Scholar
  124. Lange-Asschenfeldt C, Raval AP, Dave KR, Mochly-Rosen D, Sick TJ, Perez-Pinzon MA (2004) Epsilon protein kinase C mediated ischemic tolerance requires activation of the extracellular regulated kinase pathway in the organotypic hippocampal slice. J Cereb Blood Flow Metab 24:636–645PubMedCrossRefGoogle Scholar
  125. Langer D, Ikehara Y, Takebayashi H, Hawkes R, Zimmermann H (2007) The ectonucleotidases alkaline phosphatase and nucleoside triphosphate diphosphohydrolase 2 are associated with subsets of progenitor cell populations in the mouse embryonic, postnatal and adult neurogenic zones. Neuroscience 150:863–879PubMedCrossRefGoogle Scholar
  126. Lappas CM, Day YJ, Marshall MA, Engelhard VH, Linden J (2006) Adenosine A2A receptor activation reduces hepatic ischemia reperfusion injury by inhibiting CD1d-dependent NKT cell activation. J Exp Med 203:2639–2648PubMedCrossRefGoogle Scholar
  127. Latini S, Pedata F (2001) Adenosine in the central nervous system: release mechanisms and extracellular concentrations. J Neurochem 79:463–484PubMedCrossRefGoogle Scholar
  128. Latini S, Corsi C, Pedata F et al (1995) The source of brain adenosine outflow during ischemia and electrical stimulation. Neurochem Int 27:239–244PubMedCrossRefGoogle Scholar
  129. Latini S, Bordoni F, Corradetti R, Pepeu G, Pedata F (1998) Temporal correlation between adenosine outflow and synaptic potential inhibition in rat hippocampal slices during ischemia-like conditions. Brain Res 794:325–328PubMedCrossRefGoogle Scholar
  130. Latini S, Bordoni F, Pedata F, Corradetti R (1999a) Extracellular adenosine concentrations during in vitro ischaemia in rat hippocampal slices. Br J Pharmacol 127:729–739PubMedCrossRefGoogle Scholar
  131. Latini S, Bordoni F, Corradetti R, Pepeu G, Pedata F (1999b) Effect of A2A adenosine receptor stimulation and antagonism on synaptic depression induced by in vitro ischaemia in rat hippocampal slices. Br J Pharmacol 128:1035–1044PubMedCrossRefGoogle Scholar
  132. Lee KS, Lowenkopf T (1993) Endogenous adenosine delays the onset of hypoxic depolarization in the rat hippocampus in vitro via an action at A1 receptors. Brain Res 609:313–315PubMedCrossRefGoogle Scholar
  133. Lewis AJ, Manning AM (1999) New targets for anti-inflammatory drugs. Curr Opin Chem Biol 3:489–494PubMedCrossRefGoogle Scholar
  134. Li Y, Oskouian RJ, Day YJ, Rieger JM, Liu L, Kern JA, Linden J (2006) Mouse spinal cord compression injury is reduced by either activation of the adenosine A2A receptor on bone marrow-derived cells or deletion of the A2A receptor on non-bone marrow-derived cells. Neuroscience 141:2029–2039PubMedCrossRefGoogle Scholar
  135. Liang R, Pang ZP, Deng P, Xu ZC (2009) Transient enhancement of inhibitory synaptic transmission in hippocampal CA1 pyramidal neurons after cerebral ischemia. Neuroscience 160:412–418PubMedCrossRefGoogle Scholar
  136. Lie AA, Blümcke I, Beck H, Wiestler OD, Elger CE, Schoen SW (1999) 5′-Nucleotidase activity indicates sites of synaptic plasticity and reactive synaptogenesis in the human brain. J Neuropathol Exp Neurol 58:451–458PubMedCrossRefGoogle Scholar
  137. Lin Y, Phillis JW (1992) Deoxycoformycin and oxypurinol: protection against focal ischemic brain injury in the rat. Brain Res 571:272–280PubMedCrossRefGoogle Scholar
  138. Lloyd HG, Fredholm BB (1995) Involvement of adenosine deaminase and adenosine kinase in regulating extracellular adenosine concentration in rat hippocampal slices. Neurochem Int 26:387–395PubMedCrossRefGoogle Scholar
  139. Logan M, Sweeney MI (1997) Adenosine A1 receptor activation preferentially protects cultured cerebellar neurons versus astrocytes against hypoxia-induced death. Mol Chem Neuropathol 31:119–133PubMedCrossRefGoogle Scholar
  140. Luo C, Yi B, Tao G, Li M, Chen Z, Tang W, Zhang JH, Feng H (2010) Adenosine A3 receptor agonist reduces early brain injury in subarachnoid haemorrhage. Neuroreport 21:892–896PubMedCrossRefGoogle Scholar
  141. Macek TA, Schaffhauser H, Conn PJ (1998) Protein kinase C and A3 adenosine receptor activation inhibit presynaptic metabotropic glutamate receptor (mGluR) function and uncouple mGluRs from GTP-binding proteins. J Neurosci 18:6138–6146PubMedGoogle Scholar
  142. Madrigal JL, Caso JR, de Cristóbal J et al (2003) Effect of subacute and chronic immobilisation stress on the outcome of permanent focal cerebral ischaemia in rats. Brain Res 979:137–145PubMedCrossRefGoogle Scholar
  143. Marcoli M, Raiteri L, Bonfanti A, Monopoli A, Ongini E, Raiteri M, Maura G (2003) Sensitivity to selective adenosine A1 and A2A receptor antagonists of the release of glutamate induced by ischemia in rat cerebrocortical slices. Neuropharmacology 45:201–210PubMedCrossRefGoogle Scholar
  144. Marcoli M, Bonfanti A, Roccatagliata P, Chiaramonte G, Ongini E, Raiteri M, Maura G (2004) Glutamate efflux from human cerebrocortical slices during ischemia: vesicular-like mode of glutamate release and sensitivity to A(2A) adenosine receptor blockade. Neuropharmacology 47:884–891PubMedCrossRefGoogle Scholar
  145. Marcus AJ, Broekman MJ, Drosopoulos JH, Islam N, Pinsky DJ, Sesti C, Levi R (2003) Metabolic control of excessive extracellular nucleotide accumulation by CD39/ecto-nucleotidase-1: implications for ischemic vascular diseases. J Pharmacol Exp Ther 305:9–16PubMedCrossRefGoogle Scholar
  146. Marks L, Carswell HV, Peters EE, Graham DI, Patterson J, Dominiczak AF, Macrae IM (2001) Characterization of the microglial response to cerebral ischemia in the stroke-prone spontaneously hypertensive rat. Hypertension 38:116–122PubMedCrossRefGoogle Scholar
  147. Matsumoto K, Graf R, Rosner G, Shimada N, Heiss WD (1992) Flow thresholds for extracellular purine catabolite elevation in cat focal ischemia. Brain Res 579:309–314PubMedCrossRefGoogle Scholar
  148. Matsumoto K, Sakaki T, Kohmura E, Hayakawa T, Yamada K (1996) Amelioration of ischemic brain damage by the preischemic administration of propentofylline (HWA285) in a rat focal ischemia. Brain Res 723:228–230PubMedCrossRefGoogle Scholar
  149. Matute C, Sanchez-Gomez MV, Martinez-Millan L, Miledi R (1997) Glutamate receptor-mediated toxicity in optic nerve oligodendrocytes. Proc Natl Acad Sci USA 94:8830–8835PubMedCrossRefGoogle Scholar
  150. Matute C, Alberdi E, Ibarretxe G, Sanchez-Gomez MV (2002) Excitotoxicity in glial cells. Eur J Pharmacol 447:239–246PubMedCrossRefGoogle Scholar
  151. McDonald JW, Althomsons SP, Hyrc KL, Choi DW, Goldberg MP (1998) Oligodendrocytes from forebrain are highly vulnerable to AMPA/kainate receptor-mediated excitotoxicity. Nat Med 4:291–297PubMedCrossRefGoogle Scholar
  152. Melani A, Pantoni L, Corsi C, Bianchi L, Monopoli A, Bertorelli R, Pepeu G, Pedata F (1999) Striatal outflow of adenosine, excitatory amino acids, γ-aminobutyric acid, and taurine in awake freely moving rats after middle cerebral artery occlusion. Correlations with neurological deficit and histopatological damage. Stroke 30:2448–2455PubMedCrossRefGoogle Scholar
  153. Melani A, Pantoni L, Bordoni F, Gianfriddo M, Bianchi L, Vannucchi MG, Bertorelli R, Monopoli A, Pedata F (2003) The selective A2A receptor antagonist SCH 58261 reduces striatal transmitter outflow, turning behavior and ischemic brain damage induced by permanent focal ischemia in the rat. Brain Res 959:243–250PubMedCrossRefGoogle Scholar
  154. Melani A, Amadio S, Gianfriddo M, Vannucchi MG, Volontè C, Bernardi G, Pedata F (2006a) Sancesario G. P2X7 receptor modulation on microglial cells and reduction of brain infarct caused by middle cerebral artery occlusion in rat. J Cereb Blood Flow Metab 26:974–982PubMedCrossRefGoogle Scholar
  155. Melani A, Gianfriddo M, Vannucchi MG, Cipriani S, Baraldi PG, Giovannini MG, Pedata F (2006b) The selective A(2A) receptor antagonist SCH 58261 protects from neurological deficit, brain damage and activation of p38 MAPK in rat focal cerebral ischemia. Brain Res 1073–1074:470–480PubMedCrossRefGoogle Scholar
  156. Melani A, Cipriani S, Vannucchi MG, Nosi D, Donati C, Bruni P, Giovannini MG, Pedata F (2009) Selective adenosine A2A receptor antagonism reduces JNK activation in oligodendrocytes after cerebral ischaemia. Brain 132:1480–1495PubMedCrossRefGoogle Scholar
  157. Melani A, Cipriani S, Corti F, Pedata F (2010) Effect of intravenous administration of dipyridamole in a rat model of chronic cerebral ischemia. Ann N Y Acad Sci 1207:89–96PubMedCrossRefGoogle Scholar
  158. Melani A, Corti F, Vannucchi MG, Nosi D, Giovannini MG, Pedata F (2011) Role of adenosine A2A receptors on modulation of oligodendroglia in cerebral ischemia. Shock 36(Suppl 2):24–25Google Scholar
  159. Melani A, Corti F, Stephan H, Müller CE, Donati C, Bruni P, Vannucchi MG, Pedata F (2012) Ecto-ATPase inhibition: ATP and adenosine release under physiological and ischemic in vivo conditions in the rat striatum. Exp Neurol 233:193–204PubMedCrossRefGoogle Scholar
  160. Migita H, Kominami K, Higashida M, Maruyama R, Tuchida N, McDonald F, Shimada F, Sakurada K (2008) Activation of adenosine A1 receptor-induced neural stem cell proliferation via MEK/ERK and Akt signaling pathways. J Neurosci Res 86:2820–2828PubMedCrossRefGoogle Scholar
  161. Miller LP, Jelovich LA, Yao L, DaRe J, Ugarkar B, Foster AC (1996) Pre- and peristroke treatment with the adenosine kinase inhibitor, 5′-deoxyiodotubercidin, significantly reduces infarct volume after temporary occlusion of the middle cerebral artery in rats. Neurosci Lett 220:73–76PubMedCrossRefGoogle Scholar
  162. Milton SL, Nayak G, Kesaraju S, Kara L, Prentice HM (2007) Suppression of reactive oxygen species production enhances neuronal survival in vitro and in vivo in the anoxia-tolerant turtle Trachemys scripta. J Neurochem 101:993–1001PubMedCrossRefGoogle Scholar
  163. Mirabet M, Herrera C, Cordero OJ, Mallol J, Lluis C, Franco R (1999) Expression of A2B adenosine receptors in human lymphocytes: their role in T cell activation. J Cell Sci 112:491–502PubMedGoogle Scholar
  164. Monopoli A, Lozza G, Forlani A, Mattavelli A, Ongini E (1998) Blockade of A2A adenosine receptors by SCH 58261 results in neuroprotective effects in cerebral ischaemia in rats. Neuroreport 9:3955–3959PubMedCrossRefGoogle Scholar
  165. Mori M, Nishizaki T, Okada Y (1992) Protective effect of adenosine on the anoxic damage of hippocampal slice. Neuroscience 46:301–307PubMedCrossRefGoogle Scholar
  166. Moro S, Gao ZG, Jacobson KA, Spalluto G (2006) Progress in the pursuit of therapeutic adenosine receptor antagonists. Med Res Rev 26: 131–159Google Scholar
  167. Müller CE, Jacobson KA (2011) Recent developments in adenosine receptor ligands and their potential as novel drugs. Biochim Biophys Acta 1808:1290–1308PubMedCrossRefGoogle Scholar
  168. Naganuma M, Wiznerowicz EB, Lappas CM, Linden J, Worthington MT, Ernst PB (2006) Cutting edge: critical role for A2A adenosine receptors in the T cell-mediated regulation of colitis. J Immunol 177:2765–2769PubMedGoogle Scholar
  169. Nagasawa H, Araki T, Kogure K (1994) Alteration of adenosine A1 receptor binding in the post-ischaemic rat brain. Neuroreport 5:1453–1456PubMedCrossRefGoogle Scholar
  170. Nakamura M, Nakakimura K, Matsumoto M, Sakabe T (2002) Rapid tolerance to focal cerebral ischemia in rats is attenuated by adenosine A1 receptor antagonist. J Cereb Blood Flow Metab 22:161–170PubMedCrossRefGoogle Scholar
  171. Newman GC, Hospod FE, Trowbridge SD, Motwani S, Liu Y (1998) Restoring adenine nucleotides in a brain slice model of cerebral reperfusion. J Cereb Blood Flow Metab 18:675–685PubMedCrossRefGoogle Scholar
  172. Nieber K, Hentschel S (2006) Signalling pathways of the adenosine A3 receptors in rat cortical neurons. In: Proceedings of the 8th international symposium on adenosine and adenine nucleotides, Ferrara, Italy, May 24–28Google Scholar
  173. Nishizaki T, Nagai K, Nomura T, Tada H, Kanno T, Tozaki H, Li XX, Kondoh T, Kodama N, Takahashi E, Sakai N, Tanaka K, Saito N (2002) A new neuromodulatory pathway with a glial contribution mediated via A2A adenosine receptors. Glia 39:133–147PubMedCrossRefGoogle Scholar
  174. Odashima M, Bamias G, Rivera-Nieves J, Linden J, Nast CC, Moskaluk CA, Marini M, Sugawara K, Kozaiwa K, Otaka M, Watanabe S, Cominelli F (2005) Activation of A2A adenosine receptor attenuates intestinal inflammation in animal models of inflammatory bowel disease. Gastroenterology 129:26–33PubMedCrossRefGoogle Scholar
  175. Olsson T, Cronberg T, Rytter A, Asztély F, Fredholm BB, Smith ML, Wieloch T (2004) Deletion of the adenosine A1 receptor gene does not alter neuronal damage following ischaemia in vivo or in vitro. Eur J Neurosci 20:1197–1204PubMedCrossRefGoogle Scholar
  176. Ongini E, Adami M, Ferri C, Bertorelli R (1997) Adenosine A2A receptors and neuroprotection. Ann N Y Acad Sci 825:30–48PubMedCrossRefGoogle Scholar
  177. Onodera H, Sato G, Kogure K (1987) Quantitative autoradiographic analysis of muscarinic cholinergic and adenosine A1 binding sites after transient forebrain ischemia in the gerbil. Brain Res 415:309–322PubMedCrossRefGoogle Scholar
  178. O’Regan MH, Simpson RE, Perkins LM, Phillis JW (1992) The selective A2 adenosine receptor agonist CGS 21680 enhances excitatory transmitter amino acid release from the ischemic rat cerebral cortex. Neurosci Lett 138:169–172PubMedCrossRefGoogle Scholar
  179. Palmer TM, Benovic JL, Stiles GL (1995) Agonist-dependent phosphorylation and desensitization of the rat A3 adenosine receptor. Evidence for a G-protein-coupled receptor kinase-mediated mechanism. J Biol Chem 270:29607–29613PubMedCrossRefGoogle Scholar
  180. Park CK, Rudolphi KA (1994) Antiischemic effects of propentofylline (HWA 285) against focal cerebral infarction in rats. Neurosci Lett 178:235–238PubMedCrossRefGoogle Scholar
  181. Parkinson FE, Xiong W, Zamzow CR (2005) Astrocytes and neurons: different roles in regulating adenosine levels. Neurol Res 27:153–160PubMedCrossRefGoogle Scholar
  182. Parkinson FE, Damaraju VL, Graham K, Yao SY, Baldwin SA, Cass CE, Young JD (2011) Molecular biology of nucleoside transporters and their distributions and functions in the brain. Curr Top Med Chem 11:948–972PubMedCrossRefGoogle Scholar
  183. Patel BT, Tudball N (1986) Localization of S-adenosylhomocysteine hydrolase and adenosine deaminase immunoreactivities in rat brain. Brain Res 370:250–264PubMedCrossRefGoogle Scholar
  184. Paterniti I, Melani A, Cipriani S, Corti F, Mello T, Mazzon E, Esposito E, Bramanti P, Cuzzocrea S, Pedata F (2011) Selective adenosine A2A receptor agonists and antagonists protect against spinal cord injury through peripheral and central effects. J Neuroinflammation 8:31PubMedCrossRefGoogle Scholar
  185. Pearson T, Damian K, Lynas RE, Frenguelli BG (2006) Sustained elevation of extracellular adenosine and activation of A1 receptors underlie the post-ischaemic inhibition of neuronal function in rat hippocampus in vitro. J Neurochem 97:1357–1368PubMedCrossRefGoogle Scholar
  186. Pedata F, Latini S, Pugliese AM, Pepeu G (1993) Investigations into the adenosine outflow from hippocampal slices evoked by ischemia-like conditions. J Neurochem 61:284–289PubMedCrossRefGoogle Scholar
  187. Pedata F, Corsi C, Melani A, Bordoni F, Latini S (2001) Adenosine extracellular brain concentrations and role of A2A receptors in ischemia. Ann N Y Acad Sci 939:74–84PubMedCrossRefGoogle Scholar
  188. Pedata F, Pugliese AM, Melani A, Gianfriddo M (2003) A2A receptors in neuroprotection of dopaminergic neurons. Neurology 61:S49–S50PubMedCrossRefGoogle Scholar
  189. Pedata F, Gianfriddo M, Turchi D, Melani A (2005) The protective effect of adenosine A2A receptor antagonism in cerebral ischemia. Neurol Res 27:169–174PubMedCrossRefGoogle Scholar
  190. Pedata F, Pugliese AM, Coppi E, Popoli P, Morelli M, Schwarzschild MA, Melani A (2007) Adenosine in the central nervous system: effects on neurotransmission and neuroprotection. Immunol Endocr Metab Agents Med Chem 4:304–321CrossRefGoogle Scholar
  191. Pedata F, Pugliese AM, Sebastiao AM, Ribeiro JA (2010) Adenosine A3 receptor signaling in the central nervous system. In: Borea PA (ed) A3 adenosine receptor. Springer Science+Business Media B.V. 2010, pp 165–188Google Scholar
  192. Perez-Pinzon MA, Mumford PL, Rosenthal M, Sick TJ (1996) Anoxic preconditioning in hippocampal slices: role of adenosine. Neuroscience 75:687–694PubMedCrossRefGoogle Scholar
  193. Peterfreund RA, MacCollin M, Gusella J, Fink JS (1996) Characterization and expression of the human A2a adenosine receptor gene. J Neurochem 66:362–368PubMedCrossRefGoogle Scholar
  194. Petroni A, Papini N, Blasevich M, Galli C (2002) Blockade of A(2A) adenosine receptors leads to c-fos inhibition in a rat model of brain ischemia. Pharmacol Res 45:125–128PubMedCrossRefGoogle Scholar
  195. Phillis JW (1995) The effects of selective A1 and A2a adenosine receptor antagonists on cerebral ischemic injury in the gerbil. Brain Res 705:79–84PubMedCrossRefGoogle Scholar
  196. Phillis JW (2004) Adenosine and adenine nucleotides as regulators of cerebral blood flow: roles of acidosis, cell swelling, and KATP channels. Crit Rev Neurobiol 16:237–270PubMedCrossRefGoogle Scholar
  197. Phillis JW, Goshgarian HG (2001) Adenosine and neurotrauma: therapeutic perspectives. Neurol Res 23:183–189PubMedCrossRefGoogle Scholar
  198. Phillis JW, O’Regan MH (1989) Deoxycoformycin antagonizes ischemia-induced neuronal degeneration. Brain Res Bull 22:537–540PubMedCrossRefGoogle Scholar
  199. Phillis JW, Edstrom JP, Kostopoulos GK, Kirkpatrick JR (1979) Effects of adenosine and adenine nucleotides on synaptic transmission in the cerebral cortex. Can J Physiol Pharmacol 57:1289–1312PubMedCrossRefGoogle Scholar
  200. Phillis JW, Walter GA, Simpson RE (1991) Brain adenosine and transmitter amino acid release from the ischemic rat cerebral cortex: effects of the adenosine deaminase inhibitor deoxycoformycin. J Neurochem 56:644–650PubMedCrossRefGoogle Scholar
  201. Phillis JW, Smith-Barbour M, O’Regan MH, Perkins LM (1994a) Amino acid and purine release in rat brain following temporary middle cerebral artery occlusion. Neurochem Res 19:1125–1130PubMedCrossRefGoogle Scholar
  202. Phillis JW, Smith-Barbour M, Perkins LM, O’Regan MH (1994b) Indomethacin modulates ischemia-evoked release of glutamate and adenosine from the rat cerebral cortex. Brain Res 652:353–356PubMedCrossRefGoogle Scholar
  203. Phillis JW, Smith-Barbour M, O’Regan MH (1996) Changes in extracellular amino acid neurotransmitters and purines during and following ischemias of different durations in the rat cerebral cortex. Neurochem Int 29:115–120PubMedCrossRefGoogle Scholar
  204. Piao CS, Kim JB, Han PL, Lee JK (2003) Administration of the p38 MAPK inhibitor SB203580 affords brain protection with a wide therapeutic window against focal ischemic insult. J Neurosci Res 73:537–544PubMedCrossRefGoogle Scholar
  205. Pignataro G, Maysami S, Studer FE, Wilz A, Simon RP, Boison D (2008) Downregulation of hippocampal adenosine kinase after focal ischemia as potential endogenous neuroprotective mechanism. J Cereb Blood Flow Metab 28:17–23PubMedCrossRefGoogle Scholar
  206. Pinsky DJ, Broekman MJ, Peschon JJ, Stocking KL, Fujita T, Ramasamy R, Connolly ES Jr, Huang J, Kiss S, Zhang Y, Choudhri TF, McTaggart RA, Liao H, Drosopoulos JH, Price VL, Marcus AJ, Maliszewski CR (2002) Elucidation of the thromboregulatory role of CD39/ectoapyrase in the ischemic brain. J Clin Invest 109:1031–1040PubMedGoogle Scholar
  207. Pintor A, Galluzzo M, Grieco R, Pezzola A, Reggio R, Popoli P (2004) Adenosine A2A receptor antagonists prevent the increase in striatal glutamate levels induced by glutamate uptake inhibitors. J Neurochem 89:152–156PubMedCrossRefGoogle Scholar
  208. Popoli P, Betto P, Reggio R, Ricciarello G (1995) Adenosine A2A receptor stimulation enhances striatal extracellular glutamate levels in rats. Eur J Pharmacol 287:215–217PubMedCrossRefGoogle Scholar
  209. Popoli P, Pintor A, Domenici MR, Frank C, Tebano MT, Pezzola A, Scarchilli L, Quarta D, Reggio R, Malchiodi-Albedi F, Falchi M, Massotti M (2002) Blockade of striatal adenosine A2A receptor reduces, through a presynaptic mechanism, quinolinic acid-induced excitotoxicity: possible relevance to neuroprotective interventions in neurodegenerative diseases of the striatum. J Neurosci 22:1967–1975PubMedGoogle Scholar
  210. Pugliese AM, Latini S, Corradetti R, Pedata F (2003) Brief, repeated, oxygen-glucose deprivation episodes protect neurotransmission from a longer ischemic episode in the in vitro hippocampus: role of adenosine receptors. Br J Pharmacol 140:305–314PubMedCrossRefGoogle Scholar
  211. Pugliese AM, Coppi E, Spalluto G, Corradetti R, Pedata F (2006) A3 adenosine receptor antagonists delay irreversible synaptic failure caused by oxygen and glucose deprivation in the rat CA1 hippocampus in vitro. Br J Pharmacol 147:524–532PubMedCrossRefGoogle Scholar
  212. Pugliese AM, Coppi E, Volpini R, Cristalli G, Corradetti R, Jeong LS, Jacobson KA, Pedata F (2007a) Role of adenosine A3 receptors on CA1 hippocampal neurotransmission during oxygen-glucose deprivation episodes of different duration. Biochem Pharmacol 74:768–779PubMedCrossRefGoogle Scholar
  213. Pugliese AM, Coppi E, Volpini R, Cristalli G, Corradetti R, Jeong LS, Jacobson KA, Pedata F (2007b) Role of adenosine A3 receptors on CA1 hippocampal neurotransmission during oxygen-glucose deprivation episodes of different duration. Biochem Pharmacol 74(5): 768–779Google Scholar
  214. Pugliese AM, Traini C, Cipriani S, Gianfriddo M, Mello T, Giovannini MG, Galli A, Pedata F (2009) The adenosine A2A receptor antagonist ZM241385 enhances neuronal survival after oxygen-glucose deprivation in rat CA1 hippocampal slices. Br J Pharmacol 157:818–830PubMedCrossRefGoogle Scholar
  215. Ribeiro JA, Sebastiao AM, de Mendonca A (2002) Adenosine receptors in the nervous system: pathophysiological implications. Prog Neurobiol 68:377–392PubMedCrossRefGoogle Scholar
  216. Rivkees SA, Zhao Z, Porter G, Turner C (2001) Influences of adenosine on the fetus and newborn. Mol Genet Metab 74:160–171PubMedCrossRefGoogle Scholar
  217. Rosin DL, Hettinger BD, Lee A, Linden J (2003) Anatomy of adenosine A2A receptors in brain: morphological substrates for integration of striatal function. Neurology 61:S10–S11CrossRefGoogle Scholar
  218. Rudolphi KA, Keil M, Hinze HJ (1987) Effect of theophylline on ischemically induced hippocampal damage in Mongolian gerbils: a behavioral and histopathological study. J Cereb Blood Flow Metab 7:74–81PubMedCrossRefGoogle Scholar
  219. Rudolphi KA, Keil M, Fastbom J, Fredholm BB (1989) Ischaemic damage in gerbil hippocampus is reduced following upregulation of adenosine (A1) receptors by caffeine treatment. Neurosci Lett 103:275–280PubMedCrossRefGoogle Scholar
  220. Sandoval KE, Witt KA (2008) Blood-brain barrier tight junction permeability and ischemic stroke. Neurobiol Dis 32:200–219PubMedCrossRefGoogle Scholar
  221. Saransaari P, Oja SS (2005) GABA release modified by adenosine receptors in mouse hippocampal slices under normal and ischemic conditions. Neurochem Res 30:467–473PubMedCrossRefGoogle Scholar
  222. Schiffmann SN, Jacobs O, Vanderhaeghen JJ (1991) Striatal restricted adenosine A2 receptor (RDC8) is expressed by enkephalin but not by substance P neurons: an in situ hybridization histochemistry study. J Neurochem 57:1062–1067PubMedCrossRefGoogle Scholar
  223. Schrader WP, West CA, Strominger NL (1987) Localization of adenosine deaminase and adenosine deaminase complexing protein in rabbit brain. J Histochem Cytochem 35:443–451PubMedCrossRefGoogle Scholar
  224. Schwartz-Bloom RD, Sah R (2001) Gamma-Aminobutyric acid(A) neurotransmission and cerebral ischemia. J Neurochem 77:353–371PubMedCrossRefGoogle Scholar
  225. Schwarzschild MA, Chen JF, Ascherio A (2002) Caffeinated clues and the promise of adenosine A(2A) antagonists in PD. Neurology 58:1154–1160PubMedCrossRefGoogle Scholar
  226. Sciotti VM, Roche FM, Grabb MC, Van Wylen DG (1992) Adenosine receptor blockade augments interstitial fluid levels of excitatory amino acids during cerebral ischemia. J Cereb Blood Flow Metab 12:646–655PubMedCrossRefGoogle Scholar
  227. Sebastião AM, Cunha RA, de Mendonca A, Ribeiro JA (2000) Modification of adenosine modulation of synaptic transmission in the hippocampus of aged rats. Br J Pharmacol 131:1629–1634PubMedCrossRefGoogle Scholar
  228. Sebastião AM, de Mendonca A, Moreira T, Ribeiro JA (2001) Activation of synaptic NMDA receptors by action potential-dependent release of transmitter during hypoxia impairs recovery of synaptic transmission on reoxygenation. J Neurosci 21:8564–8571PubMedGoogle Scholar
  229. Seif-el-Nasr M, Khattab M (2002) Influence of inhibition of adenosine uptake on the gamma-aminobutyric acid level of the ischemic rat brain. Arzneimittelforschung 52:353–357PubMedGoogle Scholar
  230. Sheardown MJ, Knutsen LJS (1996) Unexpected neuroprotection observed with the adenosine A2A receptor agonist CGS21680. Drug Dev Res 39:108–114CrossRefGoogle Scholar
  231. Shen H-Y, Lusardi TA, Williams-Karnesky RL, Lan J-Q, Poulsen DJ, Boison D (2011) Adenosine kinase determines the degree of brain injury after ischemic stroke in mice. J Cereb Blood Flow Metab 31(7):1648–59Google Scholar
  232. Shrager P, Novakovic SD (1995) Control of myelination, axonal growth, and synapse formation in spinal cord explants by ion channels and electrical activity. Brain Res Dev Brain Res 88:68–78PubMedCrossRefGoogle Scholar
  233. Simpson RE, O’Regan MH, Perkins LM, Phillis JW (1992) Excitatory transmitter amino acid release from the ischemic rat cerebral cortex: effects of adenosine receptor agonists and antagonists. J Neurochem 58:1683–1690PubMedCrossRefGoogle Scholar
  234. Sitkovsky MV, Lukashev D, Apasov S, Kojima H, Koshiba M, Caldwell C, Ohta A, Thiel M (2004) Physiological control of immune response and inflammatory tissue damage by hypoxia-inducible factors and adenosine A2A receptors. Ann Rev Immunol 22:657–682CrossRefGoogle Scholar
  235. Somjen GG (2001) Mechanisms of spreading depression and hypoxic spreading depression-like depolarization. Physiol Rev 81:1065–1096PubMedGoogle Scholar
  236. Stevens B, Porta S, Haak LL, Gallo V, Fields RD (2002) Adenosine: a neuron-glial transmitter promoting myelination in the CNS in response to action potentials. Neuron 36:855–868PubMedCrossRefGoogle Scholar
  237. Stoll G, Jander S, Schroeter M (1998) Inflammation and glial responses in ischemic brain lesions. Prog Neurobiol 56:149–171PubMedCrossRefGoogle Scholar
  238. Stone TW, Behan WM (2007) Interleukin-1beta but not tumor necrosis factor-alpha potentiates neuronal damage by quinolinic acid: protection by an adenosine A2A receptor antagonist. J Neurosci Res 85:1077–1085PubMedCrossRefGoogle Scholar
  239. Sutherland GR, Peeling J, Lesiuk HJ, Brownstone RM, Rydzy M, Saunders JK, Geiger JD (1991) The effects of caffeine on ischemic neuronal injury as determined by magnetic resonance imaging and histopathology. Neuroscience 42:171–182PubMedCrossRefGoogle Scholar
  240. Svenningsson P, Nomikos GG, Ongini E, Fredholm BB (1997) Antagonism of adenosine A2A receptors underlies the behavioural activating effect of caffeine and is associated with reduced expression of messenger RNA for NGFI-A and NGFI-B in caudate-putamen and nucleus accumbens. Neuroscience 79:753–764PubMedCrossRefGoogle Scholar
  241. Svenningsson P, Le Moine C, Fisone G, Fredholm BB (1999) Distribution, biochemistry and function of striatal adenosine A2A receptors. Prog Neurobiol 59:355–396PubMedCrossRefGoogle Scholar
  242. Takagi Y, Nozaki K, Sugino T, Hattori I, Hashimoto N (2000) Phosphorylation of c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase after transient forebrain ischemia in mice. Neurosci Lett 294:117–120PubMedCrossRefGoogle Scholar
  243. Tanaka E, Yasumoto S, Hattori G, Niiyama S, Matsuyama S, Higashi H (2001) Mechanisms underlying the depression of evoked fast EPSCs following in vitro ischemia in rat hippocampal CA1 neurons. J Neurophysiol 86:1095–1103PubMedGoogle Scholar
  244. Tatlisumak T, Takano K, Carano RA, Miller LP, Foster AC, Fisher M (1998) Delayed treatment with an adenosine kinase inhibitor, GP683, attenuates infarct size in rats with temporary middle cerebral artery occlusion. Stroke 29:1952–1958PubMedCrossRefGoogle Scholar
  245. Trincavelli ML, Tuscano D, Cecchetti P, Falleni A, Benzi L, Klotz KN, Gremigni V, Cattabeni F, Lucacchini A, Martini C (2000) Agonist-induced internalization and recycling of the human A(3) adenosine receptors: role in receptor desensitization and resensitization. J Neurochem 75:1493–1501PubMedCrossRefGoogle Scholar
  246. Trincavelli ML, Tuscano D, Marroni M, Falleni A, Gremigni V, Ceruti S, Abbracchio MP, Jacobson KA, Cattabeni F, Martini C (2002) A3 adenosine receptors in human astrocytoma cells: agonist-mediated desensitization, internalization, and down-regulation. Mol Pharmacol 62:1373–1384PubMedCrossRefGoogle Scholar
  247. Trincavelli ML, Marroni M, Tuscano D, Ceruti S, Mazzola A, Mitro N, Abbracchio MP, Martini C (2004) Regulation of A2B adenosine receptor functioning by tumour necrosis factor a in human astroglial cells. J Neurochem 91:1180–1190PubMedCrossRefGoogle Scholar
  248. Trincavelli ML, Melani A, Guidi S, Cipriani S, Pedata F, Martini C (2008a) Regulation of A2A adenosine receptor expression and functioning following permanent focal ischemia in rat brain. J Neurochem 104:479–490PubMedGoogle Scholar
  249. Trincavelli ML, Tonazzini I, Montali M, Abbracchio MP, Martini C (2008b) Short-term TNF-Alpha treatment induced A2B adenosine receptor desensitization in human astroglial cells. J Cell Biochem 104:150–161PubMedCrossRefGoogle Scholar
  250. Turcáni P, Turèáni M (2001) Effect of propentofylline on cerebral blood flow in a gerbil focal cerebral ischemia. J Neurol Sci 183:57–60PubMedCrossRefGoogle Scholar
  251. Turner CP, Yan H, Schwartz M, Othman T, Rivkees SA (2002) A1 adenosine receptor activation induces ventriculomegaly and white matter loss. Neuroreport 13:1199–1204PubMedCrossRefGoogle Scholar
  252. Turner CP, Seli M, Ment L, Stewart W, Yan H, Johansson B, Fredholm BB, Blackburn M, Rivkees SA (2003) A1 adenosine receptors mediate hypoxia-induced ventriculomegaly. Proc Natl Acad Sci USA 100:11718–11722PubMedCrossRefGoogle Scholar
  253. Van Galen PJ, van Bergen AH, Gallo-Rodriguez C, Melman N, Olah ME, IJzerman AP, Stiles GL, Jacobson KA (1994) A binding site model and structure-activity relationships for the rat A3 adenosine receptor. Mol Pharmacol 45:1101–1111Google Scholar
  254. Volpini R, Costanzi S, Lambertucci C, Taffi S, Vittori S, Klotz KN, Cristalli G (2002) N(6)-alkyl-2-alkynyl derivatives of adenosine as potent and selective agonists at the human adenosine A(3) receptor and a starting point for searching A(2B) ligands. J Med Chem 45:3271–3279PubMedCrossRefGoogle Scholar
  255. Volpini R, Dal Ben D, Lambertucci C, Taffi S, Vittori S, Klotz KN, Cristalli G (2007) N6-methoxy-2-alkynyladenosine derivatives as highly potent and selective ligands at the human A3 adenosine receptor. J Med Chem 50:1222–1230PubMedCrossRefGoogle Scholar
  256. von Arnim CA, Timmler M, Ludolph AC, Riepe MW (2000) Adenosine receptor up-regulation: initiated upon preconditioning but not upheld. Neuroreport 11:1223–1226CrossRefGoogle Scholar
  257. von Arnim CA, Spoelgen R, Peltan ID, Deng M, Courchesne S, Koker M, Matsui T, Kowa H, Lichtenthaler SF, Irizarry MC, Hyman BT (2006) GGA1 acts as a spatial switch altering amyloid precursor protein trafficking and processing. J Neurosci 26:9913–9922CrossRefGoogle Scholar
  258. von Lubitz DK (1999) Adenosine and cerebral ischemia: therapeutic future or death of a brave concept? Eur J Pharmacol 371:85–102CrossRefGoogle Scholar
  259. von Lubitz DK, Marangos PJ (1990) Cerebral ischemia in gerbils: postischemic administration of cyclohexyl adenosine and 8-sulfophenyl-theophylline. J Mol Neurosci 2:53–59CrossRefGoogle Scholar
  260. von Lubitz DK, Dambrosia JM, Kempski O, Redmond DJ (1988) Cyclohexyl adenosine protects against neuronal death following ischemia in the CA1 region of gerbil hippocampus. Stroke 19:1133–1139CrossRefGoogle Scholar
  261. von Lubitz DK, Lin RC, Melman N, Ji XD, Carter MF, Jacobson KA (1994a) Chronic administration of selective adenosine A1 receptor agonist or antagonist in cerebral ischemia. Eur J Pharmacol 256:161–167CrossRefGoogle Scholar
  262. von Lubitz DK, Lin RC, Popik P, Carter MF, Jacobson KA (1994b) Adenosine A3 receptor stimulation and cerebral ischemia. Eur J Pharmacol 263:59–67CrossRefGoogle Scholar
  263. von Lubitz DK, Lin RC, Jacobson KA (1995) Cerebral ischemia in gerbils: effects of acute and chronic treatment with adenosine A2A receptor agonist and antagonist. Eur J Pharmacol 287:295–302CrossRefGoogle Scholar
  264. von Lubitz DK, Lin RC, Paul IA, Beenhakker M, Boyd M, Bischofberger N, Jacobson KA (1996) Postischemic administration of adenosine amine congener (ADAC): analysis of recovery in gerbils. Eur J Pharmacol 1996:171–179CrossRefGoogle Scholar
  265. von Lubitz DK, Ye W, McClellan J, Lin RC (1999) Stimulation of adenosine A3 receptors in cerebral ischemia. Neuronal death, recovery, or both? Ann N Y Acad Sci 890:93–106CrossRefGoogle Scholar
  266. von Lubitz DK, Simpson KL, Lin RC (2001) Right thing at a wrong time? Adenosine A3 receptors and cerebroprotection in stroke. Ann N Y Acad Sci 939:85–96CrossRefGoogle Scholar
  267. Wei CJ, Li W, Chen JF (2011) Normal and abnormal functions of adenosine receptors in the central nervous system revealed by genetic knockout studies. Biochim Biophys Acta 1808:1358–1379PubMedCrossRefGoogle Scholar
  268. Wentz CT, Magavi SS (2009) Caffeine alters proliferation of neuronal precursors in the adult hippocampus. Neuropharmacology 56:994–1000PubMedCrossRefGoogle Scholar
  269. Weyler S, Fülle F, Diekmann M, Schumacher B, Hinz S, Klotz KN, Müller CE (2006) Improving potency, selectivity, and water solubility of adenosine A1 receptor antagonists: xanthines modified at position 3 and related pyrimido[1,2,3-cd]purinediones. Chem Med Chem 1(8):891–902PubMedGoogle Scholar
  270. White PJ, Rose’Meyer RB, Hope W (1996) Functional characterization of adenosine receptors in the nucleus tractus solitarius mediating hypotensive responses in the rat. Br J Pharmacol 117:305–308PubMedCrossRefGoogle Scholar
  271. Wu DC, Ye W, Che XM, Yang GY (2000) Activation of mitogen-activated protein kinases after permanent cerebral artery occlusion in mouse brain. J Cereb Blood Flow Metab 20:1320–1330PubMedCrossRefGoogle Scholar
  272. Xi J, McIntosh R, Shen X, Lee S, Chanoit G, Criswell H, Zvara DA, Xu Z (2009) Adenosine A2A and A2B receptors work in concert to induce a strong protection against reperfusion injury in rat hearts. J Mol Cell Cardiol 47(5):684–690Google Scholar
  273. Yao Y, Sei Y, Abbracchio MP, Jiang JL, Kim YC, Jacobson KA (1997) Adenosine A3 receptor agonists protect HL-60 and U-937 cells from apoptosis induced by A3 antagonists. Biochem Biophys Res Commun 232:317–322PubMedCrossRefGoogle Scholar
  274. Yoshida M, Nakakimura K, Cui YJ, Matsumoto M, Sakabe T (2004) Adenosine A(1) receptor antagonist and mitochondrial ATP-sensitive potassium channel blocker attenuate the tolerance to focal cerebral ischemia in rats. J Cereb Blood Flow Metab 24:771–779PubMedCrossRefGoogle Scholar
  275. Yu L, Frith MC, Suzuki Y, Peterfreund RA, Gearan T, Sugano S, Schwarzschild MA, Weng Z, Fink JS, Chen JF (2004a) Characterization of genomic organization of the adenosine A(2A) receptor gene by molecular and bioinformatics analyses. Brain Res 1000:156–173PubMedCrossRefGoogle Scholar
  276. Yu L, Huang Z, Mariani J, Wang Y, Moskowitz M, Chen JF (2004b) Selective inactivation or reconstitution of adenosine A2A receptors in bone marrow cells reveals their significant contribution to the development of ischemic brain injury. Nat Med 10:1081–1087PubMedCrossRefGoogle Scholar
  277. Zetterstrom T, Fillenz M (1990) Adenosine agonists can both inhibit and enhance in vivo striatal dopamine release. Eur J Pharmacol 180:137–143PubMedCrossRefGoogle Scholar
  278. Zhang D, Xiong W, Albensi BC, Parkinson FE (2011) Expression of human equilibrative nucleoside transporter 1 in mouse neurons regulates adenosine levels in physiological and hypoxic-ischemic conditions. J Neurochem 118:4–11PubMedCrossRefGoogle Scholar
  279. Zhao Z, Francis C, Ravid K (1999) Characterization of the mouse A3 adenosine receptor gene: exon/intron organization and promoter activity. Genomics 57:152–155PubMedCrossRefGoogle Scholar
  280. Zhou JG, Meno JR, Hsu SS, Winn HR (1994) Effects of theophylline and cyclohexyladenosine on brain injury following normo- and hyperglycemic ischemia: a histopathologic study in the rat. J Cereb Blood Flow Metab 14:166–173PubMedCrossRefGoogle Scholar
  281. Zhou AM, Li WB, Li QJ, Liu HQ, Feng RF, Zhao HG (2004) A short cerebral ischemic preconditioning up-regulates adenosine receptors in the hippocampal CA1 region of rats. Neurosci Res 48:397–404PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Felicita Pedata
    • 1
  • Anna Maria Pugliese
    • 1
  • Francesca Corti
    • 1
  • Alessia Melani
    • 1
  1. 1.Department of Preclinical and Clinical PharmacologyUniversity of FlorenceFlorenceItaly

Personalised recommendations