Adenosine Receptors and Neurological Disease: Neuroprotection and Neurodegeneration

  • Trevor W. Stone
  • Stefania  Ceruti
  • Mariapia P. Abbracchio
Chapter
First Online:
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 193)

Abstract

Adenosine receptors modulate neuronal and synaptic function in a range of ways that may make them relevant to the occurrence, development and treatment of brain ischemic damage and degenerative disorders. A1 adenosine receptors tend to suppress neural activity by a predominantly presynaptic action, while A2A adenosine receptors are more likely to promote transmitter release and postsynaptic depolarization. A variety of interactions have also been described in which adenosine A1 or A2 adenosine receptors can modify cellular responses to conventional neurotransmitters or receptor agonists such as glutamate, NMDA, nitric oxide and P2 purine receptors. Part of the role of adenosine receptors seems to be in the regulation of inflammatory processes that often occur in the aftermath of a major insult or disease process. All of the adenosine receptors can modulate the release of cytokines such as interleukins and tumor necrosis factor-α from immune-competent leukocytes and glia. When examined directly as modifiers of brain damage, A1 adenosine receptor (AR) agonists, A2AAR agonists and antagonists, as well as A3AR antagonists, can protect against a range of insults, both in vitro and in vivo. Intriguingly, acute and chronic treatments with these ligands can often produce diametrically opposite effects on damage outcome, probably resulting from adaptational changes in receptor number or properties. In some cases molecular approaches have identified the involvement of ERK and GSK-3β pathways in the protection from damage. Much evidence argues for a role of adenosine receptors in neurological disease. Receptor densities are altered in patients with Alzheimer’s disease, while many studies have demonstrated effects of adenosine and its antagonists on synaptic plasticity in vitro, or on learning adequacy in vivo. The combined effects of adenosine on neuronal viability and inflammatory processes have also led to considerations of their roles in Lesch–Nyhan syndrome, Creutzfeldt–Jakob disease, Huntington’s disease and multiple sclerosis, as well as the brain damage associated with stroke. In addition to the potential pathological relevance of adenosine receptors, there are earnest attempts in progress to generate ligands that will target adenosine receptors as therapeutic agents to treat some of these disorders.

Keywords

Neuroprotection Neurodegeneration Ischaemia Alzheimer’s disease β-amyloid Huntington’s disease Parkinson’s disease Neurotoxicity Aging Stroke Lesch-Nyhan syndrome Multiple sclerosis Creutzfeldt-Jacob syndrome Prion disease Acute administration Chronic administration Receptor up-regulation Receptor down-regulation 

Abbreviations

ADAC

Adenosine amine congener

AMP

Adenosine monophosphate

AR

Adenosine receptor

BDNF

Brain-derived neurotrophic factor

BIIP20

S-( − )-8-(3-Oxocyclopentyl)-1,3-dipropyl-7H-purine-2,6-dione

cAMP

Cyclic adenosine monophosphate

CCPA

2-Chloro-N 6-cyclopentyladenosine

CGS15943

5-Amino-9-chloro-2-(2-furyl)-1,2,4-triazolo[1,5-c]quinazoline

CGS21680

2-[4-(2-Carboxyethyl)-phenylethylamino]-5 ′ N-ethyl-carbox amido-adenosine

CHA

N 6-Cyclohexyladenosine

CJD

Creutzfeldt–Jakob disease

Cl-IB-MECA

2-Chloro-N 6-(3-iodobenzyl)adenosine-5 ′ -N-methyluronamide

CNS

Central nervous system

CP66,713

4-Amino-1-phenyl[1,2,4]-triazolo[4,3-a]quinoxaline

CPA

Cyclopentyl adenosine

8-CPT

8-Cyclopentyltheophylline

CREB

Cyclic AMP responsive element binding protein

CSC

8-(3-Chloro styryl)caffeine

DMPX

3,7-Dimethyl-1-propargylxanthine

DPCPX

8-Cyclopentyl-1,3-dipropylxanthine

EAE

Allergic encephalomyelitis

ERK1/2

Extracellular signal-regulated kinases 1 and 2

GABA

Gamma-aminobutyric acid

HD

Huntington’s disease

HGPRT

Hypoxanthine-guanine phosphoribosyltransferase

IB–MECA

N 6-(3-Iodobenzyl)adenosine-5 ′ -N-methyluronamide

IL

Interleukin

KFM19

RS-( − )-8-(3-oxocyclopentyl)-1,3-dipropyl-7H-purine-2,6-dione

LNS

Lesch–Nyhan syndrome

MAP-2

Microtubule-associated protein 2

MAPK

Mitogen-activated protein kinases

MCAo

Middle cerebral artery occlusion

MPTP

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

MRS2179

N 6-Methyl-2 ′ -deoxyadenosine-3 ′ , 5 ′ -bisphosphate

MRS1706

N-(4-Acetylphenyl)-2-[4-(2,3,6,7-tetrahydro-2,6-dioxo-1,3- dipropyl-1H-purin-8-yl)-phenoxy]acetamide

MS

Multiple sclerosis

NBTI

Nitrobenzylthioinosine

NECA

5 ′ -N-Ethylcarboxamidoadenosine

NGF

Nerve growth factor

NMDA

N-Methyl-d-aspartate

3-NP

3-Nitro-propionic acid

PKC

Protein kinase C

PLC

Phospholipase C

R-PIA

R-Phenylisopropyladenosine

SAH

S-Adenosylhomocysteine

SCH58261

7-(2-Phenylethyl)-5-amino-2-(2-furyl)-pyrazolo-[4,3-e]-1,2,4-triazolo[1,5-c]-pyrimidine

TNF-α

Tumor necrosis factor alpha

Trk

Tropomyosin-related kinase

ZM241385

4-(2-[7-Amino-2-(2-furyl)(1,2,4)-triazolo(2,3-a)-(1,3,5)triazin-5-yl-amino]ethyl)phenol

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References

  1. Abbracchio MP, Fogliatto G, Paoletti AM, Rovati GE, Cattabeni F (1992) Prolonged invitro exposure of rat-brain slices to adenosine-analogs: selective desensitization of adenosine-A(1) but not adenosine-A(2) receptors. Eur J Pharmacol 227:317–324PubMedCrossRefGoogle Scholar
  2. Abbracchio MP, Rainaldi G, Giammarioli AM, Ceruti S, Brambilla R, Cattabeni F, Barbieri D, Franceschi C, Jacobson KA, Malorni W (1997) The A3 adenosine receptor mediates cell spreading, reorganisation of actin cytoskeleton and distribution of Bcl-x(L): studies in human astroglioma cells. Biochem Biophys Res Commun 241:297–304PubMedCrossRefGoogle Scholar
  3. Abbracchio MP, Ceruti S, Brambilla R, Barbieri D, Camurri A, Franceschi C, Giammarioli AM, Jacobson KA, Cattabeni F, Malorni W (1998) Adenosine A3 receptors and viability of astrocytes. Drug Dev Res 45:379–386CrossRefGoogle Scholar
  4. Abbracchio MP, Burnstock G, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Knight GE, Fumagalli M, Gachet C, Jacobson KA, Weisman GA (2006) International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol Rev 58:281–341PubMedCrossRefGoogle Scholar
  5. Aden U, Halldner L, Lagercrantz H, Dalmau I, Ledent C, Fredholm BB (2003) Aggravated brain damage after hypoxic ischemia in immature adenosine A(2A) knockout mice. Stroke 34: 739–744PubMedCrossRefGoogle Scholar
  6. Albasanz JL, Perez S, Barrachina M, Ferrer I, Martin M (2008) Up-regulation of adenosine receptors in the frontal cortex in Alzheimer’s disease. Brain Pathol 18:211–219PubMedCrossRefGoogle Scholar
  7. Alfinito PD, Wang SP, Manzino L, Rijhsinghani S, Zeevalk GD, Sonsalla PK (2003) Adenosinergic protection of dopaminergic and GABAergic neurons against mitochondrial inhibition through receptors located in the substantia nigra and striatum, respectively. J Neurosci 23:10982–10987PubMedGoogle Scholar
  8. Andiné P, Rudolphi KA, Fredholm BB, Hagberg H (1990) Effect of propentofylline (HWA285) in extracellular purines and excitatory amino acids in CA1 of rat hippocampus during transient ischaemia. Br J Pharmacol 100:814–818PubMedGoogle Scholar
  9. Angelucci ME, Cesário C, Hiroi RH, Rosalen PL, Da Cunha C (2002) Effects of caffeine on learning and memory in rats tested in the Morris water maze. Braz J Med Biol Res 35: 1201–1208PubMedCrossRefGoogle Scholar
  10. Angulo E, Casado V, Mallol J, Canela EI, Vinals F, Ferrer I, Lluis C, Franco R (2003) A(1) adenosine receptors accumulate in neurodegenerative structures in Alzheimer disease and mediate both amyloid precursor protein processing and tau phosphorylation and translocation. Brain Pathol 13:440–451PubMedCrossRefGoogle Scholar
  11. Appel E, Kazimirsky G, Ashkenazi E, Kim SG, Jacobson KA, Brodie C (2001) Roles of BCL-2 an caspase 3 in the adenosine A3 receptor-induced apoptosis. J Mol Neurosci 17:285–292PubMedCrossRefGoogle Scholar
  12. Araki T, Kato H, Kanai Y, Kogure K (1993) Selective changes of neurotransmitter receptors in middle-aged gerbil brain. Neurochem Intern 23:541–548CrossRefGoogle Scholar
  13. Arendash GW, Schleif W, Rezai-Zadeh K, Jackson EK, Zacharia LC, Cracchiolo JR, Shippy D, Tan J (2006) Caffeine protects Alzheimer’s mice against cognitive impairment and reduces brain β-amyloid production. Neuroscience 142:941–952PubMedCrossRefGoogle Scholar
  14. Arvin B, Neville LF, Pan J, Roberts PJ (1989) 2-Chloroadenosine attenuates kainic acid-induced toxicity within the rat striatum: relationship to release of glutamate and Ca2 + influx. Br J Pharmacol 98:225–235PubMedGoogle Scholar
  15. Baraldi PG, Tabrizi MA, Gessi S, Borea PA (2008) Adenosine receptor antagonists: translating medicinal chemistry and pharmacology into clinical utility. Chem Rev 108:238–263PubMedCrossRefGoogle Scholar
  16. Barnes CR, Mandell GL, Carper HT, Luong S, Sullivan GW (1995) Adenosine modulation of TNFα-induced neutrophil activation. Biochem Pharmacol 50:1851–1857PubMedCrossRefGoogle Scholar
  17. Bartrup JT, Stone TW (1990) Activation of NMDA receptor-coupled channels suppresses the inhibitory action of adenosine on hippocampal slices. Brain Res 530:330–334PubMedCrossRefGoogle Scholar
  18. Bartrup JT, Addae JI, Stone TW (1991) Interaction between adenosine and excitatory agonists in rat hippocampal slices. Brain Res 564:323–327PubMedCrossRefGoogle Scholar
  19. Bauer A, Zilles K, Matusch A, Holzmann C, Riess O, von Horsten S (2005) Regional and subtype selective changes of neurotransmitter receptor density in a rat transgenic for the Huntington’s disease mutation. J Neurochem 94:639–650PubMedCrossRefGoogle Scholar
  20. Beal MF, Kowall NW, Ellison DW, Mazurek MF, Swartz KJ, Martin JB (1986) Replication of the neurochemical characteristics of Huntington’s disease by quinolinic acid. Nature 321:168–171PubMedCrossRefGoogle Scholar
  21. Beal MF, Ferrante RJ, Swartz KJ, Kowall NW (1991) Chronic quinolinic acid lesions in rats closely resemble Huntington’s disease. J Neurosci 11:1649–1659PubMedGoogle Scholar
  22. Behrens PF, Franz P, Woodman B, Lindenberg KS, Landwehrmeyer GB (2002) Impaired glutamate transport and glutamate–glutamine cycling: downstream effects of the Huntington mutation. Brain 125:1908–1922PubMedCrossRefGoogle Scholar
  23. Bensadoun JC, de Almeida LP, Dréano M, Aebischer P, Déglon N (2001) Neuroprotective effect of interleukin-6 and IL6/IL6R chimera in the quinolinic acid rat model of Huntington’s syndrome. Eur J Neurosci 14:1753–1761PubMedCrossRefGoogle Scholar
  24. Bertelli M, Cecchin S, Lapucci C, Jacomelli G, Jinnah HA, Pandolfo M, Micheli V (2006) Study of the adenosinergic system in the brain of HPRT knockout mouse (Lesch–Nyhan disease). Clin Chim Acta 373:104–107PubMedCrossRefGoogle Scholar
  25. Bischofberger N, Jacobson KA, von Lubitz DKJE (1997) Adenosine A(1) receptor agonists as clinically viable agents for treatment of ischemic brain disorders. Ann NY Acad Sci 825:23–29PubMedCrossRefGoogle Scholar
  26. Blum D, Gall D, Galas MC, d’Alcantara P, Bantubungi K, Schiffmann, SN (2002) The adenosine A(1) receptor agonist adenosine amine congener exerts a neuroprotective effect against the development of striatal lesions and motor impairments in the 3-nitropropionic acid model of neurotoxicity. J Neurosci 22:9122–9133PubMedGoogle Scholar
  27. Blum D, Galas MC, Pintor A, Brouillet E, Ledent C, Muller CE, Bantubungi K, Galluzzo M, Gall D, Cuvelier L, Rolland AS, Popoli P, Schiffmann SN (2003a) A dual role of adenosine A(2A) receptors in 3-nitropropionic acid-induced striatal lesions: implications for the neuroprotective potential of A(2)A antagonists. J Neurosci 23:5361–5369PubMedGoogle Scholar
  28. Blum D, Hourez R, Galas MC, Popoli P, Schiffmann SN (2003b) Adenosine receptors and Huntington’s disease: implications for pathogenesis and therapeutics. Lancet Neurol 2:366–374PubMedCrossRefGoogle Scholar
  29. Bona E, Adén U, Gilland E, Fredholm BB, Hagberg H (1997) Neonatal cerebral hypoxia-ischaemia: the effect of adenosine receptor antagonists. Neuropharmacology 9:1327–1338CrossRefGoogle Scholar
  30. Bours MJ, Swennen EL, Di Virgilio F, Cronstein BN, Dagnelie PC (2006) Adenosine 5′-triphosphate and adenosine as endogenous signaling molecules in immunity and inflammation. Pharmacol Ther 112:358–404PubMedCrossRefGoogle Scholar
  31. Brambilla R, Cottini L, Fumagalli M, Ceruti S, Abbracchio MP (2003) Blockade of A2A adenosine receptors prevents basic fibroblast growth factor-induced reactive astrogliosis in rat striatal primary astrocytes. Glia 43:190–194PubMedCrossRefGoogle Scholar
  32. Bridges AJ, Bruns RF, Ortwine DF, Priebe SR, Szotek DL, Trivedi BK (1988) N 6-[2-(3,5-Dimethoxyphenyl)-2-(2-methylphenyl)-ethyl]adenosine and its uronamide derivatives. Novel adenosine agonists and antagonists with both high affinity and high selectivity for the adenosine A2 receptor. J Med Chem 31:1282–1285PubMedCrossRefGoogle Scholar
  33. Broadley KJ (2000) Drugs modulating adenosine receptors as potential therapeutic agents for cardiovascular diseases. Exp Opin Ther Pat 10:1669–1692CrossRefGoogle Scholar
  34. Brown SJ, James S, Reddington M, Richardson PJ (1990) Both A1 and A2A purine receptors regulate striatal acetylcholine release. J Neurochem 55:31–38PubMedCrossRefGoogle Scholar
  35. Bullough DA, Magill MJ, Firestein GS, Mullane KM (1995) Adenosine activates A2 receptors to inhibit neutrophil adhesion and injury to isolated cardiac myocytes. J Immunol 155:2579–2586PubMedGoogle Scholar
  36. Burkey TH, Webster RD (1993) Adenosine inhibits fMLP-stimulated adherence and superoxide anion generation by human neutrophils at an early step in signal transduction. Biochem Biophys Acta 1175:312–318PubMedCrossRefGoogle Scholar
  37. Butcher SP, Bullock R, Graham DI, McCulloch J (1990) Correlation between amino acid release and neuropathologic outcome in rat brain following middle cerebral artery occlusion. Stroke 21:1727–1733PubMedGoogle Scholar
  38. Cain BS, Meldrum DR, Dinarello CA, Meng X, Banerjee A, Harken AH (1998) Adenosine reduces cardiac TNF-α production and human myocardial injury following ischaemia-reperfusion. J Surg Res 76:117–123PubMedCrossRefGoogle Scholar
  39. Canals M, Marcellino D, Fanelli F, Ciruela F, de Benedetti P, Goldberg SR, Neve K, Fuxe K, Agnati LF, Woods AS, Ferré S, Lluis C, Bouvier M, Franco R (2003) Adenosine A2A-dopamine D2 receptor–receptor heteromerization: qualitative and quantitative assessment by fluorescence and bioluminescence energy transfer. J Biol Chem 278:46741–46749PubMedCrossRefGoogle Scholar
  40. Canals M, Angulo E, Casado V, Canela EI, Mallol J, Vinals F, Staines W, Tinner B, Hillion J, Agnati L, Fuxe K, Ferre S, Lluis C, Franco R (2005) Molecular mechanisms involved in the adenosine A(1) and A(2A) receptor-induced neuronal differentiation in neuroblastoma cells and striatal primary cultures. J Neurochem 92:337–348PubMedCrossRefGoogle Scholar
  41. Cantor SL, Zornow MH, Miller LP, Yaksh TL (1992) The effect of cyclohexyladenosine on the periischemic increases of hippocampal glutamate and glycine in the rabbit. J Neurochem 59:1884–1892PubMedCrossRefGoogle Scholar
  42. Cargnoni A, Ceconi C, Boraso A, Bernocchi P, Monopoli A, Curello S, Ferrari R (1999) Role of A2A receptors in the modulation of myocardial reperfusion damage. J Cardiovasc Pharmacol 33:883–893PubMedCrossRefGoogle Scholar
  43. Carlson NG, Wieggel WA, Chen J, Bacchi A, Rogers SW, Gahring LC (1999) Inflammatory cytokines IL-1α, IL-1β, IL-6, and TNF-α impart neuroprotection to an excitotoxin through distinct pathways. J Immunol 163:3963–3968PubMedGoogle Scholar
  44. Casati C, Forlani A, Lozza G, Monopoli A (1997) Hemodynamic changes do not mediate the cardioprotection induced by the A1 adenosine receptor agonist CCPA in the rabbit. Pharmacol Res 35:51–55PubMedCrossRefGoogle Scholar
  45. Cassada DC, Tribble CG, Kaza AK, Fiser SM, Long SM, Linden J, Rieger JM, Kron IL, Kern JA (2001a) Adenosine analogue reduces spinal cord reperfusion injury in a time-dependent fashion. Surgery 130:230–235PubMedCrossRefGoogle Scholar
  46. Cassada DC, Tribble CG, Laubach VE, Nguyen BN, Rieger JM, Linden J, Kaza AK, Long SM, Kron IL, Kern JA (2001b) An adenosine A(2A) agonist, ATL-146e, reduces paralysis and apoptosis during rabbit spinal cord reperfusion. J Vasc Surg 34:482–488PubMedCrossRefGoogle Scholar
  47. Cassada DC, Tribble CG, Long SM, Laubach VE, Kaza AK, Linden J, Nguyen BN, Rieger JM, Fiser SM, Kron IL, Kern JA (2002) Adenosine A2(A) analogue ATL-146e reduces systemic tumor necrosing factor-α and spinal cord capillary platelet-endothelial cell adhesion molecule-1 expression after spinal cord ischemia. J Vasc Surg 35, 994–998PubMedCrossRefGoogle Scholar
  48. Chen JF, Huang Z, Ma J, Zhu J, Moratalla R, Standaert D, Moskowitz MA, Fink JS, Schwarzschild MA (1999) A2A adenosine receptor deficiency attenuates brain injury induced by transient focal ischaemia in mice. J Neurosci 19:9192–9200PubMedGoogle Scholar
  49. Chen G-J, 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
  50. Chiang MC, Lee YC, Huang CL, Chern YJ (2005) cAMP-response element-binding protein contributes to suppression of the A(2A) adenosine receptor promoter by mutant huntingtin with expanded polyglutamine residues. J Biol Chem 280:14331–14340PubMedCrossRefGoogle Scholar
  51. Chou SY, Lee YC, Chen HM, Chiang MC, Lai HL, Chang HH, Wu YC, Sun CN, Chien CL, Lin YS, Wang SC, Tung YY, Chang C, Chern YJ (2005) CGS21680 attenuates symptoms of Huntington’s disease in a transgenic mouse model. J Neurochem 93:310–320PubMedCrossRefGoogle Scholar
  52. Chowdhury M, Fillenz M (1991) Presynaptic adenosine A2 and NMDA receptors regulate dopamine synthesis in rat striatal synaptosomes. J Neurochem 56:1783–1788PubMedCrossRefGoogle Scholar
  53. Ciccarelli R, D’Alimonte I, Ballerini P, D’Auro M, Nargi E, Buccella S, Di Iorio P, Bruno V, Nicoletti F, Caciagli F (2007) Molecular signalling mediating the protective effect of A(1) adenosine and mGlu3 metabotropic glutamate receptor activation against apoptosis by oxygen/glucose deprivation in cultured astrocytes. Mol Pharmacol 71:1369–1380PubMedCrossRefGoogle Scholar
  54. Coelho JE, Rebola N, Fragata I, Ribeiro JA, De Mendonca A, Cunha RA (2006) Hypoxia-induced desensitization and internalization of adenosine A(1) receptors in the rat hippocampus. Neuroscience 138:1195–1203PubMedCrossRefGoogle Scholar
  55. Connick JH, Stone TW (1986) The effects of kainate, β-kainate and quinolinic acids on the release of endogenous amino acids from rat brain slices. Biochem Pharmacol 35:3631–3635PubMedCrossRefGoogle Scholar
  56. Connick JH, Stone TW (1989) Quinolinic acid neurotoxicity: protection by intracerebral phenylisopropyl adenosine (PIA) and potentiation by hypotension. Neurosci Lett 101:191–196PubMedCrossRefGoogle Scholar
  57. Corodimas KP, Tomita H (2001) Adenosine A1 receptor activation selectively impairs the acquisition of contextual fear conditioning in rats. Behav Neurosci 115(6):1283–1290PubMedCrossRefGoogle Scholar
  58. Corradetti R, Lo Conte G, Moroni F, Passani MB, Pepeu G (1984) Adenosine decreases aspartate and glutamate release from rat hippocampal slices. Eur J Pharmacol 140:19–26CrossRefGoogle Scholar
  59. Corset V, Nguyen-Ba-Charvet KT, Forcet C, Moyse E, Chetodal, A, Mehlen P (2000) Netrin-1-mediated axon outgrowth and cAMP production requires interaction with adenosine A2B receptor. Nature 407:747–750PubMedCrossRefGoogle Scholar
  60. Corsi C, Melani A, Bianchi L, Pepeu G, Pedata F (1999a) Striatal A2A adenosine receptors differentially regulate spontaneous and K + -evoked glutamate release in vivo in young and aged rats. Neuroreport 10:687–691PubMedGoogle Scholar
  61. Corsi C, Melani A, Bianchi L, Pepeu G, Pedata F (1999b) Effect of adenosine A2A stimulation on GABA release from the striatum of young and aged rats in vivo. Neuroreport 10:3933–3937PubMedGoogle Scholar
  62. 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
  63. Coyle JT, Schwarcz R (1976) Lesion of striatal neurones with kainic acid provides a model for Huntington’s chorea. Nature 263:244–246PubMedCrossRefGoogle Scholar
  64. Cronstein BN (1994) Adenosine, an endogenous anti-inflammatory agent. J Appl Physiol 76:5–13PubMedGoogle Scholar
  65. Cronstein BN, Rosenstein ED, Kramer SB, Weissmann G, Hirschhorn R (1985) Adenosine: a physiologic modulator of superoxide anion generation by human neutrophils. Adenosine acts via an A2 receptor on human neutrophils. J Immunol 135:1366–1371PubMedGoogle Scholar
  66. Cronstein BN, Kubersky SM, Weissmann G, Hirschhorn R (1987) Engagement of adenosine receptors inhibits hydrogen peroxide-release by activated human neutrophils. Clin Immunol Immunopathol 42:76–85PubMedCrossRefGoogle Scholar
  67. Cronstein BN, Daguma L, Nichols D, Hutchison AJ, Williams M (1990) The adenosine/neutrophil paradox resolved: human neutrophils possess both A1 and A2 receptors that both promote chemotaxis and inhibit O2 generation respectively. J Clin Invest 85:1150–1157PubMedCrossRefGoogle Scholar
  68. Cronstein BN, Levin RI, Philips M, Hirschhorn R, Abramson SB, Weissmann G (1992) Neutrophil adherence to endothelium is enhanced via adenosine A1 receptors and inhibited via adenosine A2 receptors. J Immunol 148:2201–2206PubMedGoogle Scholar
  69. Cunha RA, Johansson B, van der Ploeg I, Sebastião AM, Ribeiro JA, Fredholm BB (1994) Evidence for functionally important adenosine A2a receptors in the rat hippocampus. Brain Res 649:208–216PubMedCrossRefGoogle Scholar
  70. Cunha RA, Constantino MC, Sebastião AM, Ribeiro JA (1995) Modification of A1 and A2a adenosine receptor binding in aged striatum, hippocampus and cortex of the rat. Neuroreport 6:1583–1588PubMedCrossRefGoogle Scholar
  71. Cunha RA, Johansson B, Constantino MD, Sebastião AM, Fredholm BB (1996) Evidence for high affinity binding sites for the adenosine A2A receptor agonist [3H]CGS21680 in the rat hippocampus and cerebral cortex that are different from striatal A2A receptors. Naunyn–Schmiedeberg’s Arch Pharmacol 353:261–271CrossRefGoogle Scholar
  72. D’Alimonte I, Ballerini P, Nargi E, Buccella S, Giuliani P, Di Iorio P, Caciagli, F (2007) Staurosporine-induced apoptosis in astrocytes is prevented by A(1) adenosine receptor activation. Neurosci Lett 418:66–71PubMedCrossRefGoogle Scholar
  73. Dall’lgna OP, Porciuncula LO, Souza DO, Cunha RA, Lara DR (2003) Neuroprotection by caffeine and adenosine A(2A) receptor blockade of β-amyloid neurotoxicity. Br J Pharmacol 138: 1207–1209PubMedCrossRefGoogle Scholar
  74. Dall’Igna OP, Fett P, Gomes MW, Souza DO, Cunha RA, Lara DR (2007) Caffeine and adenosine A(2a) receptor antagonists prevent β-amyloid (25–35)-induced cognitive deficits in mice. Exp Neurol 203:241–245PubMedCrossRefGoogle Scholar
  75. Deckert J, Abel F, Kunig G, Hartmann J, Senitz D, Maier H, Ransmayr G, Riederer P (1998) Loss of human hippocampal adenosine A(1) receptors in dementia: evidence for lack of specificity. Neurosci Lett 244:1–4PubMedCrossRefGoogle Scholar
  76. De Mendonca A, Sebastiao AM, Ribeiro JA (1995) Inhibition of NMDA receptor-mediated currents in isolated rat hippocampal-neurons by adenosine A(1) receptor activation. Neuroreport 6:1097–1100PubMedCrossRefGoogle Scholar
  77. Dianzani C, Brunelleschi S, Viano I, Fantozzi R (1994) Adenosine modulation of primed human neutrophils. Eur J Pharmacol 263:223–226PubMedCrossRefGoogle Scholar
  78. Di-Capua N, Sperling O, Zoref-Shani E (2003) Protein kinase C-epsilon is involved in the adenosine-activated signal transduction pathway conferring protection against ischemia-reperffision injury in primary rat neuronal cultures. J Neurochem 84:409–412PubMedCrossRefGoogle Scholar
  79. 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
  80. Dixon AK, Gubitz AK, Sirinathsinghji DJ, Richardson PJ, Freeman TC (1996) Tissue distribution of adenosine receptor mRNAs in the rat. Br J Pharmacol 118:1461–1468PubMedGoogle Scholar
  81. Dixon AK, Widdowson L, Richardson PJ (1997) Desensitisation of the adenosine A1 receptor by the A2A receptor in the rat striatum. J Neurochem 69:315–321PubMedCrossRefGoogle Scholar
  82. Dolphin AC, Prestwich SA (1985) Pertussis toxin reverses adenosine inhibition of neuronal glutamate release. Nature 316:148–150PubMedCrossRefGoogle Scholar
  83. Domenici MR, Scattoni ML, Martire A, Lastoria G, Potenza RL, Borioni A, Venerosi A, Calamandrei G, Popoli P (2007) Behavioral and electrophysiological effects of the adenosine A2A receptor antagonist SCH58261 in R6/2 Huntington’s disease mice. Neurobiol Disease 28:197–205CrossRefGoogle Scholar
  84. 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
  85. Evans MC, Swan JH, Meldrum BS (1987) An adenosine analog, 2-chloroadenosine, protects against long-term development of ischemic cell loss in the rat hippocampus. Neurosci Lett 83:287–292PubMedCrossRefGoogle Scholar
  86. Ezeamuzie CI, Philips E (1999) Adenosine A3 receptors on human eosinophils mediate inhibition of degranulation and superoxide anion release. Br J Pharmacol 127:188–194PubMedCrossRefGoogle Scholar
  87. Fastbom J, Fredholm BB (1985) Inhibition of (3H)glutamate release from rat hippocampal slices by L-PIA. Acta Physiol Scand 125:121–123PubMedCrossRefGoogle Scholar
  88. Fastbom J, Pazos A, Probst A, Palacios JM (1986) Adenosine A1-receptors in human brain: characterisation and autoradiographic visualisation. Neurosci Lett 65:127–132PubMedCrossRefGoogle Scholar
  89. Fastbom J, Pazos A, Palacios JM (1987a) The distribution of adenosine A1 receptors and 5′-nucleotidase in the brain of some commonly used experimental animals. Neuroscience 22:813–826PubMedCrossRefGoogle Scholar
  90. Fastbom J, Pazos A, Probst A, Palacios JM (1987b) Adenosine A1 receptors in the human brain: a quantitative autoradiographic study. Neuroscience 22:827–839PubMedCrossRefGoogle Scholar
  91. Fedorova IM, Jacobson MA, Basile A, Jacobson KA (2003) Behavioral characterization of mice lacking the A(3) adenosine receptor: sensitivity to hypoxic neurodegeneration. Cell Mol Neurobiol 23:431–447PubMedCrossRefGoogle Scholar
  92. Ferkany JW, Zaczek R, Coyle JT (1982) Kainic acid stimulates excitatory amino acid neurotransmitter release at presynaptic receptors. Nature 298:757–759PubMedCrossRefGoogle Scholar
  93. Ferrante RJ, Kowall NW, Cipolloni PB, Storey E, Beal MF (1993) Excitotoxin lesions in primates as a model for Huntington’s disease: histopathologic and neurochemical characterization. Exp Neurol 119:46–71PubMedCrossRefGoogle Scholar
  94. Ferré S, von Euler G, Johansson B, Fredholm BB, Fuxe K (1991) Stimulation of high-affinity adenosine A2 receptors decreases the affinity of dopamine D2 receptors in rat striatal membranes. Proc Natl Acad Sci U S A 88:7238–7241PubMedCrossRefGoogle Scholar
  95. Fiebich BL, Biber K, Gyufko K, Berger R, Bauer J, vanCalker D (1996a) Adenosine A(2b) receptors mediate an increase in interleukin (IL)-6 mRNA and IL-6 protein synthesis in human astroglioma cells. J Neurochem 66:1426–1431PubMedCrossRefGoogle Scholar
  96. Fiebich BL, Biber K, Lieb K, vanCalker D, Berger M, Bauer J, GebickeHaerter PJ (1996b) Cyclooxygenase-2 expression in rat microglia is induced by adenosine A(2a)-receptors. Glia 18:152–160PubMedCrossRefGoogle Scholar
  97. Fiebich BL, Akundi RS, Biber K, Hamke M, Schmidt C, Butcher RD, van Calker D, Willmroth F (2005) IL-6 expression induced by adenosine A(2b) receptor stimulation in U373MG cells depends on p38 mitogen activated kinase and protein kinase C. Neurochem Intern 46:501–512CrossRefGoogle Scholar
  98. Fink JS, Kalda A, Ryu H, Stack EC, Schwarzschild MA, Chen JF, Ferrante RJ (2004) Genetic and pharmacological inactivation of the adenosine A(2A) receptor attenuates 3-nitropropionic acid-induced striatal damage. J Neurochem 88:538–544PubMedCrossRefGoogle Scholar
  99. Finn SF, Swartz KJ, Beal MF (1991) 2-Chloroadenosine attenuates NMDA, kainate and quisqualate toxicity. Neurosci Lett 126:191–194PubMedCrossRefGoogle Scholar
  100. Fotheringham J, Mayne M, Holden C, Nath A, Geiger JD (2004) Adenosine receptors control HIV-1 Tat-induced inflammatory responses through protein phosphatase. Virology 327:186–195PubMedCrossRefGoogle Scholar
  101. Fredholm BB, Dunwiddie TV (1988) How does adenosine inhibit transmitter release? Trends Pharmacol Sci 9:130–134PubMedCrossRefGoogle Scholar
  102. Fredholm BB, Johansson B, Lindstrom K, Wahlstrom G (1998) Age-dependent changes in adenosine receptors are not modified by life-long intermittent alcohol administration. Brain Res 791:177–185PubMedCrossRefGoogle Scholar
  103. Gao Y, Phillis JW (1994) CGS 15943, an adenosine A2 receptor antagonist, reduces cerebral ischemic injury in the Mongolian gerbil. Life Sci 55:PL61–PL65PubMedCrossRefGoogle Scholar
  104. Gerevich Z, Wirkner K, Illes P (2002) Adenosine A(2A) receptors inhibit the N-methyl-D-aspartate component of excitatory synaptic currents in rat striatal neurons. Eur J Pharmacol 451:161–164PubMedCrossRefGoogle Scholar
  105. Gianfriddo M, Melani A, Turchi D, Giovannini MG, Pedata F (2004) Adenosine and glutamate extracellular concentrations and mitogen-activated protein kinases in the striatum of Huntington transgenic mice. Selective antagonism of adenosine A(2A) receptors reduces transmitter outflow. Neurobiol Dis 17:77–88PubMedCrossRefGoogle Scholar
  106. Giménez-Llort L, Fernández-Teruel A, Escorihuela RM, Fredholm BB, Tobeña A, Pekny M, Johansson B (2002) Mice lacking the adenosine A1 receptor are anxious and aggressive, but are normal learners with reduced muscle strength and survival rate. Eur J Neurosci 16:547–550PubMedCrossRefGoogle Scholar
  107. Goncalves ML, Cunha RA, Ribeiro JA (1997) Adenosine A2A receptors facilitate 45Ca2 + uptake through class A calcium channels in rat hippocampal CA3 but not CA1 synaptosomes. Neurosci Lett 238:73–77PubMedCrossRefGoogle Scholar
  108. Goodman RR, Snyder SH (1982) Autoradiographic localisation of adenosine receptors in rat brain using [3H]cyclohexyladenosine. J Neurosci 2:1230–1241PubMedGoogle Scholar
  109. Graham SH, Chen J, Sharp FR, Simon RP (1993) Limiting ischaemic injury by inhibition of excitatory amino acid release. J Cereb Blood Flow Metab 13:88–97PubMedGoogle Scholar
  110. Grisham MB, Hernandez LA, Granger DN (1989) Adenosine inhibits ischemia-reperfusion-induced leukocyte adherence and extravasation. Am J Physiol 257:H1334–H1339PubMedGoogle Scholar
  111. Grondin R, Bédard PJ, Hadj Tahar A, Grégoire L, Mori A, Kase H (1999) Antiparkinsonian effect of a new selective adenosine A2A receptor antagonist in MPTP-treated monkeys. Neurology 52:1673–1677PubMedGoogle Scholar
  112. Guidetti P, Luthi-Carter RE, Augood SJ, Schwarcz R (2004) Neostriatal and cortical quinolinate levels are increased in early grade Huntington’s disease. Neurobiol Dis 17:455–461PubMedCrossRefGoogle Scholar
  113. Hannon JP, Bray-French KM, Phillips RM, Fozard JR (1998) Further pharmacological characterization of the adenosine receptor subtype mediating inhibition of oxidative burst in human isolated neutrophils. Drug Dev Res 43:214–224CrossRefGoogle Scholar
  114. Hara H, Onodera H, Kato H, Kogure K (1992) Effects of aging on signal transmission and transduction systems in the gerbil brain: morphological and autoradiographic study. Neuroscience 46:475–488PubMedCrossRefGoogle Scholar
  115. Haskó G, Cronstein BN (2004) Adenosine: an endogenous regulator of innate immunity. Trends Immunol 25(1):33–39PubMedCrossRefGoogle Scholar
  116. Haskó G, Németh ZH, Vizi ES, Salzman AL, Szabó C (1998) An agonist of adenosine A3 receptors decreases interleukin-12 and interferon-gamma production and prevents lethality in endotoxemic mice. Eur J Pharmacol 358:261–268PubMedCrossRefGoogle Scholar
  117. Haskó G, Pacher P, Deitch EA, Vizi ES (2007) Shaping of monocyte and macrophage function by adenosine receptors. Pharmacol Ther 113:264–275PubMedCrossRefGoogle Scholar
  118. Hauber W, Bareiss A (2001) Facilitative effects of an adenosine A1∕A2 receptor blockade on spatial memory performance of rats: selective enhancement of reference memory retention during the light period. Behav Brain Res 118(1):43–52PubMedCrossRefGoogle Scholar
  119. Heese K, Fiebich BL, Bauer J, Otten U (1997) Nerve growth factor (NGF) expression in rat microglia is induced by adenosine A(2a)-receptors. Neurosci Lett 231:83–86PubMedCrossRefGoogle Scholar
  120. Héron A, Lasbennes F, Seylez J (1993) Adenosine modulation of amino acid release in rat hippocampus during ischaemia and veratridine depolarisation. Brain Res 608:27–32PubMedCrossRefGoogle Scholar
  121. Héron 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, behavioural and histological consequences of ischaemia. Brain Res 641:217–224PubMedCrossRefGoogle Scholar
  122. Hiraide T, Katsura K, Muramatsu H, Asano G, Katayama Y (2001) Adenosine receptor antagonists cancelled the ischemic tolerance phenomenon in gerbil. Brain Res 910:94–98PubMedCrossRefGoogle Scholar
  123. Hollins C, Stone TW (1980) Adenosine inhibition of GABA release from slices of rat cerebral cortex. Br J Pharmacol 69:107–112PubMedGoogle Scholar
  124. Hooper N, Fraser C, Stone TW (1996) Effects of purine analogues on spontaneous alternation in mice. Psychopharmacology 123(3):250–257PubMedCrossRefGoogle Scholar
  125. Hosseinzadeh H, Stone TW (1998) Tolbutamide blocks postsynaptic but not presynaptic effects of adenosine on hippocampal CA1 neurons. J Neural Transm 105:161–172PubMedCrossRefGoogle Scholar
  126. Huang QY, Wei C, Yu LQ, Coelho JE, Shen HY, Kalda A, Linden J, Chen JF (2006) Adenosine A2A receptors in bone marrow-derived cells but not in forebrain neurons are important contributors to 3-nitropropionic acid-induced striatal damage as revealed by cell-type-selective inactivation. J Neurosci 26:11371–11378PubMedCrossRefGoogle Scholar
  127. Hutchison AJ, Webb RL, Oei HH, Ghai GR, Zimmerman MB, Williams M (1989) CGS21680, an A2 selective adenosine receptor agonist with preferential hypotensive activity. J Pharmacol Exp Ther 251:47–55PubMedGoogle Scholar
  128. Ikeda M, Mackay KB, Dewar D, Mcculloch J (1993) Differential alterations in adenosine-A(1) and kappa-1-opioid receptors in the striatum in Alzheimer’s-disease. Brain Res 616:211–217PubMedCrossRefGoogle Scholar
  129. Jaarsma D, Sebens JB, Korf J (1991) Reduction of adenosine-A1-receptors in the perforant pathway terminal zone in Alzheimer hippocampus. Neurosci Lett 121:111–114PubMedCrossRefGoogle Scholar
  130. Jacobson KA (1998) Adenosine A3 receptors: novel ligands and paradoxical effects. Trends Pharmacol Sci 19:184–191PubMedCrossRefGoogle Scholar
  131. Jacobson I, Hamberger A (1985) Kainic acid-induced changes of extracellular amino acid levels, evoked potentials and EEG activity in the rabbit olfactory bulb. Brain Res 348:289–296PubMedCrossRefGoogle Scholar
  132. Jansen KLR, Faull RLM, Dragunow M, Synek BL (1990) Alzheimer’s disease: changes in hippocampal N-methyl-D-aspartate, quisqualate, neurotensin, adenosine, benzodiazepine, serotonin and opioid receptors—an autoradiographic study. Neuroscience 39:613–627PubMedCrossRefGoogle Scholar
  133. Jarvis MF, Williams M (1989) Direct autoradiographic localisation of adenosine A2 receptors in the brain using the A2-selective agonist, [3H]CGS21680. Eur J Pharmacol 168:243–246PubMedCrossRefGoogle Scholar
  134. 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
  135. Johnson-Kozlow M, Kritz-Silverstein D, Barrett-Connor E, Morton D (2002) Coffee consumption and cognitive function among older adults. Am J Epidemiol 156:842–850PubMedCrossRefGoogle Scholar
  136. Johnston JB, Silva C, Gonzalez G, Holden J, Warren KG, Metz LM, Power C (2001) Diminished adenosine A1 receptor expression on macrophages in brain and blood of patients with multiple sclerosis. Ann Neurol 49:650–658PubMedCrossRefGoogle Scholar
  137. Jones PA, Smith RA, Stone TW (1998a) Protection against intrahippocampal kainate excitotoxicity by intracerebral administration of an adenosine A2A receptor antagonist. Brain Res 800: 328–335PubMedCrossRefGoogle Scholar
  138. Jones PA, Smith RA, Stone TW (1998b) Protection against kainate-induced excitotoxicity by adenosine A2A receptor agonists and antagonists. Neuroscience 85:229–237PubMedCrossRefGoogle Scholar
  139. Kalaria RN, Sromek S, Wilcox BJ, Unnerstall JR (1990) Hippocampal adenosine-A1-receptors are decreased in Alzheimer’s-disease. Neurosci Lett 118:257–260PubMedCrossRefGoogle Scholar
  140. Kanda T, Jackson MJ, Smith LA, Pearce RK, Nakamura J, Kase H, Kuwana Y, Jenner P (1998) Adenosine A2A antagonist: a novel antiparkinsonian agent that does not provoke dyskinesia in parkinsonian monkeys. Ann Neurol 43:507–513PubMedCrossRefGoogle Scholar
  141. Kano T, Katayama Y, Kawamata T, Hirota H, Tsubokawa T (1994) Propentofylline administered by microdialysis attenuates ischaemia-induced hippocampal damage but not excitatory amino acid release in gerbils. Brain Res 641:149–154PubMedCrossRefGoogle Scholar
  142. Khaspekov L, Shamloo M, Victorov I, Wieloch T (1998) Sublethal in vitro glucose-oxygen deprivation protects cultured hippocampal neurons against a subsequent severe insult. Neuroreport 9:1273–1276PubMedCrossRefGoogle Scholar
  143. Knutsen LJS, Sheardown MJ, Roberts SM, Mogensen JP, Olsen UB, Thomsen C, Bowler AN (1998) Adenosine A1 and A3 selective N-alkoxypurines as novel cytokine modulators and neuroprotectants. Drug Dev Res 45:214–221CrossRefGoogle Scholar
  144. Kohler C, Schwarcz R, Fuxe K (1978) Perforant path transections protect hippocampal granule cells from kainate lesion. Neurosci Lett 10:241–246PubMedCrossRefGoogle Scholar
  145. Kopf SR, Melani A, Pedata F, Pepeu G (1999) Adenosine and memory storage: effect of A(1) and A(2) receptor antagonists. Psychopharmacology 146:214–219PubMedCrossRefGoogle Scholar
  146. Kreckler LM, Wan TC, Ge ZD, Auchampach JA (2006) Adenosine inhibits tumor necrosis factor-alpha release from mouse peritoneal macrophages via A(2A) and A(2B) but not the A(3) adenosine receptor. J Pharmacol Exp Ther 317:172–180PubMedCrossRefGoogle Scholar
  147. Kurokawa M, Kirk IP, Kirkpatrick KA, Kase H, Richardson PJ (1994) Inhibition by KF17837 of adenosine A2A receptor-mediated modulation of striatal GABA and acetylcholine release. Br J Pharmacol 113:43–48PubMedGoogle Scholar
  148. Lai DM, Tu YK, Liu IM, Cheng JT (2005) Increase of adenosine A1 receptor gene expression in cerebral ischemia of Wistar rats. Neurosci Lett 387:59–61PubMedCrossRefGoogle Scholar
  149. Lappin D, Whaley K (1984) Adenosine A2 receptors on human monocytes modulate C2 production. Clin Exp Immunol 57:454–460PubMedGoogle Scholar
  150. Latini S, Pazzagli M, Pepeu G, Pedata F (1996) A2 adenosine receptors: their presence and neuromodulatory role in the CNS. Gen Pharmacol 27:925–933PubMedGoogle Scholar
  151. Latini S, Bordoni F, Corradetti R, Pepeu G, Pedata F (1999) 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
  152. Lau Y-S, Mouradian MM (1993) Protection against acute MPT-induced dopamine depletion in mice by adenosine. J Neurochem 60:768–771PubMedCrossRefGoogle Scholar
  153. Lee FS, Chao MV (2001) Activation of Trk neurotrophin receptors in the absence of neurotrophins. Proc Natl Acad Sci USA 98:3555–3560PubMedCrossRefGoogle Scholar
  154. Lee KS, Reddington M (1986) Autoradiographic evidence for multiple CNS binding sites for adenosine derivative. Neuroscience 19:535–549PubMedCrossRefGoogle Scholar
  155. Lehmann A, Isacsson H, Hamberger A (1983) Effects of in vivo administration of kainic acid on the extracellular amino acid pool in the rabbit hippocampus. J Neurochem 40:1314–1320PubMedGoogle Scholar
  156. LeVraux V, Chen YL, Masson I, De Sousa M, Giroud JP, Florentin I, Chauvelot-Moachon L (1993) Inhibition of human monocyte TNF production by adenosine receptor agonists. Life Sci 52:1917–1924CrossRefGoogle Scholar
  157. Li XX, Nomura T, Aihara H, Nishizaki T (2001) Adenosine enhances glial glutamate efflux via A2A adenosine receptors. Life Sci 68:1343–1350PubMedCrossRefGoogle Scholar
  158. Linden J, Thai T, Figler H, Jin X, Robeva AS (1999) Characterization of human A2B adenosine receptors: radioligand binding, western blotting, and coupling to Gq in human embryonic kidney 293 cells and HMC-1 mast cells. Mol Pharmacol 56:705–713PubMedGoogle Scholar
  159. Link AA, Kino T, Worth JA, McGuire JL, Crane ML, Chrousos GP, Wilder RL, Elenkov IJ (2000) Ligand activation of the adenosine A2A receptors inhibits IL-12 production by human monocytes. J Immunol 164:436–442PubMedGoogle Scholar
  160. Lipton SA, Rosenberg PA (1994) Excitatory amino acids as a final common pathway for neurologic disorders. N Engl J Med 330:613–622PubMedCrossRefGoogle Scholar
  161. Liu HC, Hon CJ, Liu TY, Tsai, SJ (2005) Association analysis of adenosine A2a receptor 1976T > C polymorphisms and Alzheimer’s disease. Eur Neurol 53:99–100PubMedCrossRefGoogle Scholar
  162. Liu YH, Xiong L, Chen SY, Wang Q (2006) Isoflurane tolerance against focal cerebral ischemia is attenuated by adenosine A(1) receptor antagonists. Can J Anaes 53:194–201CrossRefGoogle Scholar
  163. Lozza G, Conti A, Ongini E, Monopoli A (1997) Cardioprotective effects of adenosine A1 and A2A receptor agonists in the isolated heart. Pharmacol Res 35:57–64PubMedCrossRefGoogle Scholar
  164. MacGregor DG, Stone TW (1993) Inhibition by the adenosine analogue, (R)-N 6-phenylisopropyladenosine, of kainic acid neurotoxicity in rat hippocampus after systemic administration. Br J Pharmacol 109:316–321PubMedGoogle Scholar
  165. MacGregor DG, Miller WJ, Stone TW (1993) Mediation of the neuroprotective action of R-phenylisopropyladenosine through a centrally located adenosine A1 receptor. Br J Pharmacol 110:470–476PubMedGoogle Scholar
  166. MacGregor DG, Jones PA, Maxwell WL, Graham DI, Stone TW (1996) Prevention by a purine analogue of kainate-induced neuropathology in rat hippocampus. Brain Res 725:115–120PubMedGoogle Scholar
  167. Maemoto T, Tada M, Mihara T, Ueyama N, Matsuoka H, Harada K, Yamaji T, Shirakawa K, Kuroda S, Akahane A, Iwashita A, Matsuoka N, Mutoh S (2004) Pharmacological characterization of FR194921, a new potent, selective, and orally active antagonist for central adenosine A(1) receptors. J Pharmacol Sci 96:42–52PubMedCrossRefGoogle Scholar
  168. Mager R, Ferroni S, Schubert P (1990) Adenosine modulates a voltage-dependent chloride conductance in cultured hippocampal neurons. Brain Res 532:58–62PubMedCrossRefGoogle Scholar
  169. Maggirwar SB, Dhanraj DN, Somani SM, Ramkumar V (1994) Adenosine acts as an endogenous activator of the cellular antioxidant defense system. Biochem Biophys Res Commun 201: 508–515PubMedCrossRefGoogle Scholar
  170. Maglione V, Giallonardo P, Cannella M, Martino T, Frati L, Squitieri F (2005) Adenosine A(2A) receptor dysfunction correlates with age at onset anticipation in blood platelets of subjects with Huntington’s disease. Am J Med Genet B Neuropsychiatr Genet 139B:101–105PubMedCrossRefGoogle Scholar
  171. Maglione V, Cannella M, Martino T, De Blasi A, Frati L, Squitieri F (2006) The platelet maximum number of A2A-receptor binding sites (Bmax) linearly correlates with age at onset and CAG repeat expansion in Huntington’s disease patients with predominant chorea. Neurosci Lett 393:27–30PubMedCrossRefGoogle Scholar
  172. Maia L, de Mendonça A (2002) Does caffeine intake protect from Alzheimer’s disease? Eur J Neurol 9:377–382PubMedCrossRefGoogle Scholar
  173. Mally J, Stone TW (1994) The effect of theophylline on parkinsonian symptoms. J Pharm Pharmacol 46:515–517PubMedGoogle Scholar
  174. Mally J, Stone TW (1996) Potential role of adenosine antagonist therapy in pathological tremor disorders. Pharmacol Ther 72:243–250PubMedCrossRefGoogle Scholar
  175. Mally J, Stone TW (1998) Potential of adenosine A(2A) receptor antagonists in the treatment of movement disorders. CNS Drugs 10:311–320CrossRefGoogle Scholar
  176. Mangiarini L, Sathasivam K, Seller M, Cozens B, Harper A, Hetherington C, Lawton M, Trottier T, Lehrach H, Davies SW, Bates GP (1996) Exon 1 of the HD gene with an expanded CAG repeat is sufficient to cause a progressive neurological phenotype in transgenic mice. Cell 87:493–506PubMedCrossRefGoogle Scholar
  177. Martinez-Mir MI, Probst A, Palacios JM (1991) Adenosine A2 receptors: selective localisation in the human basal ganglia and alterations with disease. Neuroscience 42:697–706PubMedCrossRefGoogle Scholar
  178. Matherne GP, Linden J, Byford AM, Gauthier NS, Headrick JP (1997) Transgenic A1 adenosine receptor overexpression increases myocardial resistance to ischaemia. Proc Nat Acad Sci USA 94:6541–6546PubMedCrossRefGoogle Scholar
  179. Mayfield RD, Suzuki F, Zahniser NR (1993) Adenosine A2A receptor modulation of electrically evoked endogenous GABA release from rat globus pallidus. J Neurochem 60:2334–2337PubMedCrossRefGoogle Scholar
  180. Mayne M, Shepel PN, Jiang Y, Geiger JD, Power C (1999) Dysregulation of adenosine A(1) receptor-mediated cytokine expression in peripheral blood mononuclear cells from multiple sclerosis patients. Ann Neurol 45:633–639PubMedCrossRefGoogle Scholar
  181. McLarnon JG, Choi HB, Lue LF, Walker DG, Kim SU (2005) Perturbations in calcium-mediated signal transduction in microglia from Alzheimer’s disease patients. J Neurosci Res 81:426–435PubMedCrossRefGoogle Scholar
  182. McRae A, Rudolphi KA, Schubert P (1994) Propentofylline depresses amyloid and Alzheimer’s CSF microglial antigens after ischaemia. Neuroreport 5:1193–1196PubMedGoogle Scholar
  183. McWhinney CD, Dudley MW, Bowlin TL, Peet NP, Schook L, Bradshaw M, De M, Borcherding DR, Edwards CK 3rd (1996) Activation of adenosine A3 receptors on macrophages inhibits TNFα. Eur J Pharmacol 310:209–216PubMedCrossRefGoogle Scholar
  184. Meerlo P, Roman V, Farkas E, Keijser JN, Nyakas C, Luiten PGM (2004) Ageing-related decline in adenosine A1 receptor binding in the rat brain: an autoradiographic study. J Neurosci Res 78:742–748PubMedCrossRefGoogle Scholar
  185. Meiners I, Hauschildt S, Nieber K, Munch G (2004) Pentoxyphylline and propentophylline are inhibitors of TNF-ot release in monocytes activated by advanced glycation endproducts. J Neural Transm 111:441–447PubMedCrossRefGoogle Scholar
  186. Melani A, Pantoni L, Corsi C, Bianchi L, Monopoli A, Bertorelli R, Pepeu G, Pedata F (1999) Striatal outflow of adenosine, excitatory amino acids, GABA, and taurine in awake, freely moving rats after middle cerebral artery occlusion: correlation with neurological deficit and histopathological damage. Stroke 30:2448–2454PubMedGoogle Scholar
  187. Meldrum DR, Cain BS, Cleveland JC Jr, Meng X, Ayala A, Banerjee A, Harken AH (1997) Adenosine decreases post-ischemic cardiac TNF-α production: anti-inflammatory implications for preconditioning and transplantation. Immunology 92:472–477PubMedCrossRefGoogle Scholar
  188. Merkel LA, Lappe RW, Rivera LM, Cox BF, Perrone MH (1992) Demonstration of vasorelaxant activity with an A1-selective adenosine agonist in porcine coronary artery: involvement of potassium channels. J Pharmacol Exp Ther 260:437–443PubMedGoogle Scholar
  189. Michaelis ML, Michaelis EK, Myers SL (1979) Adenosine modulation of synaptosomal dopamine release. Life Sci 24:2083–2092PubMedCrossRefGoogle Scholar
  190. Mielke R, Kessler J, Szelies B, Herholz K, Wienhard K, Heiss WD (1996a) Vascular dementia: perfusional and metabolic disturbances and effects of therapy. J Neural Transm 47:183–191Google Scholar
  191. Mielke R, Kittner B, Ghaemi M, Kessler J, Szelies B, Herholz K, Heiss WD (1996b) Propentofylline improves regional cerebral glucose metabolism and neuropsychologic performance in vascular dementia. J Neurol Sci 141:59–64PubMedCrossRefGoogle Scholar
  192. Miller WJ, Macgregor DG, Stone TW (1994) Time-course of purine protection against kainate-induced increase in hippocampal [H-3] PK11195 binding. Brain Res Bull 34:133–136PubMedCrossRefGoogle Scholar
  193. Monopoli A, Lozza G, Forlani A, Mattavelli A, Ongini E (1998) Blockade of adenosine A2A receptors by SCH58261 results in neuroprotective effects in cerebral ischaemia in rats. Neuroreport 9:3955–3959PubMedCrossRefGoogle Scholar
  194. Moreau JL, Huber G (1999) Central adenosine A2A receptors: an overview. Brain Res Rev 31: 65–82PubMedCrossRefGoogle Scholar
  195. Moreno MB, Hevia H, Santamaria M, Sepulcre J, Munoz J, Garcia-Trevijano ER, Berasain C, Corrales FJ, Avila MA, Villoslada P (2006) Methylthioadenosine reverses brain autoimmune disease. Ann Neurol 60:323–334PubMedCrossRefGoogle Scholar
  196. Muller CE (1997) A(1)-adenosine receptor antagonists. Exp Opin Ther Pat 7:419–440CrossRefGoogle Scholar
  197. Muller CE (2000) A(2A) adenosine receptor antagonists—future drugs for Parkinson’s disease? Drugs Future 25:1043–1052CrossRefGoogle Scholar
  198. Murray TF (1982) Up-regulation of rat cortical adenosine receptors following chronic administration of theophylline. Eur J Pharmacol 82:113–114PubMedCrossRefGoogle Scholar
  199. Nakamura M, Nakakimura K, Matsumoto M, Sakabe T (2002) Rapid tolerance to focal cerebral ischemia in rats is attenuated by adenosine A(1) receptor antagonist. J Cereb Blood Flow Metab 22:161–170PubMedCrossRefGoogle Scholar
  200. Nakata H, Yoshioka K, Saitoh O (2003) Hetero-oligomerization between adenosine A1 and P2Y1 receptors in living cells: formation of ATP-sensitive adenosine receptors. Drug Dev Res 58:340–349CrossRefGoogle Scholar
  201. Nikbakht M-R, Stone TW (2001) Activation of NMDA receptors suppresses the presynaptic effects of adenosine. Br J Pharmacol 133:155PGoogle Scholar
  202. Nishizaki T (2004) ATP- and adenosine-mediated signaling in the central nervous system: adenosine stimulates glutamate release from astrocytes via A2A adenosine receptors J Pharmacol Sci 94:100–102Google Scholar
  203. 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 A(2a) adenosine receptors. Glia 39:133–47PubMedCrossRefGoogle Scholar
  204. Noble S, Wagstaff AJ (1997) Propentofylline. CNS Drugs 8:257–264CrossRefGoogle Scholar
  205. Norenberg W, Wirkner K, Illes P (1997) Effect of adenosine and some of its structural analogues on the conductance of NMDA receptor channels in a subset of rat neostriatal neurones. Br J Pharmacol 122:71–80PubMedCrossRefGoogle Scholar
  206. Norenberg W, Wirkner K, Assmann H, Richter M, Illes P (1998) Adenosine A(2A) receptors inhibit the conductance of NMDA receptor channels in rat neostriatal neurons. Aminoacids 14:33–39Google Scholar
  207. Normile HJ, Barraco RA (1991) N 6-Cyclopentyladenosine impairs passive avoidance retention by selective action at A1 receptors. Brain Res Bull 27:101–104PubMedCrossRefGoogle Scholar
  208. O’Kane EM, Stone TW (1998) Interactions between A1 and A2 adenosine receptor-mediated responses in the rat hippocampus in vitro. Eur J Pharmacol 362:17–25PubMedCrossRefGoogle Scholar
  209. O’Regan MH, Simpson RE, Perkins LM, Phillis JW (1992) The selective A2 adenosine receptor agonist CGS21680 enhances excitatory amino acid release from the ischaemic rat cerebral cortex. Neurosci Lett 138:169–172PubMedCrossRefGoogle Scholar
  210. Ochiishi T, Chen L, Yukawa A, Saitoh Y, Sekino Y, Arai T, Nakata H, Miyamoto H (1999a) Cellular localisation of adenosine A1 receptors in rat forebrain: immunohistochemical analysis using adenosine A1 receptor-specific monoclonal antibody. J Comp Neurol 411:301–316PubMedCrossRefGoogle Scholar
  211. Ochiishi T, Saitoh Y, Yukawa A, Saji M, Ren Y, Shirao T, Miyamoto H, Nakata H, Sekino Y (1999b) High levels of adenosine A1 receptor-like immunoreactivity in the CA2/CA3a region of the adult rat hippocampus. Neuroscience 93:955–967PubMedCrossRefGoogle Scholar
  212. Ochoa CM, Jackson TA, Aaron CS, Lahti RA, Strain GM, Von Voigtlander PF (1992) Antagonism of kainic acid lesions in the mouse hippocampus by U-54494A and U-50488H. Life Sci 51:1135–1143CrossRefGoogle Scholar
  213. Okazaki MM, Nadler JV (1988) Protective effects of mossy fibre lesions against kainic acid induced seizures and neuronal degeneration. Neuroscience 26:763–781PubMedCrossRefGoogle Scholar
  214. Okonkwo DO, Reece TB, Laurent JJ, Hawkins AS, Ellman PI, Linden J, Kron IL, Tribble CG, Stone JR, Kern JA (2006) A comparison of adenosine A(2A) agonism and methylprednisolone in attenuating neuronal damage and improving functional outcome after experimental traumatic spinal cord injury in rabbits. J Neurosurg 4:64–70Google Scholar
  215. Oliveira JC, Constantino MD, Sebastiao AM, Ribeiro JA (1995) Ascorbate/Fe3 + -induced peroxidation and inhibition of the binding of A1 adenosine receptor ligands in rat-brain membranes. Neurochem Int 26:263–268PubMedCrossRefGoogle Scholar
  216. Ongini E, Fredholm BB (1996) Pharmacology of adenosine A2A receptors. Trends Pharmacol Sci 17:364–372PubMedCrossRefGoogle Scholar
  217. Ongini E, Adami M, Ferri C, Bertorelli R (1997) Adenosine A2A receptors and neuroprotection. Ann NY Acad Sci 825:30–48PubMedCrossRefGoogle Scholar
  218. Ongini E, Monopoli A, Impagnatiello F, Fredduzzi S, Schwarzschild M, Chen JF (2001) Dual actions of A2A adenosine receptor antagonists on motor dysfunction and neurodegenerative processes. Drug Dev Res 52:379–386CrossRefGoogle Scholar
  219. Pagonopoulou O, Angelatou F (1992) Reduction of A1 adenosine receptors in cortex, hippocampus and cerebellum in ageing mouse brain. Neuroreport 3:735–737PubMedCrossRefGoogle Scholar
  220. Palmer TM, Poucher SM, Jacobson KA, Stiles GL (1995) 125I-4-[7-amino-2-{2-furyl} {1,2,4}triazolo{2,3-a} {1,3,5}triazin-5-yl-amino]ethyl)phenol, a high affinity antagonist radioligand selective for the A2A adenosine receptor. Mol Pharmacol 48:970–974PubMedGoogle Scholar
  221. Parkinson FE, Rudolphi KA, Fredholm BB (1994) Propentofylline: a nucleoside transport inhibitor with neuroprotective effects in cerebral ischaemia. Gen Pharmacol 25:1053–1058PubMedGoogle Scholar
  222. Pazzagli M, Corsi C, Latini S, Pedata F, Pepeu G (1994) In vivo regulation of extracellular adenosine levels in the cerebral cortex by NMDA and muscarinic receptors. Eur J Pharmacol 254:277–282PubMedCrossRefGoogle Scholar
  223. 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
  224. Pedata F, Gianfriddo M, Turchi D, Melani A (2005) The protective effect of adenosine A(2A) receptor antagonism in cerebral ischemia. Neurol Res 27:169–174PubMedCrossRefGoogle Scholar
  225. 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
  226. Phillis JW, O’Regan MH (1993) Prevention of ischemic brain injury by adenosine receptor activation. Drug Dev Res 28:390–394CrossRefGoogle Scholar
  227. Pierson PM, Peteri-Brunbäck B, Pisani DF, Abbracchio MP, Mienville JM, Rosso L (2007) A(2b) receptor mediates adenosine inhibition of taurine efflux from pituicytes. Biol Cell 99:445–454PubMedCrossRefGoogle Scholar
  228. Pignataro G, Simon RP, Boison D (2007) Transgenic overexpression of adenosine kinase aggravates cell death in ischemia. J Cereb Blood Flow Metab 27:1–5PubMedCrossRefGoogle Scholar
  229. Pintor A, Galluzzo M, Grieco R, Pèzzola 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
  230. Pitsikas N, Borsini F (1997) The adenosine A1 receptor antagonist BIIP 20 counteracts scopolamine-induced behavioral deficits in the passive avoidance task in the rat. Eur J Pharmacol 328:19–22PubMedCrossRefGoogle Scholar
  231. Poli A, Lucchi R, Vibio M, Barnabei O (1991) Adenosine and glutamate modulate each other’s release from rat hippocampal synaptosomes. J Neurochem 57:298–306PubMedCrossRefGoogle Scholar
  232. Popoli P, Pèzzola A, Domenici MR, Sagratella S, Diana G, Caporali MG, Bronzetti E, Vega J, Scotti de Carolis A (1994) Behavioral and electrophysiological correlates of the quinolinic acid rat model of Huntington’s disease in rats. Brain Res Bull 35:329–335PubMedCrossRefGoogle Scholar
  233. Popoli P, Betto P, Reggio R, Ricciarello G (1995) Adenosine A(2A) receptor stimulation enhances striatal extracellular glutamate levels in rats. Eur J Pharmacol 287:215–217PubMedCrossRefGoogle Scholar
  234. Popoli P, Pintor A, Domenici MR, Frank C, Tebano MT, Pèzzola 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
  235. Popoli P, Blum D, Martire A, Ledent C, Ceruti S, Abbracchio MP (2007) Functions, dysfunctions and possible therapeutic relevance of adenosine A2A receptors in Huntington’s disease. Prog Neurobiol 81:331–348PubMedCrossRefGoogle Scholar
  236. Pousinha PA, Diogenes JM, Ribeiro AJ, Sebastiao AM (2006) Triggering of BDNF facilitatory action on neuromuscular transmission by adenosine A2A receptors. Neurosci Lett 404:143–147PubMedCrossRefGoogle Scholar
  237. Prediger RDS, Batista LC, Takahashi RN (2005) Caffeine reverses age-related deficits in olfactory discrimination and social recognition memory in rats: involvement of adenosine A(1) and A(2A) receptors. Neurobiol Ageing 26:957–964CrossRefGoogle Scholar
  238. Press NJ, Gessi S, Borea PA, Polosa R (2007) Therapeutic potential of adenosine receptor antagonists and agonists. Exp Opin Ther Pat 17:979–991CrossRefGoogle Scholar
  239. Prior C, Torres RJ, Puig JG (2006) Hypoxanthine effect on equilibrative and concentrative adenosine transport in human lymphocytes. Implications in the pathogenesis of Lesch–Nyhan syndrome. Nucleosides Nucleotides Nucl Acids 25:1065–1069CrossRefGoogle Scholar
  240. 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
  241. Pugliese AM, Coppi E, Volpini R, Cristalli G, Corradetti R, Jeong LS, Jacobson KA, Pedata F (2007) Role of adenosine A(3) receptors on CA1 hippocampal transmission during oxygen-glucose deprivation episodes of different duration. Biochem Pharmacol 74:768–779PubMedCrossRefGoogle Scholar
  242. Quintana JLB, Allam MF, Del Castillo AS, Navajas RFC (2007) Alzheimer’s disease and coffee: a review. Neurol Res 29:91–95CrossRefGoogle Scholar
  243. Ramakers BP, Riksen NP, Rongen GA, van der Hoeven JG, Smits P, Pickkers P (2006) The effect of adenosine receptor agonists on cytokine release by human mononuclear cells depends on the specific Toll-like receptor subtype used for stimulation. Cytokine 35:95–99PubMedCrossRefGoogle Scholar
  244. Rathbone MP, Middlemiss PJ, Kim JK, Gysbers JW, Deforge SP, Smith RW, Hughes DW (1992) Adenosine and its nucleotides stimulate proliferation of chick astrocytes and human astrocytoma cells. Neurosci Res 13:1–17PubMedCrossRefGoogle Scholar
  245. Rathbone MP, Middlemiss PJ, Gysbers JW, Andrew C, Herman MAR, Reed JK, Ciccarelli R, Di Iorio P, Caciagli F (1999) Trophic effects of purines in neurons and glial cells. Prog Neurobiol 59:663–690PubMedCrossRefGoogle Scholar
  246. Reece TB, Okonkwo DO, Ellman PI, Warren PS, Smith RL, Hawkins AS, Linden J, Kron IL, Tribble CG, Kern JA (2004) The evolution of ischemic spinal cord injury in function, cytoarchitecture, and inflammation and the effects of adenosine A(2A) receptor activation. J Thorac Cardiovasc Surg 128:925–932PubMedGoogle Scholar
  247. Reece TB, Kron IL, Okonkwo DO, Laurent JJ, Tache-Leon C, Maxey TS, Ellman PI, Linden J, Tribble CG, Kern JA (2006) Functional and cytoarchitectural spinal cord protection by ATL-146e after ischemia/reperfusion is mediated by adenosine receptor agonism. J Vasc Surg 44:392–397PubMedCrossRefGoogle Scholar
  248. Regenold JT, Illes P (1990) Inhibitory adenosine A1-receptors on rat locus coeruleus neurones. An intracellular electrophysiological study. Naunyn–Schmied Arch Pharmacol 341:225–231Google Scholar
  249. Reggio R, Pezzola A, Popoli P (1999) The intrastratial injection of an adenosine A(2) receptor antagonist prevents frontal cortex EEG abnormalities in a rat model of Huntington’s disease. Brain Res 831:315–318PubMedCrossRefGoogle Scholar
  250. Revan S, Montesinos MC, Naime D, Landau S, Cronstein BN (1996) Adenosine A2 receptor occupancy regulates stimulated neutrophil function via activation of a serine/threonine protein phosphatase. J Biol Chem 271:17114–17118PubMedCrossRefGoogle Scholar
  251. Ribeiro JA, Sebastiao AM, de Mendonça A (2002) Adenosine receptors in the nervous system: pathophysiological implications. Prog Neurobiol 68:377–392PubMedCrossRefGoogle Scholar
  252. Riedel W, Hogervorst E, Leboux R, Verhey F, Vanpraag H, Jolles J (1995) Caffeine attenuates scopolamine-induced memory impairment in humans. Psychopharmacology 122:158–168PubMedCrossRefGoogle Scholar
  253. Ritchie PK, Spangelo BL, Krzymowski DK, Rossiter TB, Kurth E, Judd AM (1997) Adenosine increases interleukin-6 release and decreases TNF release from rat adrenal zona glomerulosa cells, ovarian cells, anterior pituitary cells and peritoneal macrophages. Cytokine 9:187–198PubMedCrossRefGoogle Scholar
  254. Rivkees SA, Price SL, Zhou FC (1995) Immunohistochemical detection of A1 adenosine receptors in rat brain with emphasis on localisation in the hippocampal formation, cerebral cortex, cerebellum and basal ganglia. Brain Res 677:193–203PubMedCrossRefGoogle Scholar
  255. Rivkees SA, Thevananther S, Hao H (2000) Are A3 adenosine receptors expressed in the brain? Neuroreport 11:1025–1030PubMedCrossRefGoogle Scholar
  256. Robledo P, Ursu G, Mahy N (1999) Effects of adenosine and gamma-aminobutyric acid A receptor antagonists on N-methyl-D-aspartate induced neurotoxicity in the rat hippocampus. Hippocampus 9:527–533PubMedCrossRefGoogle Scholar
  257. Rodriguez A, Martin M, Albasanz JL, Barrachina M, Espinosa JC, Torres JM, Ferrer I (2006) Adenosine A(1) receptor protein levels and activity is increased in the cerebral cortex in Creutzfeldt–Jakob disease and in bovine spongiform encephalopathy-infected bovine-PrP mice. J Neuropathol Exp Neurol 65:964–975PubMedCrossRefGoogle Scholar
  258. Rosi S, McGann K, Hauss-Wegrzyniak B, Wenk GL (2003) The influence of brain inflammation upon neuronal adenosine A(2B) receptors. J Neurochem 86:220–227PubMedCrossRefGoogle Scholar
  259. Rubaj A, Zgodzinski W, Sieklucka-Dziuba M (2003) The influence of adenosine A3 receptor agonist: IB-MECA, on scopolamine- and MK-801-induced memory impairment. Behav Brain Res 141:11–17PubMedCrossRefGoogle Scholar
  260. Rudolphi KA, Schubert P (1997) Modulation of neuronal and glial cell function by adenosine and neuroprotection in vascular dementia. Behav Brain Res 83:123–128PubMedCrossRefGoogle Scholar
  261. Rudolphi KA, Keil M, Hinze HJ (1987) Effect of theophylline on ischemically induced hippocampal damage in Mongolian gerbils: a behavioural and histopathological study. J Cereb Blood Flow Metab 7:74–81PubMedGoogle Scholar
  262. Rudolphi KA, Keil M, Fastbom J, Fredholm BB (1989) Ischemic damage in gerbil hippocampus is reduced following upregulation of adenosine (A1) receptors by caffeine treatment. Neurosci Lett 103:275–280PubMedCrossRefGoogle Scholar
  263. Rudolphi KA, Schubert P, Parkinson FE, Fredholm BB (1992) Adenosine and brain ischaemia. Cerebrovasc Brain Metab Rev 4:346–369PubMedGoogle Scholar
  264. Sajjadi FG, Takabayashi K, Foster AC, Domingo RC, Firestein GS (1996) Inhibition of TNF-α expression by adenosine: role of A3 adenosine receptors. J Immunol 156:3435–3442PubMedGoogle Scholar
  265. Saura J, Angulo E, Ejarque A, Casado V, Tusell JM, Moratalla R, Chen JF, Schwarzschild MA, Lluis C, Franco R, Serratosa J (2005) Adenosine A(2A) receptor stimulation potentiates nitric oxide release by activated microglia. J Neurochem 95:919–929PubMedCrossRefGoogle Scholar
  266. Scatena R, Martorana GE, Bottoni P, Botta G, Pastore P, Giardina B (2007) An update on pharmacological approaches to neurodegenerative diseases. Exp Opin Invest Drugs 16:59–72CrossRefGoogle Scholar
  267. Scattoni ML, Valanzano A, Pezzola A, De March Z, Fusco FR, Popoli P, Calamandrei G (2007) Adenosine A(2A) receptor blockade before striatal excitotoxic lesions prevents long term behavioural disturbances in the quinolinic rat model of Huntington’s disease. Behav Brain Res 176:216–221PubMedCrossRefGoogle Scholar
  268. Schiffmann SN, Jacobs O, Vanderhaegen JJ (1991) Striatal restricted adenosine A2 receptor (RDC8) is expressed by enkephalin but not by substance P neurons: an in situ hybridisation histochemistry study. J Neurochem 57:1062–1067PubMedCrossRefGoogle Scholar
  269. Schingnitz G, Kufnermuhl U, Ensinger H, Lehr E, Kuhn FJ (1991) Selective A1-antagonists for treatment of cognitive deficits. Nucleosides Nucleotides 10:1067–1076CrossRefGoogle Scholar
  270. Scholz KP, Miller RJ (1992) Inhibition of quantal transmitter release in the absence of calcium influx by a G protein-linked adenosine receptor at hippocampal synapses. Neuron 8:1139–1150PubMedCrossRefGoogle Scholar
  271. Schubert P, Ferroni S, Mager R (1991) Pharmacological blockade of chloride pumps on chloride channels reduces the adenosine-mediated depression of stimulus train-evoked calcium fluxes in rat hippocampal slices. Neurosci Lett 124:174–177PubMedCrossRefGoogle Scholar
  272. Schubert P, Ogata T, Ferroni S, McRae A, Nakamura Y, Rudolphi K (1996) Modulation of glial cell signaling by adenosine and pharmacological reinforcement: a neuroprotective strategy? Mol Chem Neuropathol 28:185–190PubMedCrossRefGoogle Scholar
  273. Schubert P, Ogata T, Rudolphi K, Marchini C, McRae A, Ferroni S (1997) Support of homeostatic glial cell signaling: a novel therapeutic approach by propentofylline. Ann NY Acad Sci 826:337–347PubMedCrossRefGoogle Scholar
  274. Schurr A, Reid KH, Tseng MT, West C, Rigor BM (1986) Adaptation of adult brain-tissue to anoxia and hypoxia invitro. Brain Res 374:244–248PubMedCrossRefGoogle Scholar
  275. Sebastiao AM, Ribeiro JA (1992) Evidence for the presence of excitatory A2 adenosine receptors in the rat hippocampus. Neurosci Lett 138:41–44PubMedCrossRefGoogle Scholar
  276. Sebastiao AM, Ribeiro JA (1996) Adenosine A(2) receptor-mediated excitatory actions on the nervous system. Progr Neurobiol 48:167–189CrossRefGoogle Scholar
  277. Sei Y, von Lubitz DKJE, Abbracchio MP, Ji X-D, Jacobson KA (1997) Adenosine A3 receptor agonist-induced neurotoxicity in rat cerebellar granule neurons. Drug Dev Res 40:267–273CrossRefGoogle Scholar
  278. Selley ML (2004) Increased homocysteine and decreased adenosine formation in Alzheimer’s disease. Neurol Res 26:554–557PubMedCrossRefGoogle Scholar
  279. Sheardown MJ, Knutsen LJS (1996) Unexpected neuroprotection observed with the adenosine A2A receptor agonist CGS21680. Drug Dev Res 39:108–114CrossRefGoogle Scholar
  280. Shen H, Zhang L, Yuen D, Logan R, Jung BP, Zhang G, Eubanks JH (2002) Expression and function of A1 adenosine receptors in the rat hippocampus following transient forebrain ischemia. Neuroscience 114:547–556PubMedCrossRefGoogle Scholar
  281. Simpson RE, O’Regan MH, Perkins LM, Phillis JW (1992) Excitatory transmitter amino acid release from the ischaemic rat cerebral cortex: effects of adenosine recptor agonists and antagonists. J Neurochem 58:1683–1690PubMedCrossRefGoogle Scholar
  282. Sperk G (1994) Kainic acid seizures in the rat. Prog Neurobiol 42:1–32PubMedCrossRefGoogle Scholar
  283. Spignoli G, Pedata F, Pepeu G (1984) A1 and A2 adenosine receptors modulate acetylcholine release from brain slices. Eur J Pharmacol 97:341–342PubMedCrossRefGoogle Scholar
  284. Stone TW (1993) The neuropharmacology of quinolinic acid and kynurenic acid. Pharmacol Rev 45:309–379PubMedGoogle Scholar
  285. Stone TW (2001) Kynurenines in the CNS: from endogenous obscurity to clinical relevance. Prog Neurobiol 64:185–218PubMedCrossRefGoogle Scholar
  286. Stone TW, Darlington LG (2002) Endogenous kynurenines as targets for drug discovery and development. Nat Rev Drug Discov 1:609–620PubMedCrossRefGoogle Scholar
  287. Stone TW, Perkins MN (1981) Quinolinic acid: a potent endogenous excitant at amino acid receptors in the CNS. Eur J Pharmacol 72:411–412PubMedCrossRefGoogle Scholar
  288. 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 42:171–182CrossRefGoogle Scholar
  289. Suzuki F, Shimada J, Shiozaki S, Ichikawa S, Ishii A, Nakamura J, Nonaka H, Kobayashi H, Fuse E (1993) Adenosine A1 antagonists. 3. Structure–activity relationships on amelioration against scopolamine- or N 6-((R)-phenylisopropyl)adenosine-induced cognitive disturbance. J Med Chem 36:2508–2518PubMedCrossRefGoogle Scholar
  290. Svenningsson P, Hall H, Sedvall G, Fredholm BB (1997) Distribution of adenosine receptors in the postmortem human brain: an extended autoradiographic study. Synapse 27:322–335PubMedCrossRefGoogle Scholar
  291. Szot P, Sanders RC, Murray TF (1987) Theophylline-induced up-regulation of adenosine-A1-receptors associated with reduced sensitivity to convulsants. Neuropharmacology 26: 1173–1180PubMedCrossRefGoogle Scholar
  292. Tarditi A, Camurri A, Varani K, Borea PA, Woodman B, Bates G, Cattaneo E, Abbracchio MP (2006) Early and transient alteration of adenosine A(2A) receptor signaling in a mouse model of Huntington disease. Neurobiol Dis 23:44–53PubMedCrossRefGoogle Scholar
  293. Tebano MT, Pintor A, Frank C, Domenici MR, Martire A, Pepponi R, Potenza RL, Grieco R, Popoli P (2004) Adenosine A(2A) receptor blockade differentially influences excitotoxic mechanisms at pre- and postsynaptic sites in the rat striatum. J Neurosci Res 77:100–107PubMedCrossRefGoogle Scholar
  294. Torres RJ, DeAntonio I, Prior C, Puig JG (2004) Effects of hypoxanthine on adenosine transport in human lymphocytes. Implications in the pathogenesis of Lesch–Nyhan syndrome. Nucleosides Nucleotides Nucl Acids 23:1177–1179CrossRefGoogle Scholar
  295. Traversa U, Rosati AM, Chiara F, Rodolfo V (1994) Effects of chronic administration of adenosine antagonists on adenosine A1 and A2A receptors in mouse brain. In vivo 8:1073–1078PubMedGoogle Scholar
  296. 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
  297. Trincavelli ML, Tonazzini I, Montali M, Abbracchio MP, Martini C (2008) Short-term TNF-α treatment induced A2B adenosine receptor desensitization in human astroglial cells. J Cell Biochem 104:150–161PubMedCrossRefGoogle Scholar
  298. Trussel LD, Jackson MB (1985) Adenosine activated potassium conductance in cultured striatal neurones. Proc Nat Acad Sci USA 82:4857–4861CrossRefGoogle Scholar
  299. Tsutsui S, Schnermann J, Noorbakhsh F, Henry S, Yong VW, Winston BW, Warren K, Power C (2004) A1 adenosine receptor upregulation and activation attenuates neuroinflammation and demyelination in a model of multiple sclerosis. J Neurosci 24:1521–1529PubMedCrossRefGoogle Scholar
  300. Ulas J, Brunner LC, Nguyen L, Cotman CW (1993) Reduced density of adenosine-A1-receptors and preserved coupling of adenosine-A1-receptors to G-proteins in Alzheimer hippocampus: a quantitative autoradiographic study. Neuroscience 52:843–854PubMedCrossRefGoogle Scholar
  301. Van der Schyf CJ, Gal S, Geldenhuys WJ, Youdim MBH (2006) Multifunctional neuroprotective drugs targeting monoamine oxidase inhibition, iron chelation, adenosine receptors, and cholinergic and glutamatergic action for neurodegenerative diseases. Expert Opin Invest Drugs 15:873- 886CrossRefGoogle Scholar
  302. van Gelder BM, Buijsse B, Tijhuis M, Kalmijn S, Giampaoli S, Nissinen A, Kromhout D (2007) Coffee consumption is inversely associated with cognitive decline in elderly European men: the FINE Study. Eur J Clin Nutr 61:226–232PubMedCrossRefGoogle Scholar
  303. Varani K, Gessi S, Dionisotti S, Ongini E, Borea PA (1998) [3H]-SCH58261 labelling of functional A2A receptors in human neutrophil membranes. Br J Pharmacol 123:1723–1731PubMedCrossRefGoogle Scholar
  304. Varani K, Rigamonti D, Sipione S, Camurri A, Borea PA, Cattabeni F, Abbracchio MP, Cattaneo E (2001) Aberrant amplification of A(2A) receptor signaling in striatal cells expressing mutant huntingtin. FASEB J 15:1245–1247PubMedGoogle Scholar
  305. Varani K, Abbracchio MP, Cannella M, Cislaghi G, Giallonardo P, Mariotti C, Cattabriga E, Cattabeni F, Borea PA, Squitieri F, Cattaneo E (2003) Aberrant A2A receptor function in peripheral blood cells in Huntington’s disease. FASEB J 17:2148–2150PubMedGoogle Scholar
  306. Varani K, Bachoud-Lévi AC, Mariotti C, Tarditi A, Abbracchio MP, Gasperi V, Borea PA, Dolbeau G, Gellera C, Solari A, Rosser A, Naji J, Handley O, Maccarrone M, Peschanski M, DiDonato S, Cattaneo E (2007) Biological abnormalities of peripheral A(2A) receptors in a large representation of polyglutamine disorders and Huntington’s disease stages. Neurobiol Dis 27:36–43PubMedCrossRefGoogle Scholar
  307. Virgili M, Poli A, Contestabile A, Migani P, Barnabei O (1986) Synaptosomal release of newly synthesised or recently accumulated amino acids; differential effects of kainic acid on naturally occurring excitatory amino acids and on [D-3H]-aspartate. Neurochem Int 9:29–33CrossRefPubMedGoogle Scholar
  308. Virus RM, Baglajewski T, Radulovacki M (1984) [3H]N 6-(L-Phenylisopropyl) adenosine binding in brains from young and old rats. Neurobiol Aging 5:61–62PubMedCrossRefGoogle Scholar
  309. von Lubitz DKEJ, Dambrosia JM, Redmond DJ (1989) Protective effect of cyclohexyladenosine in treatment of cerebral ischaemia in gerbils. Neuroscience 30:451–462CrossRefGoogle Scholar
  310. von Lubitz DK, Paul IA, Bartus RT, Jacobson KA (1993) Effects of chronic administration of adenosine A1 receptor agonist and antagonist on spatial learning and memory. Eur J Pharmacol 249:271–280CrossRefGoogle Scholar
  311. 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 ischaemia. Eur J Pharmacol 256:161–167CrossRefGoogle Scholar
  312. von Lubitz DK, Lin RC, Popik P, Carter MF, Jacobson KA (1994b) Adenosine A3 receptor stimulation and cerebral ischaemia. Eur J Pharmacol 263:59–67CrossRefGoogle Scholar
  313. von Lubitz DKJE, Kim J, Beenhakker M, Carter MF, Lin RCS, Meshulam Y, Daly JW, Shi D, Zhou LM, Jacobson KA (1995a) Chronic NMDA receptor stimulation: therapeutic implications of its effect on adenosine A(1) receptors. Eur J Pharmacol 283:185–192CrossRefGoogle Scholar
  314. von Lubitz DKJE, Lin RC-S, Jacobson KA (1995b) Cerebral ischaemia in gerbils: effects of acute and chronic treatment with adenosine A2A receptor agonist and antagonist. Eur J Pharmacol 287:295–302CrossRefGoogle Scholar
  315. 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 316:171–179CrossRefGoogle Scholar
  316. von Lubitz DJKE, Lin RCS, Bischofberger N, Beenhakker M, Boyd M, Lipartowska R, Jacobson KA (1999a) Protection against ischemic damage by adenosine amine congener, a potent and selective adenosine A1 receptor agonist. Eur J Pharmacol 369:313–317CrossRefGoogle Scholar
  317. von Lubitz DKJE, Lin RC-S, Boyd M, Bischofberger N, Jacobson KA (1999b) Chronic administration of adenosine A3 receptor agonist and cerebral ischaemia: neuronal and glial effects. Eur J Pharmacol 367:157–163CrossRefGoogle Scholar
  318. Von Lubitz DKJE, Simpson KL, Lin RCS (2001) Right thing at a wrong time? Adenosine A(3) receptors and cerebroprotection in stroke. Neuroprotective Agents 939:85–96Google Scholar
  319. Wagner DR, Combes A, McTiernan C, Sanders VJ, Lemster B, Feldman AM (1998a) Adenosine inhibits lipopolysaccharide-induced cardiac expression of TNFα. Circ Res 82:47–56PubMedGoogle Scholar
  320. Wagner DR, McTiernan C, Sanders VJ, Feldman AM (1998b) Adenosine inhibits lipopolysaccharide-induced secretion of TNF-α in the failing human heart. Circulation 97:521–524PubMedGoogle Scholar
  321. Warskulat U, Heller-Stilb B, Oermann E, Zilles K, Haas H, Lang F, Häussinger D (2007) Phenotype of the taurine transporter knockout mouse. Methods Enzymol 428:439–58PubMedCrossRefGoogle Scholar
  322. Wirkner K, Assmann H, Koles l, Gerevich Z, Franke H, Norenberg, Boehm R, Illes P (2000) Inhibition by adenosine A(2A) receptors of NMDA but not AMPA currents in rat neostriatal neurons. Br J Pharmacol 130:259–269PubMedCrossRefGoogle Scholar
  323. Wirkner K, Gerevich Z, Krause T, Gunther A, Koles L, Schneider D, Norenberg W, Illes P (2004) Adenosine A(2A) receptor-induced inhibition of NMDA and GABA(A) receptor-mediated synaptic currents in a subpopulation of rat striatal neurons. Neuropharmacology 46:994–1007PubMedCrossRefGoogle Scholar
  324. Wu LG, Saggau P (1997) Presynaptic inhibition of elicited neurotransmitter release. Trends Neurosci 20:204–212PubMedCrossRefGoogle Scholar
  325. Yamada K, Tanaka T, Senzaki K, Kameyama T, Nabeshima T (1998) Propentofylline improves learning and memory deficits in rats induced by β-amyloid protein-(1–40). Eur J Pharmacol 349:15–22PubMedCrossRefGoogle Scholar
  326. Yao ZH, Gross GJ (1994) The ATP-dependent potassium channel - an endogenous cardioprotective mechanism. J Cardiovasc Pharmacol 24: S28–S34PubMedCrossRefGoogle Scholar
  327. 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 232:317–22PubMedCrossRefGoogle Scholar
  328. Yoshida M, Nakakimura K, Cui YJ, Matsumoto M, Sakabe T (2004) Adenosine a, 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
  329. Yoshioka K, Saitoh O, and Nakata H (2001) Heteromeric association creates a P2Y-like adenosine receptor. Proc Natl Acad Sci USA 98:7617–7622PubMedCrossRefGoogle Scholar
  330. Yoshioka K, Hosada R, Kuroda Y, Nakata H (2002a) Hetero-oligomerization of adenosine A1 receptors with P2Y1 receptors in rat brains. FEBS Lett 531:299–303PubMedCrossRefGoogle Scholar
  331. Yoshioka K, Saitoh O, Nakata H (2002b) Agonist-promoted heteromeric oligomerization between adenosine A1 and P2Y1 receptors in living cells. FEBS Lett 523:147–151PubMedCrossRefGoogle Scholar
  332. Yu LQ, Huang Z, Mariani J, Wang Y, Moskowitz M, Chen JF (2004) 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
  333. Zarrindast MR, Shafaghi B (1994) Effects of adenosine receptor agonists and antagonists on acquisition of passive avoidance learning. Eur J Pharmacol 256:233–239PubMedCrossRefGoogle Scholar
  334. Zhao ZQ, McGee S, Nakanishi K, Toombs CF, Johnston WE, Ashar MS, Vinten-Johansen J (1993) Receptor-mediated cardioprotective effects of endogenous adenosine are exerted primarily during reperfusion after coronary occlusion in the rabbit. Circulation 88:709–719PubMedGoogle Scholar
  335. 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
  336. Zhou QY, Li C, Olah ME, Johnson RA, Stiles GL, Civelli O (1992) Molecular cloning and characterisation of an adenosine receptor: the A3 receptor. Proc Nat Acad Sci USA 89:7432–7436PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2009

Authors and Affiliations

  • Trevor W. Stone
    • 1
  • Stefania  Ceruti
    • 2
  • Mariapia P. Abbracchio
    • 2
  1. 1.Institute of Biomedical and Life SciencesUniversity of GlasgowGlasgowUK
  2. 2.Laboratory of Molecular and Cellular Pharmacology of Purinergic Transmission, Department of Pharmacological SciencesUniversity of MilanMilanItaly

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