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P2 receptors and neuronal injury

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Abstract

Extracellular adenosine 5′-triphosphate (ATP) was proposed to be an activity-dependent signaling molecule that regulates glia–glia and glia–neuron communications. ATP is a neurotransmitter of its own right and, in addition, a cotransmitter of other classical transmitters such as glutamate or GABA. The effects of ATP are mediated by two receptor families belonging either to the P2X (ligand-gated cationic channels) or P2Y (G protein-coupled receptors) types. P2X receptors are responsible for rapid synaptic responses, whereas P2Y receptors mediate slow synaptic responses and other types of purinergic signaling involved in neuronal damage/regeneration. ATP may act at pre- and postsynaptic sites and therefore, it may participate in the phenomena of long-term potentiation and long-term depression of excitatory synaptic transmission. The release of ATP into the extracellular space, e.g., by exocytosis, membrane transporters, and connexin hemichannels, is a widespread physiological process. However, ATP may also leave cells through their plasma membrane damaged by inflammation, ischemia, and mechanical injury. Functional responses to the activation of multiple P2 receptors were found in neurons and glial cells under normal and pathophysiological conditions. P2 receptor-activation could either be a cause or a consequence of neuronal cell death/glial activation and may be related to detrimental and/or beneficial effects. The present review aims at demonstrating that purinergic mechanisms correlate with the etiopathology of brain insults, especially because of the massive extracellular release of ATP, adenosine, and other neurotransmitters after brain injury. We will focus in this review on the most important P2 receptor-mediated neurodegenerative and neuroprotective processes and their beneficial modulation by possible therapeutic manipulations.

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Abbreviations

AA:

arachidonic acid

AD:

Alzheimer’s disease

AKT:

serine-threonine kinase AKT

AMPH:

d-amphetamine

ATP:

adenosine 5′ triphosphate

bFGF:

basic FGF

BrdU:

5-bromo-2′-deoxyuridine

BzATP:

benzoylbenzyl ATP

[Ca2+]i :

intracellular calcium

CNS:

central nervous system

COX:

cyclooxygenase

CysLT:

cysteinyl leukotrienes

DAG:

diacylglycerol

DRG:

dorsal root ganglion

EEG:

electroencephalogram

EGF:

epidermal growth factor

ERK1/2:

extracellular signal-regulated kinases 1 and 2

FGF:

fibroblast growth factor

GFAP:

glial fibrillary acidic protein

GFP:

green fluorescent protein

IL:

interleukin

IP3 :

inositol-(1,4,5)-triphosphate

IR:

immunoreactivity

JNKs:

c-Jun N-terminal kinases

LIF:

Leukemia inhibitory factor

LPS:

lipopolysaccharide

LTP:

long-term potentiation

LTD:

long-term depression

MAPK:

mitogen-activated protein kinase

MCAO:

middle cerebral artery occlusion

NAc:

nucleus accumbens

NFκB:

nuclear factor kappa B

NGF:

nerve growth factor

NO:

nitric oxide

NOS:

nitric oxide synthase

NPP:

nucleotide pyrophosphatase

oxATP:

adenosine 5′-triphosphate-2′,3′-dialdehyde

PC12:

clonal rat pheochromocytoma

PI3K:

phosphoinositide 3-kinase

PKB:

protein kinase B

PKC:

protein kinase C

PLA2 :

phospholipase A2

PLC:

phospholipase C

PLD:

phospholipase D

PPADS:

pyridoxalphosphate-6-azophenyl-2′,4′-disulfonic acid

SAPKs:

stress-activated protein kinases

SHR:

spontaneously hypertensive rat

SNARE:

soluble N-ethylmaleimide-sensitive factor attachment protein receptor

TGF-β:

transforming growth factor-beta

TNF:

tumor necrosis factor

TUNEL:

terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling

TrkA:

tyrosine receptor kinase A

VGLUT:

vesicular glutamate transporter

References

  1. Fields RD, Stevens-Graham B (2002) New insights into neuron–glia communication. Science 298:556–562

    PubMed  CAS  Google Scholar 

  2. Burnstock G (2004) Cotransmission. Curr Opin Pharmacol 4:47–52

    PubMed  CAS  Google Scholar 

  3. Ralevic V, Burnstock G (1998) Receptors for purines and pyrimidines. Pharmacol Rev 50:413–492

    PubMed  CAS  Google Scholar 

  4. Rathbone MP, Middlemiss PJ, Gysbers JW, Andrew C, Herman MA, Reed JK, Ciccarelli R, Di Iorio P, Caciagli F (1999) Trophic effects of purines in neurons and glial cells. Prog Neurobiol 59:663–690

    PubMed  CAS  Google Scholar 

  5. Volonte C, Amadio S, Cavaliere F, D’Ambrosi N, Vacca F, Bernardi G (2003) Extracellular ATP and neurodegeneration. Curr Drug Targets CNS Neurol Disord 2:403–412

    PubMed  CAS  Google Scholar 

  6. Franke H, Illes P (2006) Involvement of P2 receptors in the growth and survival of neurons in the CNS. Pharmacol Ther 109:297–324

    PubMed  CAS  Google Scholar 

  7. Dubyak GR, el-Moatassim C (1993) Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides. Am J Physiol 265:C577–C606

    PubMed  CAS  Google Scholar 

  8. Ferrari D, Chiozzi P, Falzoni S, Dal Susino M, Collo G, Buell G, Di Virgilio F (1997) ATP-mediated cytotoxicity in microglial cells. Neuropharmacology 36:1295–1301

    PubMed  CAS  Google Scholar 

  9. Bodin P, Burnstock G (1998) Increased release of ATP from endothelial cells during acute inflammation. Inflamm Res 47:351–354

    PubMed  CAS  Google Scholar 

  10. Neary JT, McCarthy M, Cornell-Bell A, Kang Y (1999) Trophic signaling pathways activated by purinergic receptors in rat and human astroglia. Prog Brain Res 120:323–332

    PubMed  CAS  Google Scholar 

  11. James G, Butt AM (2002) P2Y and P2X purinoceptor mediated Ca2+ signalling in glial cell pathology in the central nervous system. Eur J Pharmacol 447:247–260

    PubMed  CAS  Google Scholar 

  12. Amadio S, D’Ambrosi N, Cavaliere F, Murra B, Sancesario G, Bernardi G, Burnstock G, Volonte C (2002) P2 receptor modulation and cytotoxic function in cultured CNS neurons. Neuropharmacology 42:489–501

    PubMed  CAS  Google Scholar 

  13. D’Ambrosi N, Murra B, Cavaliere F, Amadio S, Bernardi G, Burnstock G, Volonte C (2001) Interaction between ATP and nerve growth factor signalling in the survival and neuritic outgrowth from PC12 cells. Neuroscience 108:527–534

    PubMed  CAS  Google Scholar 

  14. Neary JT, Zhu Q (1994) Signaling by ATP receptors in astrocytes. Neuroreport 5:1617–1620

    PubMed  CAS  Google Scholar 

  15. Abbracchio MP, Ceruti S, Barbieri D, Franceschi C, Malorni W, Biondo L, Burnstock G, Cattabeni F (1995) A novel action for adenosine: apoptosis of astroglial cells in rat brain primary cultures. Biochem Biophys Res Commun 213:908–915

    PubMed  CAS  Google Scholar 

  16. Kreutzberg GW (1996) Microglia: a sensor for pathological events in the CNS. Trends Neurosci 19:312–318

    PubMed  CAS  Google Scholar 

  17. Minghetti L, Polazzi E, Nicolini A, Greco A, Levi G (1999) Possible role of microglial prostanoids and free radicals in neuroprotection and neurodegeneration. Adv Exp Med Biol 468:109–119

    PubMed  CAS  Google Scholar 

  18. Gendron FP, Chalimoniuk M, Strosznajder J, Shen S, Gonzalez FA, Weisman GA, Sun GY (2003) P2X7 nucleotide receptor activation enhances IFN gamma-induced type II nitric oxide synthase activity in BV-2 microglial cells. J Neurochem 87:344–352

    PubMed  CAS  Google Scholar 

  19. Suzuki T, Hide I, Ido K, Kohsaka S, Inoue K, Nakata Y (2004) Production and release of neuroprotective tumor necrosis factor by P2X7 receptor-activated microglia. J Neurosci 24:1–7

    PubMed  CAS  Google Scholar 

  20. Marchetti B, Abbracchio MP (2005) To be or not to be (inflamed)—is that the question in anti-inflammatory drug therapy of neurodegenerative disorders? Trends Pharmacol Sci 26:517–525

    PubMed  CAS  Google Scholar 

  21. Silinsky EM (1975) On the association between transmitter secretion and the release of adenine nucleotides from mammalian motor nerve terminals. J Physiol 247:145–162

    PubMed  CAS  Google Scholar 

  22. Burnstock G (1986) Purines and cotransmitters in adrenergic and cholinergic neurones. Prog Brain Res 68:193–203

    PubMed  CAS  Google Scholar 

  23. Richardson PJ, Brown SJ (1987) ATP release from affinity-purified rat cholinergic nerve terminals. J Neurochem 48:622–630

    PubMed  CAS  Google Scholar 

  24. von Kügelgen I (1994) Purinoceptors modulating the release of noradrenaline. J Auton Pharmacol 14:11–12

    Google Scholar 

  25. Jo YH, Schlichter R (1999) Synaptic corelease of ATP and GABA in cultured spinal neurons. Nat Neurosci 2:241–245

    PubMed  CAS  Google Scholar 

  26. Jo YH, Role LW (2002) Coordinate release of ATP and GABA at in vitro synapses of lateral hypothalamic neurons. J Neurosci 22:4794–4804

    PubMed  CAS  Google Scholar 

  27. Rubio ME, Soto F (2001) Distinct localization of P2X receptors at excitatory postsynaptic specializations. J Neurosci 21:641–653

    PubMed  CAS  Google Scholar 

  28. Cunha RA, Vizi ES, Ribeiro JA, Sebastiao AM (1996) Preferential release of ATP and its extracellular catabolism as a source of adenosine upon high—but not low—frequency stimulation of rat hippocampal slices. J Neurochem 67:2180–2187

    Article  PubMed  CAS  Google Scholar 

  29. Vizi ES, Liang SD, Sperlagh B, Kittel A, Juranyi Z (1997) Studies on the release and extracellular metabolism of endogenous ATP in rat superior cervical ganglion: support for neurotransmitter role of ATP. Neuroscience 79:893–903

    PubMed  CAS  Google Scholar 

  30. Sperlagh B, Hasko G, Nemeth Z, Vizi ES (1998) ATP released by LPS increases nitric oxide production in raw 264.7 macrophage cell line via P2Z/P2X7 receptors. Neurochem Int 33:209–215

    PubMed  CAS  Google Scholar 

  31. Craig CG, White TD (1992) Low-level N-methyl-D-aspartate receptor activation provides a purinergic inhibitory threshold against further N-methyl-D-aspartate-mediated neurotransmission in the cortex. J Pharmacol Exp Ther 260:1278–1284

    PubMed  CAS  Google Scholar 

  32. Craig CG, White TD (1993) N-methyl-D-aspartate- and non-N-methyl-D-aspartate-evoked adenosine release from rat cortical slices: distinct purinergic sources and mechanisms of release. J Neurochem 60:1073–1080

    PubMed  CAS  Google Scholar 

  33. Gereau RW, Conn PJ (1994) Potentiation of cAMP responses by metabotropic glutamate receptors depresses excitatory synaptic transmission by a kinase-independent mechanism. Neuron 12:1121–1129

    PubMed  CAS  Google Scholar 

  34. Rosenberg PA, Li Y (1995) Adenylyl cyclase activation underlies intracellular cyclic AMP accumulation, cyclic AMP transport, and extracellular adenosine accumulation evoked by beta-adrenergic receptor stimulation in mixed cultures of neurons and astrocytes derived from rat cerebral cortex. Brain Res 692:227–232

    PubMed  CAS  Google Scholar 

  35. Pellegatti P, Falzoni S, Pinton P, Rizzuto R, Di Virgilio F (2005) A novel recombinant plasma membrane-targeted luciferase reveals a new pathway for ATP secretion. Mol Biol Cell 16:3659–3665

    PubMed  CAS  Google Scholar 

  36. Queiroz G, Meyer DK, Meyer A, Starke K, von Kügelgen I (1999) A study of the mechanism of the release of ATP from rat cortical astroglial cells evoked by activation of glutamate receptors. Neuroscience 91:1171–1181

    PubMed  CAS  Google Scholar 

  37. Cotrina ML, Lin JH, Lopez-Garcia JC, Naus CC, Nedergaard M (2000) ATP-mediated glia signaling. J Neurosci 20:2835–2844

    PubMed  CAS  Google Scholar 

  38. Arcuino G, Lin JH, Takano T, Liu C, Jiang L, Gao Q, Kang J, Nedergaard M (2002) Intercellular calcium signaling mediated by point-source burst release of ATP. Proc Natl Acad Sci USA 99:9840–9845

    PubMed  CAS  Google Scholar 

  39. Coco S, Calegari F, Pravettoni E, Pozzi D, Taverna E, Rosa P, Matteoli M, Verderio C (2003) Storage and release of ATP from astrocytes in culture. J Biol Chem 278:1354–1362

    PubMed  CAS  Google Scholar 

  40. Duan S, Anderson CM, Keung EC, Chen Y, Chen Y, Swanson RA (2003) P2X7 receptor-mediated release of excitatory amino acids from astrocytes. J Neurosci 23:1320–1328

    PubMed  CAS  Google Scholar 

  41. Newman EA (2003) New roles for astrocytes: regulation of synaptic transmission. Trends Neurosci 26:536–542

    PubMed  CAS  Google Scholar 

  42. Scemes E, Duval N, Meda P (2003) Reduced expression of P2Y1 receptors in connexin43-null mice alters calcium signaling and migration of neural progenitor cells. J Neurosci 23:11444–11452

    PubMed  CAS  Google Scholar 

  43. Burnstock G (1997) The past, present and future of purine nucleotides as signalling molecules. Neuropharmacology 36:1127–1139

    PubMed  CAS  Google Scholar 

  44. Rothman JE (1994) Mechanisms of intracellular protein transport. Nature 372:55–63

    PubMed  CAS  Google Scholar 

  45. Rettig J, Neher E (2002) Emerging roles of presynaptic proteins in Ca2+-triggered exocytosis. Science 298:781–785

    PubMed  CAS  Google Scholar 

  46. Lazarowski ER, Boucher RC, Harden TK (2003) Mechanisms of release of nucleotides and integration of their action as P2X- and P2Y-receptor activating molecules. Mol Pharmacol 64:785–795

    PubMed  CAS  Google Scholar 

  47. Prat AG, Reisin IL, Ausiello DA, Cantiello HF (1996) Cellular ATP release by the cystic fibrosis transmembrane conductance regulator. Am J Physiol 270:C538–C545

    PubMed  CAS  Google Scholar 

  48. Naumann N, Siratska O, Gahr M, Rosen-Wolff A (2005) P-glycoprotein expression increases ATP release in respiratory cystic fibrosis cells. J Cyst Fibros 4:157–168

    PubMed  CAS  Google Scholar 

  49. Cotrina ML, Lin JH, Alves-Rodrigues A, Liu S, Li J, Azmi-Ghadimi H, Kang J, Naus CC, Nedergaard M (1998) Connexins regulate calcium signaling by controlling ATP release. Proc Natl Acad Sci USA 95:15735–15740

    PubMed  CAS  Google Scholar 

  50. De Vuyst E, Decrock E, Cabooter L, Dubyak GR, Naus CC, Evans WH, Leybaert L (2006) Intracellular calcium changes trigger connexin 32 hemichannel opening. EMBO J 25:34–44

    PubMed  Google Scholar 

  51. Crompton M (1999) The mitochondrial permeability transition pore and its role in cell death. Biochem J 341(Pt 2):233–249

    PubMed  CAS  Google Scholar 

  52. Okada SF, O’Neal WK, Huang P, Nicholas RA, Ostrowski LE, Craigen WJ, Lazarowski ER, Boucher RC (2004) Voltage-dependent anion channel-1 (VDAC-1) contributes to ATP release and cell volume regulation in murine cells. J Gen Physiol 124:513–526

    PubMed  CAS  Google Scholar 

  53. Boudreault F, Grygorczyk R (2002) Cell swelling-induced ATP release and gadolinium-sensitive channels. Am J Physiol Cell Physiol 282:C219–C226

    PubMed  CAS  Google Scholar 

  54. Lazarowski ER, Boucher RC, Harden TK (2000) Constitutive release of ATP and evidence for major contribution of ecto-nucleotide pyrophosphatase and nucleoside diphosphokinase to extracellular nucleotide concentrations. J Biol Chem 275:31061–31068

    PubMed  CAS  Google Scholar 

  55. Casel D, Brockhaus J, Deitmer JW (2005) Enhancement of spontaneous synaptic activity in rat Purkinje neurones by ATP during development. J Physiol 568:111–122

    PubMed  CAS  Google Scholar 

  56. Bodin P, Burnstock G (2001) Purinergic signalling: ATP release. Neurochem Res 26:959–969

    PubMed  CAS  Google Scholar 

  57. Kaczmarek E, Koziak K, Sevigny J, Siegel JB, Anrather J, Beaudoin AR, Bach FH, Robson SC (1996) Identification and characterization of CD39/vascular ATP diphosphohydrolase. J Biol Chem 271:33116–33122

    PubMed  CAS  Google Scholar 

  58. Wang TF, Guidotti G (1996) CD39 is an ecto-(Ca2+, Mg2+)-apyrase. J Biol Chem 271:9898–9901

    PubMed  CAS  Google Scholar 

  59. Zimmermann H, Braun N (1999) Ecto-nucleotidases—molecular structures, catalytic properties, and functional roles in the nervous system. Prog Brain Res 120:371–385

    PubMed  CAS  Google Scholar 

  60. Beaudoin AR, Grondin G, Gendron FP (1999) Immunolocalization of ATP diphosphohydrolase in pig and mouse brains, and sensory organs of the mouse. Prog Brain Res 120:387–395

    PubMed  CAS  Google Scholar 

  61. Dunwiddie TV, Diao L, Proctor WR (1997) Adenine nucleotides undergo rapid, quantitative conversion to adenosine in the extracellular space in rat hippocampus. J Neurosci 17:7673–7682

    PubMed  CAS  Google Scholar 

  62. Zimmermann H (2000) Extracellular metabolism of ATP and other nucleotides. Naunyn Schmiedebergs Arch Pharmacol 362:299–309

    PubMed  CAS  Google Scholar 

  63. Shukla V, Zimmermann H, Wang L, Kettenmann H, Raab S, Hammer K, Sevigny J, Robson SC, Braun N (2005) Functional expression of the ecto-ATPase NTPDase2 and of nucleotide receptors by neuronal progenitor cells in the adult murine hippocampus. J Neurosci Res 80:600–610

    PubMed  CAS  Google Scholar 

  64. Agteresch HJ, Dagnelie PC, van den Berg JW, Wilson JH (1999) Adenosine triphosphate: established and potential clinical applications. Drugs 58:211–232

    PubMed  CAS  Google Scholar 

  65. Schwiebert EM (2000) Extracellular ATP-mediated propagation of Ca2+ waves. Focus on “mechanical strain-induced Ca2+ waves are propagated via ATP release and purinergic receptor activation”. Am J Physiol Cell Physiol 279:C281–C283

    PubMed  CAS  Google Scholar 

  66. Franke H, Grummich B, Härtig W, Grosche J, Regenthal R, Edwards RH, Illes P, Krügel U (2006) Changes in purinergic signaling after cerebral injury—involvement of glutamatergic mechanisms? Int J Dev Neurosci 24:123–132

    PubMed  CAS  Google Scholar 

  67. 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 49:227–231

    PubMed  CAS  Google Scholar 

  68. Gordon JL (1986) Extracellular ATP: effects, sources and fate. Biochem J 233:309–319

    PubMed  CAS  Google Scholar 

  69. Deuticke B, Gerlach E, Dierkesmann R (1966) Decomposition of free nucleotides in the rat heart, skeletal muscle, brain and liver in oxygen deficiency. Pflügers Arch Gesamte Physiol Menschen Tiere 292:239–254

    PubMed  CAS  Google Scholar 

  70. Ferguson DR, Kennedy I, Burton TJ (1997) ATP is released from rabbit urinary bladder epithelial cells by hydrostatic pressure changes—a possible sensory mechanism? J Physiol 505(Pt 2):503–511

    PubMed  CAS  Google Scholar 

  71. Okada Y, Maeno E, Shimizu T, Dezaki K, Wang J, Morishima S (2001) Receptor-mediated control of regulatory volume decrease (RVD) and apoptotic volume decrease (AVD). J Physiol 532:3–16

    PubMed  CAS  Google Scholar 

  72. Wang EC, Lee JM, Ruiz WG, Balestreire EM, von Bodungen M, Barrick S, Cockayne DA, Birder LA, Apodaca G (2005) ATP and purinergic receptor-dependent membrane traffic in bladder umbrella cells. J Clin Invest 115:2412–2422

    PubMed  CAS  Google Scholar 

  73. Hamada K, Takuwa N, Yokoyama K, Takuwa Y (1998) Stretch activates Jun N-terminal kinase/stress-activated protein kinase in vascular smooth muscle cells through mechanisms involving autocrine ATP stimulation of purinoceptors. J Biol Chem 273:6334–6340

    PubMed  CAS  Google Scholar 

  74. Yang S, Cheek DJ, Westfall DP, Buxton IL (1994) Purinergic axis in cardiac blood vessels. Agonist-mediated release of ATP from cardiac endothelial cells. Circ Res 74:401–407

    PubMed  CAS  Google Scholar 

  75. Ostrom RS, Gregorian C, Insel PA (2000) Cellular release of and response to ATP as key determinants of the set-point of signal transduction pathways. J Biol Chem 275:11735–11739

    PubMed  CAS  Google Scholar 

  76. Gourine AV, Llaudet E, Dale N, Spyer KM (2005) ATP is a mediator of chemosensory transduction in the central nervous system. Nature 436:108–111

    PubMed  CAS  Google Scholar 

  77. Braun N, Zhu Y, Krieglstein J, Culmsee C, Zimmermann H (1998) Upregulation of the enzyme chain hydrolyzing extracellular ATP after transient forebrain ischemia in the rat. J Neurosci 18:4891–4900

    PubMed  CAS  Google Scholar 

  78. Melani A, Turchi D, Vannucchi MG, Cipriani S, Gianfriddo M, Pedata F (2005) ATP extracellular concentrations are increased in the rat striatum during in vivo ischemia. Neurochem Int 47:442–448

    PubMed  CAS  Google Scholar 

  79. Wang X, Arcuino G, Takano T, Lin J, Peng WG, Wan P, Li P, Xu Q, Liu QS, Goldman SA, Nedergaard M (2004) P2X7 receptor inhibition improves recovery after spinal cord injury. Nat Med 10:821–827

    PubMed  CAS  Google Scholar 

  80. Wieraszko A, Seyfried TN (1989) Increased amount of extracellular ATP in stimulated hippocampal slices of seizure prone mice. Neurosci Lett 106:287–293

    PubMed  CAS  Google Scholar 

  81. Edwards FA (1996) Features of P2X receptor-mediated synapses in the rat brain: why doesn’t ATP kill the postsynaptic cell? Ciba Found Symp 198:278–286

    PubMed  CAS  Google Scholar 

  82. Robson SC, Kaczmarek E, Siegel JB, Candinas D, Koziak K, Millan M, Hancock WW, Bach FH (1997) Loss of ATP diphosphohydrolase activity with endothelial cell activation. J Exp Med 185:153–163

    PubMed  CAS  Google Scholar 

  83. Zimmermann H (1996) Biochemistry, localization and functional roles of ecto-nucleotidases in the nervous system. Prog Neurobiol 49:589–618

    PubMed  CAS  Google Scholar 

  84. Abbracchio MP, Boeynaems JM, Barnard EA, Boyer JL, Kennedy C, Miras-Portugal MT, King BF, Gachet C, Jacobson KA, Weisman GA, Burnstock G (2003) Characterization of the UDP-glucose receptor (re-named here the P2Y14 receptor) adds diversity to the P2Y receptor family. Trends Pharmacol Sci 24:52–55

    PubMed  CAS  Google Scholar 

  85. von Kügelgen I (2006) Pharmacological profiles of cloned mammalian P2Y-receptor subtypes. Pharmacol Ther (in press)

  86. Rodrigues RJ, Almeida T, Richardson PJ, Oliveira CR, Cunha RA (2005) Dual presynaptic control by ATP of glutamate release via facilitatory P2X1, P2X2/3, and P2X3 and inhibitory P2Y1, P2Y2, and/or P2Y4 receptors in the rat hippocampus. J Neurosci 25:6286–6295

    PubMed  CAS  Google Scholar 

  87. Rundén-Pran E, Tanso R, Haug FM, Ottersen OP, Ring A (2005) Neuroprotective effects of inhibiting N-methyl-d-aspartate receptors, P2X receptors and the mitogen-activated protein kinase cascade: a quantitative analysis in organotypical hippocampal slice cultures subjected to oxygen and glucose deprivation. Neuroscience 136:795–810

    PubMed  Google Scholar 

  88. Illes P, Ribeiro JA (2004) Neuronal P2 receptors of the central nervous system. Curr Top Med Chem 4:831–838

    PubMed  CAS  Google Scholar 

  89. Nörenberg W, Illes P (2000) Neuronal P2X receptors: localisation and functional properties. Naunyn Schmiedebergs Arch Pharmacol 362:324–339

    PubMed  Google Scholar 

  90. Khakh BS, Burnstock G, Kennedy C, King BF, North RA, Seguela P, Voigt M, Humphrey PP (2001) International union of pharmacology. XXIV. Current status of the nomenclature and properties of P2X receptors and their subunits. Pharmacol Rev 53:107–118

    PubMed  CAS  Google Scholar 

  91. North RA (2002) Molecular physiology of P2X receptors. Physiol Rev 82:1013–1067

    PubMed  CAS  Google Scholar 

  92. Burnstock G (2006) Purinergic signalling. Br J Pharmacol 147:S172–S181

    PubMed  CAS  Google Scholar 

  93. Communi D, Robaye B, Boeynaems JM (1999) Pharmacological characterization of the human P2Y11 receptor. Br J Pharmacol 128:1199–1206

    PubMed  CAS  Google Scholar 

  94. Communi D, Gonzalez NS, Detheux M, Brezillon S, Lannoy V, Parmentier M, Boeynaems JM (2001) Identification of a novel human ADP receptor coupled to Gi. J Biol Chem 276:41479–41485

    PubMed  CAS  Google Scholar 

  95. Hollopeter G, Jantzen HM, Vincent D, Li G, England L, Ramakrishnan V, Yang RB, Nurden P, Nurden A, Julius D, Conley PB (2001) Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 409:202–207

    PubMed  CAS  Google Scholar 

  96. Nakata H, Yoshioka K, Kamiya T, Tsuga H, Oyanagi K (2005) Functions of heteromeric association between adenosine and P2Y receptors. J Mol Neurosci 26:233–238

    PubMed  CAS  Google Scholar 

  97. von Kügelgen I, Wetter A (2000) Molecular pharmacology of P2Y-receptors. Naunyn Schmiedebergs Arch Pharmacol 362:310–323

    Google Scholar 

  98. Abbracchio MP, Brambilla R, Ceruti S, Cattabeni F (1999) Signalling mechanisms involved in P2Y receptor-mediated reactive astrogliosis. Prog Brain Res 120:333–342

    PubMed  CAS  Google Scholar 

  99. Neary JT, Kang Y, Bu Y, Yu E, Akong K, Peters CM (1999) Mitogenic signaling by ATP/P2Y purinergic receptors in astrocytes: involvement of a calcium-independent protein kinase C, extracellular signal-regulated protein kinase pathway distinct from the phosphatidylinositol-specific phospholipase C/calcium pathway. J Neurosci 19:4211–4220

    PubMed  CAS  Google Scholar 

  100. Brambilla R, Abbracchio MP (2001) Modulation of cyclooxygenase-2 and brain reactive astrogliosis by purinergic P2 receptors. Ann N Y Acad Sci 939:54–62

    Article  PubMed  CAS  Google Scholar 

  101. Reiser G (1995) Ca2+- and nitric oxide-dependent stimulation of cyclic GMP synthesis in neuronal cell line induced by P2-purinergic/pyrimidinergic receptor. J Neurochem 64:61–68

    Article  PubMed  CAS  Google Scholar 

  102. Kittner H, Franke H, Fischer W, Schultheis N, Krügel U, Illes P (2003) Stimulation of P2Y1 receptors causes anxiolytic-like effects in the rat elevated plus-maze: implications for the involvement of P2Y1 receptor-mediated nitric oxide production. Neuropsychopharmacology 28:435–444

    PubMed  CAS  Google Scholar 

  103. Viscomi MT, Florenzano F, Conversi D, Bernardi G, Molinari M (2004) Axotomy dependent purinergic and nitrergic co-expression. Neuroscience 123:393–404

    PubMed  CAS  Google Scholar 

  104. Neary JT, Whittemore SR, Zhu Q, Norenberg MD (1994) Synergistic activation of DNA synthesis in astrocytes by fibroblast growth factors and extracellular ATP. J Neurochem 63:490–494

    Article  PubMed  CAS  Google Scholar 

  105. Neary JT, Zhu Q, Kang Y, Dash PK (1996) Extracellular ATP induces formation of AP-1 complexes in astrocytes via P2 purinoceptors. Neuroreport 7:2893–2896

    PubMed  CAS  Google Scholar 

  106. Swanson KD, Reigh C, Landreth GE (1998) ATP-stimulated activation of the mitogen-activated protein kinases through ionotropic P2X2 purinoreceptors in PC12 cells. Difference in purinoreceptor sensitivity in two PC12 cell lines. J Biol Chem 273:19965–19971

    PubMed  CAS  Google Scholar 

  107. D’Ambrosi N, Cavaliere F, Merlo D, Milazzo L, Mercanti D, Volonte C (2000) Antagonists of P2 receptor prevent NGF-dependent neuritogenesis in PC12 cells. Neuropharmacology 39:1083–1094

    PubMed  CAS  Google Scholar 

  108. D’Ambrosi N, Murra B, Vacca F, Volonte C (2004) Pathways of survival induced by NGF and extracellular ATP after growth factor deprivation. Prog Brain Res 146:93–100

    PubMed  CAS  Google Scholar 

  109. Soltoff SP, Avraham H, Avraham S, Cantley LC (1998) Activation of P2Y2 receptors by UTP and ATP stimulates mitogen-activated kinase activity through a pathway that involves related adhesion focal tyrosine kinase and protein kinase C. J Biol Chem 273:2653–2660

    PubMed  CAS  Google Scholar 

  110. Neary JT, Kang Y, Shi YF (2004) Signaling from nucleotide receptors to protein kinase cascades in astrocytes. Neurochem Res 29:2037–2042

    PubMed  CAS  Google Scholar 

  111. Neary JT, Kang Y (2005) Signaling from P2 nucleotide receptors to protein kinase cascades induced by CNS injury: implications for reactive gliosis and neurodegeneration. Mol Neurobiol 31:95–103

    PubMed  CAS  Google Scholar 

  112. Wang M, Kong Q, Gonzalez FA, Sun G, Erb L, Seye C, Weisman GA (2005) P2Y nucleotide receptor interaction with alpha integrin mediates astrocyte migration. J Neurochem 95:630–640

    PubMed  CAS  Google Scholar 

  113. Gonzalez FA, Weisman GA, Erb L, Seye CI, Sun GY, Velazquez B, Hernandez-Perez M, Chorna NE (2005) Mechanisms for inhibition of P2 receptors signaling in neural cells. Mol Neurobiol 31:65–79

    PubMed  CAS  Google Scholar 

  114. Weisman GA, Wang M, Kong Q, Chorna NE, Neary JT, Sun GY, Gonzalez FA, Seye CI, Erb L (2005) Molecular determinants of P2Y2 nucleotide receptor function: implications for proliferative and inflammatory pathways in astrocytes. Mol Neurobiol 31:169–183

    PubMed  CAS  Google Scholar 

  115. Ryu JK, Choi HB, Hatori K, Heisel RL, Pelech SL, McLarnon JG, Kim SU (2003) Adenosine triphosphate induces proliferation of human neural stem cells: role of calcium and p70 ribosomal protein S6 kinase. J Neurosci Res 72:352–362

    PubMed  CAS  Google Scholar 

  116. Cunha RA, Ribeiro JA (2000) ATP as a presynaptic modulator. Life Sci 68:119–137

    PubMed  CAS  Google Scholar 

  117. Pankratov YV, Lalo UV, Krishtal OA (2002) Role for P2X receptors in long-term potentiation. J Neurosci 22:8363–8369

    PubMed  CAS  Google Scholar 

  118. Deuchars SA, Atkinson L, Brooke RE, Musa H, Milligan CJ, Batten TF, Buckley NJ, Parson SH, Deuchars J (2001) Neuronal P2X7 receptors are targeted to presynaptic terminals in the central and peripheral nervous systems. J Neurosci 21:7143–7152

    PubMed  CAS  Google Scholar 

  119. Diaz-Hernandez M, Gomez-Villafuertes R, Hernando F, Pintor J, Miras-Portugal MT (2001) Presence of different ATP receptors on rat midbrain single synaptic terminals. Involvement of the P2X3 subunits. Neurosci Lett 301:159–162

    PubMed  CAS  Google Scholar 

  120. Schäfer R, Reiser G (1997) Characterization of [35S]-ATP alpha S and [3H]-alpha, beta-MeATP binding sites in rat brain cortical synaptosomes: regulation of ligand binding by divalent cations. Br J Pharmacol 121:913–922

    PubMed  Google Scholar 

  121. Simon J, Webb TE, Barnard EA (1997) Distribution of [35S]dATP alpha S binding sites in the adult rat neuraxis. Neuropharmacology 36:1243–1251

    PubMed  CAS  Google Scholar 

  122. Gu JG, MacDermott AB (1997) Activation of ATP P2X receptors elicits glutamate release from sensory neuron synapses. Nature 389:749–753

    PubMed  CAS  Google Scholar 

  123. Zimmermann H (1994) Signalling via ATP in the nervous system. Trends Neurosci 17:420–426

    PubMed  CAS  Google Scholar 

  124. Wieraszko A, Goldsmith G, Seyfried TN (1989) Stimulation-dependent release of adenosine triphosphate from hippocampal slices. Brain Res 485:244–250

    PubMed  CAS  Google Scholar 

  125. Choi DW (1988) Glutamate neurotoxicity and diseases of the nervous system. Neuron 1:623–634

    PubMed  CAS  Google Scholar 

  126. Parpura V, Basarsky TA, Liu F, Jeftinija K, Jeftinija S, Haydon PG (1994) Glutamate-mediated astrocyte-neuron signalling. Nature 369:744–747

    PubMed  CAS  Google Scholar 

  127. Jeremic A, Jeftinija K, Stevanovic J, Glavaski A, Jeftinija S (2001) ATP stimulates calcium-dependent glutamate release from cultured astrocytes. J Neurochem 77:664–675

    PubMed  CAS  Google Scholar 

  128. Araque A, Carmignoto G, Haydon PG (2001) Dynamic signaling between astrocytes and neurons. Annu Rev Physiol 63:795–813

    PubMed  CAS  Google Scholar 

  129. Bezzi P, Gundersen V, Galbete JL, Seifert G, Steinhauser C, Pilati E, Volterra A (2004) Astrocytes contain a vesicular compartment that is competent for regulated exocytosis of glutamate. Nat Neurosci 7:613–620

    PubMed  CAS  Google Scholar 

  130. Fellin T, Pozzan T, Carmignoto G (2006) Purinergic receptors mediate two distinct glutamate release pathways in hippocampal astrocytes. J Biol Chem 281:4274–4284

    PubMed  CAS  Google Scholar 

  131. Khakh BS, Gittermann D, Cockayne DA, Jones A (2003) ATP modulation of excitatory synapses onto interneurons. J Neurosci 23:7426–7437

    PubMed  CAS  Google Scholar 

  132. Kawamura M, Gachet C, Inoue K, Kato F (2004) Direct excitation of inhibitory interneurons by extracellular ATP mediated by P2Y1 receptors in the hippocampal slice. J Neurosci 24:10835–10845

    PubMed  CAS  Google Scholar 

  133. Kukley M, Stausberg P, Adelmann G, Chessell IP, Dietrich D (2004) Ecto-nucleotidases and nucleoside transporters mediate activation of adenosine receptors on hippocampal mossy fibers by P2X7 receptor agonist 2′-3′-O-(4-benzoylbenzyl)-ATP. J Neurosci 24:7128–7139

    PubMed  CAS  Google Scholar 

  134. Fredholm BB, Chen JF, Cunha RA, Svenningsson P, Vaugeois JM (2005) Adenosine and brain function. Int Rev Neurobiol 63:191–270

    PubMed  CAS  Google Scholar 

  135. Mendoza-Fernandez V, Andrew RD, Barajas-Lopez C (2000) ATP inhibits glutamate synaptic release by acting at P2Y receptors in pyramidal neurons of hippocampal slices. J Pharmacol Exp Ther 293:172–179

    PubMed  CAS  Google Scholar 

  136. Masino SA, Diao L, Illes P, Zahniser NR, Larson GA, Johansson B, Fredholm BB, Dunwiddie TV (2002) Modulation of hippocampal glutamatergic transmission by ATP is dependent on adenosine A1 receptors. J Pharmacol Exp Ther 303:356–363

    PubMed  CAS  Google Scholar 

  137. Cunha RA, Sebastiao AM, Ribeiro JA (1998) Inhibition by ATP of hippocampal synaptic transmission requires localized extracellular catabolism by ecto-nucleotidases into adenosine and channeling to adenosine A1 receptors. J Neurosci 18:1987–1995

    PubMed  CAS  Google Scholar 

  138. Zhang JM, Wang HK, Ye CQ, Ge W, Chen Y, Jiang ZL, Wu CP, Poo MM, Duan S (2003) ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression. Neuron 40:971–982

    PubMed  CAS  Google Scholar 

  139. Krügel U, Schraft T, Regenthal R, Illes P, Kittner H (2004) Purinergic modulation of extracellular glutamate levels in the nucleus accumbens in vivo. Int J Dev Neurosci 22:565–570

    PubMed  Google Scholar 

  140. Krügel U, Spiess O, Regenthal R, Illes P, Kittner H (2004) P2 receptors are involved in the mediation of motivation-related behaviour. Purinergic Signalling 1:21–29

    PubMed  Google Scholar 

  141. Danbolt NC (2001) Glutamate uptake. Prog Neurobiol 65:1–105

    PubMed  CAS  Google Scholar 

  142. Burnstock G (1996) Purinoceptors: ontogeny and phylogeny. Drug Dev Res 39:204–242

    CAS  Google Scholar 

  143. Abbracchio MP, Ceruti S, Langfelder R, Cattabeni F, Saffrey MJ, Burnstock G (1995) Effects of ATP analogues and basic fibroblast growth factor on astroglial cell differentiation in primary cultures of rat striatum. Int J Dev Neurosci 13:685–693

    PubMed  CAS  Google Scholar 

  144. Lemoli RM, Ferrari D, Fogli M, Rossi L, Pizzirani C, Forchap S, Chiozzi P, Vaselli D, Bertolini F, Foutz T, Aluigi M, Baccarani M, Di Virgilio F (2004) Extracellular nucleotides are potent stimulators of human hematopoietic stem cells in vitro and in vivo. Blood 104:1662–1670

    PubMed  CAS  Google Scholar 

  145. Lenz G, Gottfried C, Luo Z, Avruch J, Rodnight R, Nie WJ, Kang Y, Neary JT (2000) P2Y purinoceptor subtypes recruit different mek activators in astrocytes. Br J Pharmacol 129:927–936

    PubMed  CAS  Google Scholar 

  146. Arthur DB, Akassoglou K, Insel PA (2005) P2Y2 receptor activates nerve growth factor/TrkA signaling to enhance neuronal differentiation. Proc Natl Acad Sci USA 102:19138–19143

    PubMed  CAS  Google Scholar 

  147. Hogg RC, Chipperfield H, Whyte KA, Stafford MR, Hansen MA, Cool SM, Nurcombe V, Adams DJ (2004) Functional maturation of isolated neural progenitor cells from the adult rat hippocampus. Eur J Neurosci 19:2410–2420

    PubMed  Google Scholar 

  148. Agresti C, Meomartini ME, Amadio S, Ambrosini E, Serafini B, Franchini L, Volonte C, Aloisi F, Visentin S (2005) Metabotropic P2 receptor activation regulates oligodendrocyte progenitor migration and development. Glia 50:132–144

    PubMed  CAS  Google Scholar 

  149. Agresti C, Meomartini ME, Amadio S, Ambrosini E, Volonte C, Aloisi F, Visentin S (2005) ATP regulates oligodendrocyte progenitor migration, proliferation, and differentiation: involvement of metabotropic P2 receptors. Brain Res Brain Res Rev 48:157–165

    PubMed  CAS  Google Scholar 

  150. Lutz PL, Kabler S (1997) Release of adenosine and ATP in the brain of the freshwater turtle (Trachemys scripta) during long-term anoxia. Brain Res 769:281–286

    PubMed  CAS  Google Scholar 

  151. Petruzzi E, Orlando C, Pinzani P, Sestini R, Del Rosso A, Dini G, Tanganelli E, Buggiani A, Pazzagli M (1994) Adenosine triphosphate release by osmotic shock and hemoglobin A1C in diabetic subjects’ erythrocytes. Metabolism 43:435–440

    PubMed  CAS  Google Scholar 

  152. Cavaliere F, D’Ambrosi N, Ciotti MT, Mancino G, Sancesario G, Bernardi G, Volonte C (2001) Glucose deprivation and chemical hypoxia: neuroprotection by P2 receptor antagonists. Neurochem Int 38:189–197

    PubMed  CAS  Google Scholar 

  153. Cavaliere F, D’Ambrosi N, Sancesario G, Bernardi G, Volonte C (2001) Hypoglycaemia-induced cell death: features of neuroprotection by the P2 receptor antagonist basilen blue. Neurochem Int 38:199–207

    PubMed  CAS  Google Scholar 

  154. Chow SC, Kass GEN, Orrenius S (1997) Purines and their roles in apoptosis. Neuropharmacology 36:1149–1156

    PubMed  CAS  Google Scholar 

  155. Abbracchio MP, Burnstock G (1998) Purinergic signalling: pathophysiological roles. Jpn J Pharmacol 78:113–145

    PubMed  CAS  Google Scholar 

  156. Burnstock G (1999) Current status of purinergic signalling in the nervous system. Prog Brain Res 120:3–10

    PubMed  CAS  Google Scholar 

  157. Ryu JK, Kim J, Choi SH, Oh YJ, Lee YB, Kim SU, Jin BK (2002) ATP-induced in vivo neurotoxicity in the rat striatum via P2 receptors. Neuroreport 13:1611–1615

    PubMed  CAS  Google Scholar 

  158. Choi D (1998) Antagonizing excitotoxicity: a therapeutic strategy for stroke? Mt Sinai J Med 65:133–138

    PubMed  CAS  Google Scholar 

  159. Watkins JC, Collingridge GL (1989) The NMDA receptor. Oxford University Press, London, UK

    Google Scholar 

  160. Norenberg MD (1994) Astrocyte responses to CNS injury. J Neuropathol Exp Neurol 53:213–220

    PubMed  CAS  Google Scholar 

  161. Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: GFAP—thirty-one years (1969–2000). Neurochem Res 25:1439–1451

    PubMed  CAS  Google Scholar 

  162. McGraw J, Hiebert GW, Steeves JD (2001) Modulating astrogliosis after neurotrauma. J Neurosci Res 63:109–115

    PubMed  CAS  Google Scholar 

  163. Pekovi S, Filipovic R, Subasic S, Lavrnja I, Stojkov D, Nedeljkovic N, Rakic L, Stojiljkovic M (2005) Downregulation of glial scarring after brain injury: the effect of purine nucleoside analogue ribavirin. Ann N Y Acad Sci 1048:296–310

    PubMed  Google Scholar 

  164. Frederickson RC (1992) Astroglia in Alzheimer’s disease. Neurobiol Aging 13:239–253

    PubMed  CAS  Google Scholar 

  165. Franke H (1995) Influence of chronic alcohol treatment on the GFAP-immunoreactivity in astrocytes of the hippocampus in rats. Acta Histochem 97:263–271

    PubMed  CAS  Google Scholar 

  166. D’Amelio FE, Smith ME, Eng LF (1990) Sequence of tissue responses in the early stages of experimental allergic encephalomyelitis (EAE): immunohistochemical, light microscopic, and ultrastructural observations in the spinal cord. Glia 3:229–240

    PubMed  CAS  Google Scholar 

  167. Koizumi S, Fujishita K, Inoue K (2005) Regulation of cell-to-cell communication mediated by astrocytic ATP in the CNS. Purinergic Signalling 1:211–217

    PubMed  CAS  Google Scholar 

  168. Neary JT, Rathbone MP, Cattabeni F, Abbracchio MP, Burnstock G (1996) Trophic actions of extracellular nucleotides and nucleosides on glial and neuronal cells. Trends Neurosci 19:13–18

    PubMed  CAS  Google Scholar 

  169. Ciccarelli R, Ballerini P, Sabatino G, Rathbone MP, D’Onofrio M, Caciagli F, Di Iorio P (2001) Involvement of astrocytes in purine-mediated reparative processes in the brain. Int J Dev Neurosci 19:395–414

    PubMed  CAS  Google Scholar 

  170. Brambilla R, Burnstock G, Bonazzi A, Ceruti S, Cattabeni F, Abbracchio MP (1999) Cyclooxygenase-2 mediates P2Y receptor-induced reactive astrogliosis. Br J Pharmacol 126:563–567

    PubMed  CAS  Google Scholar 

  171. Brambilla R, Neary JT, Cattabeni F, Cottini L, D’Ippolito G, Schiller PC, Abbracchio MP (2002) Induction of COX-2 and reactive gliosis by P2Y receptors in rat cortical astrocytes is dependent on ERK1/2 but independent of calcium signalling. J Neurochem 83:1285–1296

    PubMed  CAS  Google Scholar 

  172. Delicado EG, Jimenez AI, Carrasquero LM, Castro E, Miras-Portugal MT (2005) Cross-talk among epidermal growth factor, Ap5A, and nucleotide receptors causing enhanced ATP Ca2+ signaling involves extracellular kinase activation in cerebellar astrocytes. J Neurosci Res 81:789–796

    PubMed  CAS  Google Scholar 

  173. Planas AM, Justicia C, Soriano MA, Ferrer I (1998) Epidermal growth factor receptor in proliferating reactive glia following transient focal ischemia in the rat brain. Glia 23:120–129

    PubMed  CAS  Google Scholar 

  174. Fumagalli M, Brambilla R, D’Ambrosi N, Volonte C, Matteoli M, Verderio C, Abbracchio MP (2003) Nucleotide-mediated calcium signaling in rat cortical astrocytes: Role of P2X and P2Y receptors. Glia 43:203–218

    Google Scholar 

  175. Jacques-Silva MC, Rodnight R, Lenz G, Liao Z, Kong Q, Tran M, Kang Y, Gonzalez FA, Weisman GA, Neary JT (2004) P2X7 receptors stimulate AKT phosphorylation in astrocytes. Br J Pharmacol 141:1106–1117

    PubMed  CAS  Google Scholar 

  176. Koizumi S, Inoue K (2004) Regulation by astrocytic ATP of synaptic transmission. Nippon Yakurigaku Zasshi 123:389–396

    PubMed  CAS  Google Scholar 

  177. Shinozaki Y, Koizumi S, Ishida S, Sawada J, Ohno Y, Inoue K (2005) Cytoprotection against oxidative stress-induced damage of astrocytes by extracellular ATP via P2Y1 receptors. Glia 49:288–300

    PubMed  Google Scholar 

  178. Gendron FP, Newbold NL, Vivas-Mejia PE, Wang M, Neary JT, Sun GY, Gonzalez FA, Weisman GA (2003) Signal transduction pathways for P2Y2 and P2X7 nucleotide receptors that mediate neuroinflammatory responses in astrocytes and microglial cells. Biomed Res 14:47–61

    CAS  Google Scholar 

  179. Chen WC, Chen CC (1998) ATP-induced arachidonic acid release in cultured astrocytes is mediated by Gi protein coupled P2Y1 and P2Y2 receptors. Glia 22:360–370

    PubMed  CAS  Google Scholar 

  180. Kim SG, Soltysiak KA, Gao ZG, Chang TS, Chung E, Jacobson KA (2003) Tumor necrosis factor alpha-induced apoptosis in astrocytes is prevented by the activation of P2Y6, but not P2Y4 nucleotide receptors. Biochem Pharmacol 65:923–931

    PubMed  CAS  Google Scholar 

  181. Narcisse L, Scemes E, Zhao Y, Lee SC, Brosnan CF (2005) The cytokine IL-1beta transiently enhances P2X7 receptor expression and function in human astrocytes. Glia 49:245–258

    PubMed  Google Scholar 

  182. Ballerini P, Ciccarelli R, Caciagli F, Rathbone MP, Werstiuk ES, Traversa U, Buccella S, Giuliani P, Jang S, Nargi E, Visini D, Santavenere C, Di Iorio P (2005) P2X7 receptor activation in rat brain cultured astrocytes increases the biosynthetic release of cysteinyl leukotrienes. Int J Immunopathol Pharmacol 18:417–430

    PubMed  CAS  Google Scholar 

  183. Neary JT, Kang Y, Willoughby KA, Ellis EF (2003) Activation of extracellular signal-regulated kinase by stretch-induced injury in astrocytes involves extracellular ATP and P2 purinergic receptors. J Neurosci 23:2348–2356

    PubMed  CAS  Google Scholar 

  184. Neary JT, Kang Y, Tran M, Feld J (2005) Traumatic injury activates protein kinase B/Akt in cultured astrocytes: role of extracellular ATP and P2 purinergic receptors. J Neurotrauma 22:491–500

    PubMed  Google Scholar 

  185. Hindley S, Herman MA, Rathbone MP (1994) Stimulation of reactive astrogliosis in vivo by extracellular adenosine diphosphate or an adenosine A2 receptor agonist. J Neurosci Res 38:399–406

    PubMed  CAS  Google Scholar 

  186. Franke H, Krügel U, Illes P (1999) P2 receptor-mediated proliferative effects on astrocytes in vivo. Glia 28:190–200

    PubMed  CAS  Google Scholar 

  187. Franke H, Krügel U, Schmidt R, Grosche J, Reichenbach A, Illes P (2001) P2 receptor-types involved in astrogliosis in vivo. Br J Pharmacol 134:1180–1189

    PubMed  CAS  Google Scholar 

  188. Franke H, Krügel U, Grosche J, Heine C, Härtig W, Allgaier C, Illes P (2004) P2Y receptor expression on astrocytes in the nucleus accumbens of rats. Neuroscience 127:431–441

    PubMed  CAS  Google Scholar 

  189. Franke H, Kittner H, Grosche J, Illes P (2003) Enhanced P2Y1 receptor expression in the brain after sensitisation with d-amphetamine. Psychopharmacology (Berl) 167:187–194

    CAS  Google Scholar 

  190. Moore DJ, Murdock PR, Watson JM, Faull RL, Waldvogel HJ, Szekeres PG, Wilson S, Freeman KB, Emson PC (2003) GPR105, a novel Gi/o-coupled UDP-glucose receptor expressed on brain glia and peripheral immune cells, is regulated by immunologic challenge: possible role in neuroimmune function. Brain Res Mol Brain Res 118:10–23

    PubMed  CAS  Google Scholar 

  191. Malenka RC, Bear MF (2004) LTP and LTD: an embarrassment of riches. Neuron 44:5–21

    PubMed  CAS  Google Scholar 

  192. Bear MF, Malenka RC (1994) Synaptic plasticity: LTP and LTD. Curr Opin Neurobiol 4:389–399

    PubMed  CAS  Google Scholar 

  193. Otani S, Blond O, Desce JM, Crepel F (1998) Dopamine facilitates long-term depression of glutamatergic transmission in rat prefrontal cortex. Neuroscience 85:669–676

    PubMed  CAS  Google Scholar 

  194. Nieus T, Sola E, Mapelli J, Saftenku E, Rossi P, D’Angelo E (2006) LTP regulates burst initiation and frequency at mossy fiber-granule cell synapses of rat cerebellum: experimental observations and theoretical predictions. J Neurophysiol 95:686–699

    PubMed  Google Scholar 

  195. Picconi B, Pisani A, Barone I, Bonsi P, Centonze D, Bernardi G, Calabresi P (2005) Pathological synaptic plasticity in the striatum: implications for Parkinson’s disease. Neurotoxicology 26:779–783

    PubMed  CAS  Google Scholar 

  196. Dityatev AE, Bolshakov VY (2005) Amygdala, long-term potentiation, and fear conditioning. Neuroscientist 11:75–88

    PubMed  CAS  Google Scholar 

  197. Herrero JF, Laird JM, Lopez-Garcia JA (2000) Wind-up of spinal cord neurones and pain sensation: much ado about something? Prog Neurobiol 61:169–203

    PubMed  CAS  Google Scholar 

  198. Wieraszko A, Ehrlich YH (1994) On the role of extracellular ATP in the induction of long-term potentiation in the hippocampus. J Neurochem 63:1731–1738

    Article  PubMed  CAS  Google Scholar 

  199. Chen W, Wieraszko A, Hogan MV, Yang HA, Kornecki E, Ehrlich YH (1996) Surface protein phosphorylation by ecto-protein kinase is required for the maintenance of hippocampal long-term potentiation. Proc Natl Acad Sci USA 93:8688–8693

    PubMed  CAS  Google Scholar 

  200. Fujii S, Kato H, Furuse H, Ito K, Osada H, Hamaguchi T, Kuroda Y (1995) The mechanism of ATP-induced long-term potentiation involves extracellular phosphorylation of membrane proteins in guinea-pig hippocampal CA1 neurons. Neurosci Lett 187:130–132

    PubMed  CAS  Google Scholar 

  201. Fujii S, Kuroda Y, Ito K, Kato H (2000) Long-term potentiation induction—a synaptic catch mechanism released by extracellular phosphorylation. Neuroscience 96:259–266

    PubMed  CAS  Google Scholar 

  202. Wirkner K, Stanchev D, Koles L, Klebingat M, Dihazi H, Flehmig G, Vial C, Evans RJ, Fürst S, Mager PP, Eschrich K, Illes P (2005) Regulation of human recombinant P2X3 receptors by ecto-protein kinase C. J Neurosci 25:7734–7742

    PubMed  CAS  Google Scholar 

  203. Stanchev D, Flehmig G, Gerevich Z, Nörenberg W, Dihazi H, Fürst S, Eschrich K, Illes P, Wirkner K (2006) Decrease of current responses at human recombinant P2X3 receptors after substitution by Asp of Ser/Thr residues in protein kinase C phosphorylation sites of their ecto-domains. Neurosci Lett 393:78–83

    PubMed  CAS  Google Scholar 

  204. Wang Y, Haughey NJ, Mattson MP, Furukawa K (2004) Dual effects of ATP on rat hippocampal synaptic plasticity. Neuroreport 15:633–636

    PubMed  CAS  Google Scholar 

  205. da Silva BM, de Mendonca A, Ribeiro JA (2005) Long-term depression is not modulated by ATP receptors in the rat CA1 hippocampal region. Neurosci Lett 383:345–349

    PubMed  Google Scholar 

  206. Wirkner K, Köles L, Thümmler S, Luthardt J, Poelchen W, Franke H, Fürst S, Illes P (2002) Interaction between P2Y and NMDA receptors in layer V pyramidal neurons of the rat prefrontal cortex. Neuropharmacology 42:476–488

    PubMed  CAS  Google Scholar 

  207. Guzman SJ, Gerevich Z, Hengstler JG, Illes P, Kleemann W (2005) P2Y1 receptors inhibit both strength and plasticity of glutamatergic synaptic neurotransmission in the rat prefrontal cortex. Synapse 57:235–238

    PubMed  CAS  Google Scholar 

  208. Hasko G, Pacher P, Vizi ES, Illes P (2005) Adenosine receptor signaling in the brain immune system. Trends Pharmacol Sci 26:511–516

    PubMed  CAS  Google Scholar 

  209. Almeida T, Rodrigues RJ, de Mendonca A, Ribeiro JA, Cunha RA (2003) Purinergic P2 receptors trigger adenosine release leading to adenosine A2A receptor activation and facilitation of long-term potentiation in rat hippocampal slices. Neuroscience 122:111–121

    PubMed  CAS  Google Scholar 

  210. Calabresi P, Saulle E, Centonze D, Pisani A, Marfia GA, Bernardi G (2002) Post-ischaemic long-term synaptic potentiation in the striatum: a putative mechanism for cell type-specific vulnerability. Brain 125:844–860

    PubMed  Google Scholar 

  211. Zhang Y, Deng P, Li Y, Xu ZC (2005) Enhancement of excitatory synaptic transmission in spiny neurons after transient forebrain ischemia. J Neurophysiol 95:1537–1544

    PubMed  Google Scholar 

  212. Gysbers JW, Rathbone MP (1992) Guanosine enhances NGF-stimulated neurite outgrowth in PC12 cells. Neuroreport 3:997–1000

    PubMed  CAS  Google Scholar 

  213. Heilbronn A, Maienschein V, Carstensen K, Gann W, Zimmermann H (1995) Crucial role of ecto-5′-nucleotidase in differentiation and survival of developing neural cells. Neuroreport 7:257–261

    PubMed  CAS  Google Scholar 

  214. Gysbers JW, Rathbone MP (1996) GTP and guanosine synergistically enhance NGF-induced neurite outgrowth from PC12 cells. Int J Dev Neurosci 14:19–34

    PubMed  CAS  Google Scholar 

  215. Höpker VH, Saffrey MJ, Burnstock G (1996) Neurite outgrowth of striatal neurons in vitro: involvement of purines in the growth-promoting effect of myenteric plexus explants. Int J Dev Neurosci 14:439–451

    PubMed  Google Scholar 

  216. Benowitz LI, Jing Y, Tabibiazar R, Jo SA, Petrausch B, Stuermer CA, Rosenberg PA, Irwin N (1998) Axon outgrowth is regulated by an intracellular purine-sensitive mechanism in retinal ganglion cells. J Biol Chem 273:29626–29634

    PubMed  CAS  Google Scholar 

  217. Aono K, Nakanishi N, Yamada S (1990) Increase in intracellular Ca2+ level and modulation of nerve growth factor action on pheochromocytoma PC12h cells by extracellular ATP. Meikai Daigaku Shigaku Zasshi 19:221–229

    PubMed  CAS  Google Scholar 

  218. Huang CM, Kao LS (1996) Nerve growth factor, epidermal growth factor, and insulin differentially potentiate ATP-induced [Ca2+]i rise and dopamine secretion in PC12 cells. J Neurochem 66:124–130

    Article  PubMed  CAS  Google Scholar 

  219. Gysbers JW, Guarnieri S, Mariggio MA, Pietrangelo T, Fano G, Rathbone MP (2000) Extracellular guanosine 5′ triphosphate enhances nerve growth factor-induced neurite outgrowth via increases in intracellular calcium. Neuroscience 96:817–824

    PubMed  CAS  Google Scholar 

  220. Pooler AM, Guez DH, Benedictus R, Wurtman RJ (2005) Uridine enhances neurite outgrowth in nerve growth factor-differentiated PC12. Neuroscience 134:207–214

    PubMed  CAS  Google Scholar 

  221. Chorna NE, Santiago-Perez LI, Erb L, Seye CI, Neary JT, Sun GY, Weisman GA, Gonzalez FA (2004) P2Y receptors activate neuroprotective mechanisms in astrocytic cells. J Neurochem 91:119–132

    PubMed  CAS  Google Scholar 

  222. Heine C, Heimrich B, Vogt J, Wegner A, Illes P, Franke H (2006) P2 receptor-stimulation influences axonal outgrowth in the developing hippocampus in vitro. Neuroscience 138:303–311

    PubMed  CAS  Google Scholar 

  223. Abbracchio MP, Ceruti S, Bolego C, Puglisi L, Burnstock G, Cattabeni F (1996) Trophic roles of P2 purinoceptors in central nervous system astroglial cells. Ciba Found Symp 198:142–147

    PubMed  CAS  Google Scholar 

  224. Di Virgilio F, Chiozzi P, Falzoni S, Ferrari D, Sanz JM, Venketaraman V, Baricordi OR (1998) Cytolytic P2X purinoceptors. Cell Death Differ 5:191–199

    PubMed  Google Scholar 

  225. Neary JT (1996) Trophic actions of extracellular ATP on astrocytes, synergistic interactions with fibroblast growth factors and underlying signal transduction mechanisms. Ciba Found Symp 198:130–139

    PubMed  CAS  Google Scholar 

  226. Ferrari D, Chiozzi P, Falzoni S, Dal Susino M, Melchiorri L, Baricordi OR, Di Virgilio F (1997) Extracellular ATP triggers IL-1 beta release by activating the purinergic P2Z receptor of human macrophages. J Immunol 159:1451–1458

    PubMed  CAS  Google Scholar 

  227. Ferrari D, Los M, Bauer MK, Vandenabeele P, Wesselborg S, Schulze-Osthoff K (1999) P2Z purinoreceptor ligation induces activation of caspases with distinct roles in apoptotic and necrotic alterations of cell death. FEBS Lett 447:71–75

    PubMed  CAS  Google Scholar 

  228. Inoue K (2002) Microglial activation by purines and pyrimidines. Glia 40:156–163

    PubMed  Google Scholar 

  229. Di Virgilio F (2005) Purinergic mechanisms in the immune system: a signal of danger for dendritic cells. Purinergic Signalling 1:205–209

    PubMed  Google Scholar 

  230. Buday PV, Carr CJ, Myga TS (1961) A pharmacologic study of some nucleosides and nucleotides. J Pharm Pharmacol 13:290–299

    CAS  Google Scholar 

  231. Knutsen LJ, Murray TF (1997) Adenosine and ATP in epilepsy. In: Jacobson KA, Jarvis MF (eds) Purinergic approaches in experimental therapeutics. Wiley-Liss, pp 423–447

    Google Scholar 

  232. Kang TC, An SJ, Park SK, Hwang IK, Won MH (2003) P2X2 and P2X4 receptor expression is regulated by a GABAA receptor-mediated mechanism in the gerbil hippocampus. Brain Res Mol Brain Res 116:168–175

    PubMed  CAS  Google Scholar 

  233. Kang TC, Park SK, Hwang IK, An SJ, Won MH (2004) GABAB receptor-mediated regulation of P2X7 receptor expression in the gerbil hippocampus. Brain Res Mol Brain Res 121:12–18

    PubMed  CAS  Google Scholar 

  234. Vianna EP, Ferreira AT, Naffah-Mazzacoratti MG, Sanabria ER, Funke M, Cavalheiro EA, Fernandes MJ (2002) Evidence that ATP participates in the pathophysiology of pilocarpine-induced temporal lobe epilepsy: fluorimetric, immunohistochemical, and Western blot studies. Epilepsia 43(Suppl 5):227–229

    PubMed  CAS  Google Scholar 

  235. Stoeckel ME, Uhl-Bronner S, Hugel S, Veinante P, Klein MJ, Mutterer J, Freund-Mercier MJ, Schlichter R (2003) Cerebrospinal fluid-contacting neurons in the rat spinal cord, a gamma-aminobutyric acidergic system expressing the P2X2 subunit of purinergic receptors, PSA-NCAM, and GAP-43 immunoreactivities: light and electron microscopic study. J Comp Neurol 457:159–174

    PubMed  Google Scholar 

  236. Haughey NJ, Mattson MP (2003) Alzheimer’s amyloid beta-peptide enhances ATP/gap junction-mediated calcium-wave propagation in astrocytes. Neuromolecular Med 3:173–180

    PubMed  Google Scholar 

  237. Parvathenani LK, Tertyshnikova S, Greco CR, Roberts SB, Robertson B, Posmantur R (2003) P2X7 mediates superoxide production in primary microglia and is up-regulated in a transgenic mouse model of Alzheimer’s disease. J Biol Chem 278:13309–13317

    PubMed  CAS  Google Scholar 

  238. Bringmann A, Pannicke T, Uhlmann S, Kohen L, Wiedemann P, Reichenbach A (2002) Membrane conductance of Müller glial cells in proliferative diabetic retinopathy. Can J Ophthalmol 37:221–227

    PubMed  Google Scholar 

  239. Moore D, Chambers J, Waldvogel H, Faull R, Emson P (2000) Regional and cellular distribution of the P2Y1 purinergic receptor in the human brain: striking neuronal localisation. J Comp Neurol 421:374–384

    PubMed  CAS  Google Scholar 

  240. Moore D, Iritani S, Chambers J, Emson P (2000) Immunohistochemical localization of the P2Y1 purinergic receptor in Alzheimer’s disease. Neuroreport 11:3799–3803

    PubMed  CAS  Google Scholar 

  241. Krügel U, Kittner H, Franke H, Illes P (2001) Stimulation of P2 receptors in the ventral tegmental area enhances dopaminergic mechanisms in vivo. Neuropharmacology 40:1084–1093

    PubMed  Google Scholar 

  242. Kittner H, Krügel U, Illes P (2001) The purinergic P2 receptor antagonist pyridoxalphosphate-6-azophenyl-2′4′-disulphonic acid prevents both the acute locomotor effects of amphetamine and the behavioural sensitization caused by repeated amphetamine injections in rats. Neuroscience 102:241–243

    PubMed  CAS  Google Scholar 

  243. Gerevich Z, Illes P (2004) P2Y receptors and pain transmission. Purinergic Signalling 1:3–10

    PubMed  CAS  Google Scholar 

  244. Gerevich Z, Borvendeg SJ, Schröder W, Franke H, Wirkner K, Nörenberg W, Fürst S, Gillen C, Illes P (2004) Inhibition of N-type voltage-activated calcium channels in rat dorsal root ganglion neurons by P2Y receptors is a possible mechanism of ADP-induced analgesia. J Neurosci 24:797–807

    PubMed  CAS  Google Scholar 

  245. Li C, Aguayo L, Peoples RW, Weight FF (1993) Ethanol inhibits a neuronal ATP-gated ion channel. Mol Pharmacol 44:871–875

    PubMed  CAS  Google Scholar 

  246. Weight FF, Li C, Peoples RW (1999) Alcohol action on membrane ion channels gated by extracellular ATP (P2X receptors). Neurochem Int 35:143–152

    PubMed  CAS  Google Scholar 

  247. Li C, Xiong K, Weight FF (2000) Ethanol inhibition of adenosine 5′-triphosphate-activated current in freshly isolated adult rat hippocampal CA1 neurons. Neurosci Lett 295:77–80

    PubMed  CAS  Google Scholar 

  248. Xiong K, Li C, Weight FF (2000) Inhibition by ethanol of rat P2X4 receptors expressed in Xenopus oocytes. Br J Pharmacol 130:1394–1398

    PubMed  CAS  Google Scholar 

  249. Davies DL, Kochegarov AA, Kuo ST, Kulkarni AA, Woodward JJ, King BF, Alkana RL (2005) Ethanol differentially affects ATP-gated P2X3 and P2X4 receptor subtypes expressed in Xenopus oocytes. Neuropharmacology 49:243–253

    PubMed  CAS  Google Scholar 

  250. Davies DL, Machu TK, Guo Y, Alkana RL (2002) Ethanol sensitivity in ATP-gated P2X receptors is subunit dependent. Alcohol Clin Exp Res 26:773–778

    PubMed  CAS  Google Scholar 

  251. Phillis JW, O’Regan MH, Perkins LM (1993) Adenosine 5′-triphosphate release from the normoxic and hypoxic in vivo rat cerebral cortex. Neurosci Lett 151:94–96

    PubMed  CAS  Google Scholar 

  252. Juranyi Z, Sperlagh B, Vizi ES (1999) Involvement of P2 purinoceptors and the nitric oxide pathway in [3H]purine outflow evoked by short-term hypoxia and hypoglycemia in rat hippocampal slices. Brain Res 823:183–190

    PubMed  CAS  Google Scholar 

  253. Collo G, Neidhart S, Kawashima E, Kosco-Vilbois M, North RA, Buell G (1997) Tissue distribution of the P2X7 receptor. Neuropharmacology 36:1277–1283

    PubMed  CAS  Google Scholar 

  254. Cavaliere F, Florenzano F, Amadio S, Fusco FR, Viscomi MT, D’Ambrosi N, Vacca F, Sancesario G, Bernardi G, Molinari M, Volonte C (2003) Up-regulation of P2X2, P2X4 receptor and ischemic cell death: prevention by P2 antagonists. Neuroscience 120:85–98

    PubMed  CAS  Google Scholar 

  255. Cavaliere F, Amadio S, Sancesario G, Bernardi G, Volonte C (2004) Synaptic P2X7 and oxygen/glucose deprivation in organotypic hippocampal cultures. J Cereb Blood Flow Metab 24:392–398

    PubMed  CAS  Google Scholar 

  256. Franke H, Günther A, Grosche J, Schmidt R, Rossner S, Reinhardt R, Faber-Zuschratter H, Schneider D, Illes P (2004) P2X7 receptor expression after ischemia in the cerebral cortex of rats. J Neuropathol Exp Neurol 63:686–699

    PubMed  CAS  Google Scholar 

  257. Melani A, Amadio S, Gianfriddo M, Vannucchi MG, Volonte C, Bernardi G, Pedata F, Sancesario G (2006) P2X7 receptor modulation on microglial cells and reduction of brain infarct caused by middle cerebral artery occlusion in rat. J Cereb Blood Flow Metab (in press)

  258. Cavaliere F, Sancesario G, Bernardi G, Volonte C (2002) Extracellular ATP and nerve growth factor intensify hypoglycemia-induced cell death in primary neurons: role of P2 and NGFRp75 receptors. J Neurochem 83:1129–1138

    PubMed  CAS  Google Scholar 

  259. Wirkner K, Kofalvi A, Fischer W, Günther A, Franke H, Gröger-Arndt H, Nörenberg W, Madarasz E, Vizi ES, Schneider D, Sperlagh B, Illes P (2005) Supersensitivity of P2X receptors in cerebrocortical cell cultures after in vitro ischemia. J Neurochem 95:1421–1437

    PubMed  CAS  Google Scholar 

  260. Surprenant A, Rassendren F, Kawashima E, North RA, Buell G (1996) The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 272:735–738

    PubMed  CAS  Google Scholar 

  261. Di Virgilio F, Sanz JM, Chiozzi P, Falzoni S (1999) The P2Z/P2X7 receptor of microglial cells: a novel immunomodulatory receptor. Prog Brain Res 120:355–368

    Article  PubMed  Google Scholar 

  262. Virginio C, MacKenzie A, Rassendren FA, North RA, Surprenant A (1999) Pore dilation of neuronal P2X receptor channels. Nat Neurosci 2:315–321

    PubMed  CAS  Google Scholar 

  263. Gu BJ, Zhang WY, Bendall LJ, Chessell IP, Buell GN, Wiley JS (2000) Expression of P2X7 purinoceptors on human lymphocytes and monocytes: evidence for nonfunctional P2X7 receptors. Am J Physiol Cell Physiol 279:C1189–C1197

    PubMed  CAS  Google Scholar 

  264. Pubill D, Dayanithi G, Siatka C, Andres M, Dufour MN, Guillon G, Mendre C (2001) ATP induces intracellular calcium increases and actin cytoskeleton disaggregation via P2X receptors. Cell Calcium 29:299–309

    PubMed  CAS  Google Scholar 

  265. Kim M, Jiang LH, Wilson HL, North RA, Surprenant A (2001) Proteomic and functional evidence for a P2X7 receptor signalling complex. EMBO J 20:6347–6358

    PubMed  CAS  Google Scholar 

  266. Armstrong JN, Brust TB, Lewis RG, MacVicar BA (2002) Activation of presynaptic P2X7-like receptors depresses mossy fiber-CA3 synaptic transmission through p38 mitogen-activated protein kinase. J Neurosci 22:5938–5945

    PubMed  CAS  Google Scholar 

  267. Atkinson L, Milligan CJ, Buckley NJ, Deuchars J (2002) An ATP-gated ion channel at the cell nucleus. Nature 420:42

    PubMed  CAS  Google Scholar 

  268. Lundy PM, Hamilton MG, Mi L, Gong W, Vair C, Sawyer TW, Frew R (2002) Stimulation of Ca2+ influx through ATP receptors on rat brain synaptosomes: identification of functional P2X7 receptor subtypes. Br J Pharmacol 135:1616–1626

    PubMed  CAS  Google Scholar 

  269. Sperlagh B, Kofalvi A, Deuchars J, Atkinson L, Milligan CJ, Buckley NJ, Vizi ES (2002) Involvement of P2X7 receptors in the regulation of neurotransmitter release in the rat hippocampus. J Neurochem 81:1196–1211

    PubMed  CAS  Google Scholar 

  270. Ishii K, Kaneda M, Li H, Rockland KS, Hashikawa T (2003) Neuron-specific distribution of P2X7 purinergic receptors in the monkey retina. J Comp Neurol 459:267–277

    PubMed  CAS  Google Scholar 

  271. Allgaier C, Reinhardt R, Schädlich H, Rubini P, Bauer S, Reichenbach A, Illes P (2004) Somatic and axonal effects of ATP via P2X2 but not P2X7 receptors in rat thoracolumbar sympathetic neurones. J Neurochem 90:359–367

    PubMed  CAS  Google Scholar 

  272. Sim JA, Young MT, Sung HY, North RA, Surprenant A (2004) Reanalysis of P2X7 receptor expression in rodent brain. J Neurosci 24:6307–6314

    PubMed  CAS  Google Scholar 

  273. Papp L, Vizi ES, Sperlagh B (2004) Lack of ATP-evoked GABA and glutamate release in the hippocampus of P2X7 receptor−/− mice. Neuroreport 15:2387–2391

    PubMed  CAS  Google Scholar 

  274. Cheewatrakoolpong B, Gilchrest H, Anthes JC, Greenfeder S (2005) Identification and characterization of splice variants of the human P2X7 ATP channel. Biochem Biophys Res Commun 332:17–27

    PubMed  CAS  Google Scholar 

  275. Miras-Portugal MT, Diaz-Hernandez M, Giraldez L, Hervas C, Gomez-Villafuertes R, Sen RP, Gualix J, Pintor J (2003) P2X7 receptors in rat brain: presence in synaptic terminals and granule cells. Neurochem Res 28:1597–1605

    PubMed  CAS  Google Scholar 

  276. Hervas C, Perez-Sen R, Miras-Portugal MT (2005) Presence of diverse functional P2X receptors in rat cerebellar synaptic terminals. Biochem Pharmacol 70:770–785

    PubMed  CAS  Google Scholar 

  277. Sanz JM, Di Virgilio F (2000) Kinetics and mechanism of ATP-dependent IL-1 beta release from microglial cells. J Immunol 164:4893–4898

    PubMed  CAS  Google Scholar 

  278. Le Feuvre RA, Brough D, Touzani O, Rothwell NJ (2003) Role of P2X7 receptors in ischemic and excitotoxic brain injury in vivo. J Cereb Blood Flow Metab 23:381–384

    PubMed  Google Scholar 

  279. Moran-Jimenez MJ, Matute C (2000) Immunohistochemical localization of the P2Y1 purinergic receptor in neurons and glial cells of the central nervous system. Brain Res Mol Brain Res 78:50–58

    PubMed  CAS  Google Scholar 

  280. Lämmer A, Günther A, Kittner H, Franke H, Krügel U, Schneider D, Illes P (2004) In vivo effects of inhibition of P2 receptors after focal cerebral ischemia in the rat. Int J Dev Neurosci 22:587

    Google Scholar 

  281. Florenzano F, Viscomi MT, Cavaliere F, Volonte C, Molinari M (2002) Cerebellar lesion up-regulates P2X1 and P2X2 purinergic receptors in precerebellar nuclei. Neuroscience 115:425–434

    PubMed  CAS  Google Scholar 

  282. Viscomi MT, Florenzano F, Amadio S, Bernardi G, Molinari M (2005) Partial resistance of ataxin-2-containing olivary and pontine neurons to axotomy-induced degeneration. Brain Res Bull 66:212–221

    PubMed  CAS  Google Scholar 

  283. Novakovic SD, Kassotakis LC, Oglesby IB, Smith JA, Eglen RM, Ford AP, Hunter JC (1999) Immunocytochemical localization of P2X3 purinoceptors in sensory neurons in naive rats and following neuropathic injury. Pain 80:273–282

    PubMed  CAS  Google Scholar 

  284. Tsuzuki K, Kondo E, Fukuoka T, Yi D, Tsujino H, Sakagami M, Noguchi K (2001) Differential regulation of P2X3 mRNA expression by peripheral nerve injury in intact and injured neurons in the rat sensory ganglia. Pain 91:351–360

    PubMed  CAS  Google Scholar 

  285. Tsuda M, Shigemoto-Mogami Y, Ueno S, Koizumi S, Ueda H, Iwanaga T, Inoue K (2002) Downregulation of P2X3 receptor-dependent sensory functions in A/J inbred mouse strain. Eur J Neurosci 15:1444–1450

    PubMed  Google Scholar 

  286. Franke H, Grosche J, Schädlich H, Krügel U, Allgaier C, Illes P (2001) P2X receptor expression on astrocytes in the nucleus accumbens of rats. Neuroscience 108:421–429

    PubMed  CAS  Google Scholar 

  287. Franke H, Krügel U, Grosche J, Illes P (2003) Immunoreactivity for glial fibrillary acidic protein and P2 receptor expression on astrocytes in vivo. Drug Dev Res 59:175–189

    CAS  Google Scholar 

  288. Ballerini P, Giulinai P, Buccella S, Nargi E, Santavenere C, Scemes E, Rathbone MP, Caciagli F (2000) P2X7 ATP receptor-mediated modulation of astrocyte proliferation and coupling. Drug Dev Res 50:108

    Google Scholar 

  289. Sun SH, Lin LB, Hung AC, Kuo JS (1999) ATP-stimulated Ca2+ influx and phospholipase D activities of a rat brain-derived type-2 astrocyte cell line, RBA-2, are mediated through P2X7 receptors. J Neurochem 73:334–343

    PubMed  CAS  Google Scholar 

  290. Hung AC, Sun SH (2002) The P2X7 receptor-mediated phospholipase D activation is regulated by both PKC-dependent and PKC-independent pathways in a rat brain-derived Type-2 astrocyte cell line, RBA-2. Cell Signal 14:83–92

    PubMed  CAS  Google Scholar 

  291. Panenka W, Jijon H, Herx LM, Armstrong JN, Feighan D, Wei T, Yong VW, Ransohoff RM, MacVicar BA (2001) P2X7-like receptor activation in astrocytes increases chemokine monocyte chemoattractant protein-1 expression via mitogen-activated protein kinase. J Neurosci 21:7135–7142

    PubMed  CAS  Google Scholar 

  292. Gendron FP, Neary JT, Theiss PM, Sun GY, Gonzalez FA, Weisman GA (2003) Mechanisms of P2X7 receptor-mediated ERK1/2 phosphorylation in human astrocytoma cells. Am J Physiol Cell Physiol 284:C571–C581

    PubMed  CAS  Google Scholar 

  293. Erlinge D, You J, Wahlestedt C, Edvinsson L (1995) Characterisation of an ATP receptor mediating mitogenesis in vascular smooth muscle cells. Eur J Pharmacol 289:135–149

    PubMed  CAS  Google Scholar 

  294. Araque A, Parpura V, Sanzgiri RP, Haydon PG (1999) Tripartite synapses: glia, the unacknowledged partner. Trends Neurosci 22:208–215

    PubMed  CAS  Google Scholar 

  295. Anderson C, Duan S, Chen Y, Keung E, Swanson R (2000) ATP-activated glutamate release through non-selective P2Z/P2X7 like channels in cultured mouse astrocytes. Drug Dev Res 50:92

    Google Scholar 

  296. Ballerini P, Rathbone MP, Di Iorio P, Renzetti A, Giuliani P, D’Alimonte I, Trubiani O, Caciagli F, Ciccarelli R (1996) Rat astroglial P2Z (P2X7) receptors regulate intracellular calcium and purine release. Neuroreport 7:2533–2537

    PubMed  CAS  Google Scholar 

  297. Wang CM, Chang YY, Kuo JS, Sun SH (2002) Activation of P2X7 receptors induced [3H]GABA release from the RBA-2 type-2 astrocyte cell line through a Cl−/HCO3-dependent mechanism. Glia 37:8–18

    PubMed  Google Scholar 

  298. Schilling M, Besselmann M, Leonhard C, Mueller M, Ringelstein EB, Kiefer R (2003) Microglial activation precedes and predominates over macrophage infiltration in transient focal cerebral ischemia: a study in green fluorescent protein transgenic bone marrow chimeric mice. Exp Neurol 183:25–33

    PubMed  Google Scholar 

  299. Günther A, Küppers-Tiedt L, Schneider PM, Kunert I, Berrouschot J, Schneider D, Rossner S (2005) Reduced infarct volume and differential effects on glial cell activation after hyperbaric oxygen treatment in rat permanent focal cerebral ischaemia. Eur J Neurosci 21:3189–3194

    PubMed  Google Scholar 

  300. Giulian D (1993) Reactive glia as rivals in regulating neuronal survival. Glia 7:102–110

    PubMed  CAS  Google Scholar 

  301. Stoll G, Jander S, Schroeter M (2000) Cytokines in CNS disorders: neurotoxicity versus neuroprotection. J Neural Transm Suppl 59:81–89

    PubMed  CAS  Google Scholar 

  302. Cavaliere F, Dinkel K, Reymann K (2005) Microglia response and P2 receptor participation in oxygen/glucose deprivation-induced cortical damage. Neuroscience 136:615–623

    PubMed  CAS  Google Scholar 

  303. Ferrari D, Villalba M, Chiozzi P, Falzoni S, Ricciardi-Castagnoli P, Di Virgilio F (1996) Mouse microglial cells express a plasma membrane pore gated by extracellular ATP. J Immunol 156:1531–1539

    PubMed  CAS  Google Scholar 

  304. Ferrari D, Chiozzi P, Falzoni S, Hanau S, Di Virgilio F (1997) Purinergic modulation of interleukin-1β release from microglial cells stimulated with bacterial endotoxin. J Exp Med 185:579–582

    PubMed  CAS  Google Scholar 

  305. Hide I, Tanaka M, Inoue A, Nakajima K, Kohsaka S, Inoue K, Nakata Y (2000) Extracellular ATP triggers tumor necrosis factor-alpha release from rat microglia. J Neurochem 75:965–972

    PubMed  CAS  Google Scholar 

  306. Nedergaard M, Ransom B, Goldman SA (2003) New roles for astrocytes: redefining the functional architecture of the brain. Trends Neurosci 26:523–530

    PubMed  CAS  Google Scholar 

  307. Streit WJ, Conde JR, Fendrick SE, Flanary BE, Mariani CL (2005) Role of microglia in the central nervous system’s immune response. Neurol Res 27:685–691

    PubMed  Google Scholar 

  308. Streit WJ, Mrak RE, Griffin WS (2004) Microglia and neuroinflammation: a pathological perspective. J Neuroinflamm 1:14–18

    Google Scholar 

  309. Vilhardt F (2005) Microglia: phagocyte and glia cell. Int J Biochem Cell Biol 37:17–21

    PubMed  CAS  Google Scholar 

  310. Xiang Z, Chen M, Ping J, Dunn P, Lv J, Jiao B, Burnstock G (2006) Microglial morphology and its transformation after challenge by extracellular ATP in vitro. J Neurosci Res 83:91–101

    PubMed  CAS  Google Scholar 

  311. Davalos D, Grutzendler J, Yang G, Kim JV, Zuo Y, Jung S, Littman DR, Dustin ML, Gan WB (2005) ATP mediates rapid microglial response to local brain injury in vivo. Nat Neurosci 8:752–758

    PubMed  CAS  Google Scholar 

  312. Xiang Z, Burnstock G (2005) Expression of P2X receptors on rat microglial cells during early development. Glia 52:119–126

    PubMed  Google Scholar 

  313. Boucsein C, Zacharias R, Farber K, Pavlovic S, Hanisch UK, Kettenmann H (2003) Purinergic receptors on microglial cells: functional expression in acute brain slices and modulation of microglial activation in vitro. Eur J Neurosci 17:2267–2276

    PubMed  Google Scholar 

  314. Sasaki Y, Hoshi M, Akazawa C, Nakamura Y, Tsuzuki H, Inoue K, Kohsaka S (2003) Selective expression of Gi/o-coupled ATP receptor P2Y12 in microglia in rat brain. Glia 44:242–250

    PubMed  Google Scholar 

  315. Bianco F, Fumagalli M, Pravettoni E, D’Ambrosi N, Volonte C, Matteoli M, Abbracchio MP, Verderio C (2005) Pathophysiological roles of extracellular nucleotides in glial cells: differential expression of purinergic receptors in resting and activated microglia. Brain Res Brain Res Rev 48:144–156

    PubMed  CAS  Google Scholar 

  316. Ferrari D, Wesselborg S, Bauer MK, Schulze-Osthoff K (1997) Extracellular ATP activates transcription factor NF-kappa B through the P2Z purinoreceptor by selectively targeting NF-kappa B p65. J Cell Biol 139:1635–1643

    PubMed  CAS  Google Scholar 

  317. Dhawan P, Richmond A (2002) A novel NF-kappa B-inducing kinase-MAPK signaling pathway up-regulates NF-kappa B activity in melanoma cells. J Biol Chem 277:7920–7928

    PubMed  CAS  Google Scholar 

  318. Humphreys BD, Rice J, Kertesy SB, Dubyak GR (2000) Stress-activated protein kinase/JNK activation and apoptotic induction by the macrophage P2X7 nucleotide receptor. J Biol Chem 275:26792–26798

    PubMed  CAS  Google Scholar 

  319. Shigemoto-Mogami Y, Koizumi S, Tsuda M, Ohsawa K, Kohsaka S, Inoue K (2001) Mechanisms underlying extracellular ATP-evoked interleukin-6 release in mouse microglial cell line, MG-5. J Neurochem 78:1339–1349

    PubMed  CAS  Google Scholar 

  320. Inoue K, Nakajima K, Morimoto T, Kikuchi Y, Koizumi S, Illes P, Kohsaka S (1998) ATP stimulation of Ca2+-dependent plasminogen release from cultured microglia. Br J Pharmacol 123:1304–1310

    PubMed  CAS  Google Scholar 

  321. Ohtani Y, Minami M, Satoh M (2000) Expression of inducible nitric oxide synthase mRNA and production of nitric oxide are induced by adenosine triphosphate in cultured rat microglia. Neurosci Lett 293:72–74

    PubMed  CAS  Google Scholar 

  322. Adinolfi E, Pittirani C, Idzko M, Panther E, Norgauer J, Di Virgilio F, Ferrari, D (2005) P2X7 receptor: death or life? Purinergic Signalling 1:219–227

    PubMed  CAS  Google Scholar 

  323. Fujita N, Kakimi M, Ikeda Y, Hiramoto T, Suzuki K (2000) Extracellular ATP inhibits starvation-induced apoptosis via P2X2 receptors in differentiated rat pheochromocytoma PC12 cells. Life Sci 66:1849–1859

    PubMed  CAS  Google Scholar 

  324. Morelli A, Chiozzi P, Chiesa A, Ferrari D, Sanz JM, Falzoni S, Pinton P, Rizzuto R, Olson MF, Di Virgilio F (2003) Extracellular ATP causes ROCK I-dependent bleb formation in P2X7-transfected HEK293 cells. Mol Biol Cell 14:2655–2664

    PubMed  CAS  Google Scholar 

  325. Schulze-Lohoff E, Hugo C, Rost S, Arnold S, Gruber A, Brune B, Sterzel RB (1998) Extracellular ATP causes apoptosis and necrosis of cultured mesangial cells via P2Z/P2X7 receptors. Am J Physiol 275:F962–F971

    PubMed  CAS  Google Scholar 

  326. Wang CM, Chang YY, Sun SH (2003) Activation of P2X7 purinoceptor-stimulated TGF-beta 1 mRNA expression involves PKC/MAPK signalling pathway in a rat brain-derived type-2 astrocyte cell line, RBA-2. Cell Signal 15:1129–1137

    PubMed  Google Scholar 

  327. Hung AC, Chu YJ, Lin YH, Weng JY, Chen HB, Au YC, Sun SH (2005) Roles of protein kinase C in regulation of P2X7 receptor-mediated calcium signalling of cultured type-2 astrocyte cell line, RBA-2. Cell Signal 17:1384–1396

    PubMed  CAS  Google Scholar 

  328. Sellers LA, Simon J, Lundahl TS, Cousens DJ, Humphrey PP, Barnard EA (2001) Adenosine nucleotides acting at the human P2Y1 receptor stimulate mitogen-activated protein kinases and induce apoptosis. J Biol Chem 276:16379–16390

    PubMed  CAS  Google Scholar 

  329. Wang Y, Chang CF, Morales M, Chiang YH, Harvey BK, Su TP, Tsao LI, Chen S, Thiemermann C (2003) Diadenosine tetraphosphate protects against injuries induced by ischemia and 6-hydroxydopamine in rat brain. J Neurosci 23:7958–7965

    PubMed  CAS  Google Scholar 

  330. Volonte C, Merlo D (1996) Selected P2 purinoceptor modulators prevent glutamate-evoked cytotoxicity in cultured cerebellar granule neurons. J Neurosci Res 45:183–193

    PubMed  CAS  Google Scholar 

  331. Volonte C, Ciotti MT, D’Ambrosi N, Lockhart B, Spedding M (1999) Neuroprotective effects of modulators of P2 receptors in primary culture of CNS neurones. Neuropharmacology 38:1335–1342

    PubMed  CAS  Google Scholar 

  332. Yamakuni H, Kawaguchi N, Ohtani Y, Nakamura J, Katayama T, Nakagawa T, Minami M, Satoh M (2002) ATP induces leukemia inhibitory factor mRNA in cultured rat astrocytes. J Neuroimmunol 129:43–50

    PubMed  CAS  Google Scholar 

  333. Amadio S, D’Ambrosi N, Trincavelli ML, Tuscano D, Sancesario G, Bernadi G, Martini C, Volonte C (2005) Differences in the neurotoxicity profile induced by ATP and ATPgammaS in cultured cerebellar granule neurons. Neurochem Int 47:334–342

    PubMed  CAS  Google Scholar 

  334. Buell G, Chessell IP, Michel AD, Collo G, Salazzo M, Herren S, Gretener D, Grahames C, Kaur R, Kosco-Vilbois MH, Humphrey PP (1998) Blockade of human P2X7 receptor function with a monoclonal antibody. Blood 92:3521–3528

    PubMed  CAS  Google Scholar 

  335. Chessell IP, Grahames CBA, Michel AD, Humphrey PPA (2001) Dynamics of P2X7 receptor pore dilation: pharmacological and functional consequences. Drug Dev Res 53:60–65

    CAS  Google Scholar 

  336. Kharlamov A, Jones SC, Kim DK (2002) Suramin reduces infarct volume in a model of focal brain ischemia in rats. Exp Brain Res 147:353–359

    PubMed  CAS  Google Scholar 

  337. Krügel U, Kittner H, Franke H, Illes P (2001) Accelerated functional recovery after neuronal injury by P2 receptor blockade. Eur J Pharmacol 420:R3–R4

    PubMed  Google Scholar 

  338. Weissman TA, Riquelme PA, Ivic L, Flint AC, Kriegstein AR (2004) Calcium waves propagate through radial glial cells and modulate proliferation in the developing neocortex. Neuron 43:647–661

    PubMed  CAS  Google Scholar 

  339. Kunapuli SP, Dorsam RT, Kim S, Quinton TM (2003) Platelet purinergic receptors. Curr Opin Pharmacol 3:175–180

    PubMed  CAS  Google Scholar 

  340. Dorsam RT, Kunapuli SP (2004) Central role of the P2Y12 receptor in platelet activation. J Clin Invest 113:340–345

    PubMed  CAS  Google Scholar 

  341. Fam SR, Paquet M, Castleberry AM, Oller H, Lee CJ, Traynelis SF, Smith Y, Yun CC, Hall RA (2005) P2Y1 receptor signaling is controlled by interaction with the PDZ scaffold NHERF-2. Proc Natl Acad Sci USA 102:8042–8047

    PubMed  CAS  Google Scholar 

  342. Chattaraj SC (2001) Cangrelor AstraZeneca. Curr Opin Investig Drugs 2:250–255

    PubMed  CAS  Google Scholar 

  343. Burnstock G (2002) Potential therapeutic targets in the rapidly expanding field of purinergic signalling. Clin Med 2:45–53

    PubMed  CAS  Google Scholar 

  344. Mamedova L, Capra V, Accomazzo MR, Gao ZG, Ferrario S, Fumagalli M, Abbracchio MP, Rovati GE, Jacobson KA (2005) CysLT1 leukotriene receptor antagonists inhibit the effects of nucleotides acting at P2Y receptors. Biochem Pharmacol 71:115–125

    PubMed  CAS  Google Scholar 

  345. Ballerini P, Di Iorio P, Ciccarelli R, Caciagli F, Poli A, Beraudi A, Buccella S, D’Alimonte I, D’Auro M, Nargi E, Patricelli P, Visini D, Traversa U (2005) P2Y1 and cysteinyl leukotriene receptors mediate purine and cysteinyl leukotriene co-release in primary cultures of rat microglia. Int J Immunopathol Pharmacol 18:255–268

    PubMed  CAS  Google Scholar 

  346. Kennedy C, Assis TS, Currie AJ, Rowan EG (2003) Crossing the pain barrier: P2 receptors as targets for novel analgesics. J Physiol 553:683–694

    PubMed  CAS  Google Scholar 

  347. Günther A, Manaenko A, Franke H, Wagner A, Schneider D, Berrouschot J, Reinhardt R (2004) Hyperbaric and normobaric reoxygenation of hypoxic rat brain slices-impact on purine nucleotides and cell viability. Neurochem Int 45:1125–1132

    PubMed  Google Scholar 

  348. Jarvis MF, Burgard EC, McGaraughty S, Honore P, Lynch K, Brennan TJ, Subieta A, Van Biesen T, Cartmell J, Bianchi B, Niforatos W, Kage K, Yu H, Mikusa J, Wismer CT, Zhu CZ, Chu K, Lee CH, Stewart AO, Polakowski J, Cox BF, Kowaluk E, Williams M, Sullivan J, Faltynek C (2002) A-317491, a novel potent and selective non-nucleotide antagonist of P2X3 and P2X2/3 receptors, reduces chronic inflammatory and neuropathic pain in the rat. Proc Natl Acad Sci USA 99:17179–17184

    PubMed  CAS  Google Scholar 

  349. Lämmer A, Günther A, Beck A, Krügel U, Kittner H, Schneider D, Illes P, Franke H (2006) Neuroprotective effects of the P2 receptor antagonist PPADS on focal cerebral ischemia induced injury in rats. Eur J Neurosci (in press)

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Authors and Affiliations

  1. Rudolf-Boehm Institute of Pharmacology and Toxicology, University of Leipzig, Härtelstrasse 16-18, 04107, Leipzig, Germany

    Heike Franke, Ute Krügel & Peter Illes

  2. Interdisciplinary Center for Clinical Research, Medical Faculty, University of Leipzig, Leipzig, Germany

    Peter Illes

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  1. Heike Franke
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  2. Ute Krügel
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  3. Peter Illes
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Correspondence to Heike Franke.

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Franke, H., Krügel, U. & Illes, P. P2 receptors and neuronal injury. Pflugers Arch - Eur J Physiol 452, 622–644 (2006). https://doi.org/10.1007/s00424-006-0071-8

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  • DOI: https://doi.org/10.1007/s00424-006-0071-8

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