Purinergic Signalling

, Volume 5, Issue 2, pp 223–232 | Cite as

Physiological and pathological functions of P2X7 receptor in the spinal cord

Original Article


ATP-mediated signaling has widespread actions in the nervous system from neurotransmission to regulation of proliferation. In addition, ATP is released during injury and associated to immune and inflammatory responses. Still, the potential of therapeutic intervention of purinergic signaling during pathological states is only now beginning to be explored because of the large number of purinergic receptors subtypes involved, the complex and often overlapping pharmacology and because ATP has effects on every major cell type present in the CNS. In this review, we will focus on a subclass of purinergic-ligand-gated ion channels, the P2X7 receptor, its pattern of expression and its function in the spinal cord where it is abundantly expressed. We will discuss the mechanisms for P2X7R actions and the potential that manipulating the P2X7R signaling pathway may have for therapeutic intervention in pathological events, specifically in the spinal cord.


ATP Purinergic signaling P2X receptors Neuronal injury P2X7 antagonists 



This work was supported by NINDS NS38073, NS39559, and NS050315; The Adelson Program in Neural Repair and Regeneration, The New York State Spinal Cord Research Board, and the Robert Packard Center for ALS Research.


  1. 1.
    Burnstock G (2006) Purinergic signaling. Br J Pharmacol 147:S172–S181PubMedGoogle Scholar
  2. 2.
    Inoue K Koizumi S, Tsuda M (2007) The role of nucleotides in the neuron-glia communication responsible for the brain functions. J Neurochem 102:1447–1458Google Scholar
  3. 3.
    Burnstock G (2007) Physiology and pathophysiology of purinergic neurotransmission. Physiol Rev 87:659–797PubMedGoogle Scholar
  4. 4.
    Kennedy C, Saville VL, Burnstock G (1986) The contributions of noradrenaline and ATP to the responses of the rabbit central ear artery to sympathetic nerve stimulation depend on the parameters of stimulation. Eur J Pharmacol 122:21–300Google Scholar
  5. 5.
    Jo YH, Schlichter R (1999) Synaptic corelease of ATP and GABA in cultured spinal neurons. Nat Neurosci 2:241–245PubMedGoogle Scholar
  6. 6.
    Guthrie PB, Knappenberg J, Segal M, Bennett MV, Charles AC, Kater SB (1999) ATP from astrocytes mediates glial calcium waves. J Neurosci 19:520–528PubMedGoogle Scholar
  7. 7.
    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 99:9840–9845PubMedGoogle Scholar
  8. 8.
    Zhang J, Wang H, Ye C, Ge W, Chen Y, Jiang ZL, Wu CP, Poo MM, Duan S (2003) ATP released by astrocytes mediates glutamatergic activity-dependent heterosynaptic suppression. Neuron 40:971–982PubMedGoogle Scholar
  9. 9.
    Pascual O, Casper KB, Kubera C, Zhang J, Revilla-Sanchez R, Sul JY, Takano H, Moss SJ, McCarthy K, Haydon PG (2005) Astrocytic purinergic signaling coordinates synaptic networks. Science 310:113–116PubMedGoogle Scholar
  10. 10.
    Wang X, Lou N, Xu Q, Tian GF, Peng WG, Han X, Kang J, Takano T, Nedergaard M (2006) Astrocytic Ca2+ signaling evoked by sensory stimulation in vivo. Nat Neurosci 9:816–823PubMedGoogle Scholar
  11. 11.
    Agresti C, Meomartini ME, Amadio S, Ambrosini E, Serafini B, Franchini L, Volonté C, Aloisi F, Visentin S (2005) Metabotropic P2 receptor activation regulates oligodendrocyte progenitor migration and development. Glia 50:132–144PubMedGoogle Scholar
  12. 12.
    Franke H, Iles P (2006) Involvement of P2 receptors in the growth and survival of neurons in the CNS. Pharmacol Ther 109:297–324PubMedGoogle Scholar
  13. 13.
    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. Nature Neurosci 8:752–758PubMedGoogle Scholar
  14. 14.
    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 10:821–827PubMedGoogle Scholar
  15. 15.
    North A (2002) Molecular physiology of P2X receptors. Physiol Rev 82:1013–1067PubMedGoogle Scholar
  16. 16.
    Cockcroft S, Gomperts BD (1979) ATP induces nucleotide permeability in rat mast cells. Nature 279:541–542PubMedGoogle Scholar
  17. 17.
    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 272:735–738PubMedGoogle Scholar
  18. 18.
    Le Feuvre R, Brough D, Rothwell N (2002) Extracellular ATP and P2X7 receptors in neurodegeneration. Eur J Pharmacol 447:261–269PubMedGoogle Scholar
  19. 19.
    Khakh BS, North A (2006) P2X receptors as cell-surface ATP sensors in health and disease. Nature 442:527–532PubMedGoogle Scholar
  20. 20.
    Sanz JM, DiVirgilio F (2000) Kinetics and mechanism of ATP-dependent IL-1β release from microglia cells. J Immunol 164:4893–4898PubMedGoogle Scholar
  21. 21.
    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 23:1320–1328PubMedGoogle Scholar
  22. 22.
    León D, Hervás C, Miras-Portugal MT (2006) P2Y1 and P2X7 receptors induce calcium/calmodulin-dependent protein kinase II phosphorylation in cerebellar granule neurons. Eur J Neurosci 23:2999–3013PubMedGoogle Scholar
  23. 23.
    Donnelly-Roberts DL, Namovic M, Faltynek CR, Jarvis MF (2004) Mitogen-activated protein kinase and caspase signaling pathways are required for P2X7 receptor (P2X7R)-induced pore formation in human THP-1 cells. J Pharmacol Exp Ther 308:1053–1061PubMedGoogle Scholar
  24. 24.
    Faria RX, DeFarias FP, Alves LA (2005) Are second messengers crucial for opening the pore associated with P2X7 receptor? Am J Physiol Cell Physiol 288:C260–C271PubMedGoogle Scholar
  25. 25.
    Jiang LH, Rassendren F, Mackenzie A, Zhang YH, Surprenant A, North RA (2005) N-methyl-d-glucamine and propidium dyes utilize different permeation pathways at rat P2X7 receptors. Am J Physiol Cell Physiol 289:1295–1302Google Scholar
  26. 26.
    Donnelly-Roberts DL, Jarvis MF (2007) Discovery of P2X7 receptor-selective antagonists offers new insights into P2X7 receptor function and indicates a role in chronic pain states. Brit J Pharmacol 151:571–579Google Scholar
  27. 27.
    Hervé JC, Phelan P, Bruzzone R, White TW (2005) Connexins, innexins and pannexins: bridging the communication gap. Biochim Biophys Acta 1719:3–5PubMedGoogle Scholar
  28. 28.
    Pelegrin P, Surprenant A (2006) Pannexin-1 mediates large pore formation and interleukin-1β release by the ATP-gated P2x7 receptor. EMBO J 25:5071–5082PubMedGoogle Scholar
  29. 29.
    Pelegrin P, Surprenant A (2007) Pannexin-1 couples to maitotoxin and nigericin-induced interleukin-1β release through a dye uptake-independent pathway. J Biol Chem 4:2386–2394Google Scholar
  30. 30.
    Sperlách B, Vizi ES, Wirkner K, Illes P (2006) P2X7 receptors in the nervous system. Prog Neurobiol 78:327–346Google Scholar
  31. 31.
    Illes P, Ribeiro JA (2004) Molecular physiology of P2 receptors in the central nervous system. Eur J Pharmacol 483:5–17PubMedGoogle Scholar
  32. 32.
    Collo G, Neidhart S, Kawashima E, Kosco-Vilbois M, North RA, Buell G (1997) Tissue distribution of the P2X7 receptor. Neuropharmacol 36:1277–1283Google Scholar
  33. 33.
    Deuchars SA, Atkinson L, Booke 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 system. J Neurosci 21:7143–7152PubMedGoogle Scholar
  34. 34.
    Sperlágh B, Köfalvi 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 81:1196–211PubMedGoogle Scholar
  35. 35.
    Armstrong JN, Brust TB, Lewis RG, MacVivar BA (2002) Activation of presynaptic P2X7-like receptors depresses mossy fiber-CA3 synaptic transmission through p38 mitogen-activated protein kinase. J Neurosci 22:5938–5945PubMedGoogle Scholar
  36. 36.
    Deng Z, Fyffe RE (2004) Expression of P2X7 receptor immunoreactivity in distinct subsets of synaptic terminals in the ventral horn of rat lumbar spinal cord. Brain Res 1020:53–61PubMedGoogle Scholar
  37. 37.
    Atkinson L, Battern TF, Moores TS, Varoqui H, Erickson JD, Deuchars J (2004) Differential co-localization of the P2X7 receptor subunit with vesicular glutamate transporters VGLUT1 and VGLUT2 in rat CNS. Neurosci 123:761–768Google Scholar
  38. 38.
    Sim JA, Young MT, Sung HY, North A, Surprenant A (2004) Reanalysis of P2X7 receptor expression in rodent brain. J Neurosci 24:6307–6314PubMedGoogle Scholar
  39. 39.
    Anderson CM, Nedergaard M (2006) Emerging challenges of assigning P2X7 receptor function and immunoreactivity in neurons. TINS 29:258–262Google Scholar
  40. 40.
    Yu Y, Ugawa S, Ueda T, Ishida Y, Inoue K, Nyunt AK, Umemura A, Mase K, Yamada K, Shimada S (2008) Cellular localization of P2X7 receptor mRNA in the rat brain. Brain Res 1194:45–55PubMedGoogle Scholar
  41. 41.
    Rhee JS, Wang ZM, Nabekura J, Inoue K, Akaike N (2000) ATP facilitates spontaneous glycinergic IPSC frequency at dissociated rat dorsal horn interneuron synapses. J Physiol 524:471–483PubMedGoogle Scholar
  42. 42.
    Hugel S, Schlichter R (2000) Presynaptic P2X receptors facilitate inhibitory GABAergic transmission between cultured rat spinal cord dorsal horn neurons. J Neurosci 20:2121–2130PubMedGoogle Scholar
  43. 43.
    Nakatsuka T, Tsuzuki K, Ling JX, Sonobe H, Gu JG (2003) Distinct roles of P2X receptors in modulating glutamate release at different primary sensory synapses in rat spinal cord. J Neurophysiol 89:3243–3252PubMedGoogle Scholar
  44. 44.
    Bardoni R, Goldstein PA, Lee CJ, Gu JG, MacDermott AB (1997) ATP P2X receptors mediate fast synaptic transmission in the dorsal horn of the rat spinal cord. J Neurosci 17:5297–5304PubMedGoogle Scholar
  45. 45.
    Gu JG, MacDermott AB (1997) Activation of ATP P2X receptors elicits glutamate release from sensory neuron synapses. Nature 389:749–753PubMedGoogle Scholar
  46. 46.
    Shiokawa H, Nakatsuka T, Furue H, Tsuda M, Katafuchi T, Inoue K, Yoshimura M (2006) Direct excitation of deep dorsal horn neurons in the rat spinal cord by the activation of postsynaptic P2X receptors. J Physiol 573:753–763PubMedGoogle Scholar
  47. 47.
    Nakatsuka T, Gu JG (2006) P2X purinoceptors and sensory transmission. Pflugers Arch 452:598–607PubMedGoogle Scholar
  48. 48.
    Panenka W, Jijon H, Herx LM, Armstrong JN, Feighan D, Wei T, Yong VW, Ransohoff RM, MacVivar BA (2001) P2X7-like receptor activation in astrocytes increases chemokine monocyte chemoattractant protein-1 expression via mitogen-activated protein kinase. J Neurosci 21:7135–7142PubMedGoogle Scholar
  49. 49.
    Kukley M, Barden JA, Steinhauser C, Jabs R (2001) Distribution of P2X receptors on astrocytes in juvenile rat hippocampus. Glia 36:11–21PubMedGoogle Scholar
  50. 50.
    Fumagalli M, Brambilla R, D’Ambrosi N, Volonté C, Matteoli M, Verderio C, Abbracchio MP (2003) Nucleotide-mediated calcium signaling in rat cortical astrocytes. Role of P2X and P2Y receptors. Glia 43:218–230PubMedGoogle Scholar
  51. 51.
    Hung AC, Chu Y-J, Lin Y-H, Weng J-Y, Chen HB, Au Y-C, Sun SH (2005) Roles of protein kinase C in regulation of P2X7 receptor-mediated calcium signaling of cultured type-2 astrocyte cell line, RBA-2. Cell Signal 17:1384–1396PubMedGoogle Scholar
  52. 52.
    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-benzoylbenzoyl)-ATP. J Neurosci 24:7128–7139PubMedGoogle Scholar
  53. 53.
    Jabs R, Grote A, Grauer M, Seifert G, Steinhauser C (2007) Lack of P2X Receptor mediated currents in astrocytes and GluR type glial cells of the hippocampal CA1 region. Glia 55:1648–1655PubMedGoogle Scholar
  54. 54.
    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 49:245–258PubMedGoogle Scholar
  55. 55.
    Haydon PG, Carmignoto G (2006) Astrocyte control of synaptic transmission and neurovascular coupling. Physiol Rev 86:1009–1031PubMedGoogle Scholar
  56. 56.
    Zhang X, Chen Y, Wang C, Huang LYM (2007) Neuronal somatic ATP release triggers neuron-satellite glial cell communication in dorsal root ganglia. PNAS 104:9864–9869PubMedGoogle Scholar
  57. 57.
    Suadicani SO, Brosnan CF, Scemes E (2006) P2X7 receptors mediate ATP release and amplification of astrocytic intercellular Ca2+ signaling. J Neurosci 26:1378–1385PubMedGoogle Scholar
  58. 58.
    James G, Butt AM (2002) P2Y and P2X purinoceptor mediated Ca2+ signaling in glial cell pathology in the central nervous system. Eur J Pharmacol 447:247–260PubMedGoogle Scholar
  59. 59.
    Jorgensen NR, Henriksen Z, Sorensen OH, Eriksen EF, Civitelli R, Steinberg TH (2002) Intercellular calcium signaling occurs between human osteoblasts and osteoclasts and requires activation of osteoclast P2X7 receptors. J Biol Chem 277:7574–7580PubMedGoogle Scholar
  60. 60.
    Verderio C, Matteoli M (2001) ATP mediates calcium signaling between astrocytes and microglial cells: modulation by IFN-γ. J Immunol 166:6383–6391PubMedGoogle Scholar
  61. 61.
    Xiang Z, Burnstock G (2005) Expression of P2X receptors on rat microglial cells during early development. Glia 52:119–126PubMedGoogle Scholar
  62. 62.
    Rappold PM, Lynd-Balta E, Joseph SA (2006) P2X7 receptor immunoreactive profile confined to resting and activated microglia in the epileptic brain. Brain Res 1089:171–178PubMedGoogle Scholar
  63. 63.
    Casanovas A, Hernández S, Tarabal O, Rosselló J, Esquerda JE (2008) Strong P2X4 purinergic receptor-like immunoreactivity is selectively associated with degenerating neurons in transgenic rodent models of amyotrophic lateral sclerosis. J Comp Neurol 506:75–92PubMedGoogle Scholar
  64. 64.
    Colomar A, Amédée T (2001) ATP stimulation of P2X7 receptor activates three different ionic conductances in cultured mouse Schwann cells. Eur J Neurosci 14:927–936PubMedGoogle Scholar
  65. 65.
    Chessell IP, Hatcher J, Bountra C, Michel AD, Hughes JP, Green P, Egerton J, Murfin M, Richardson J, Peck WL et al (2005) Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain. Pain 114:386–396PubMedGoogle Scholar
  66. 66.
    Inoue K (2006) ATP receptors of microglia involved in pain. Novartis Found Symp 276:263–272PubMedGoogle Scholar
  67. 67.
    Solle M, Labasi J, Perregaux DG, Stam E, Petrushova N, Koller BH, Griffiths RJ, Gabel CA (2001) Altered cytokine production in mice lacking P2X7 receptors. J Biol Chem 276:125–132PubMedGoogle Scholar
  68. 68.
    Honore P, Donnelly-Roberts D, Namovic MT, Hsieh G, Zhu CZ, Mikusa JP, Hernandez G, Zhong C, Gauvin DM, Chandran P, Harris R, Medrano AP, Carroll W, Marsh K, Sullivan JP, Faltynek CR, Jarvis MF (2006) A-740003 [N-(1-{[(cyanoimino)(5-quinolinylamino) methyl] amino}-2,2-dimethylpropyl)-2-(3,4-dimethoxyphenyl) acetamide], a novel and selective P2X7 receptor antagonist, dose-dependently reduces neuropathic pain in the rat. J Pharmacol Exp Ther 319:1376–1385PubMedGoogle Scholar
  69. 69.
    Nelson DW, Gregg RJ, Kort ME, Perez-Medrano A, Voight EA, Wang Y, Grayson G, Namovic MT, Donnelly-Roberts DL, Niforatos W, Honore P, Jarvis MF, Faltynek CR, Carroll WA (2006) Structure-activity relationship studies on a series of novel, substituted 1-benzyl-5-phenyltetrazole P2X7 antagonists. J Med Chem 49:3659–3666PubMedGoogle Scholar
  70. 70.
    Suzuki T, Hide I, Katsutoshi I, Kohsaka S, Inoue K, Nakata Y (2004) Production and release of neuroprotective tumor necrosis factor by P2X7 receptor-activated microglia. J Neurosci 24:1–7PubMedGoogle Scholar
  71. 71.
    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 278:12309–12317Google Scholar
  72. 72.
    McLarson JG, Ryuy JK, Walker DG, Choi HB (2006) Upregulated expression of purinergic p2x7 receptor in Alzheimer disease and amyloid-beta peptide-treated microglia and in peptide-injected rat hippocampus. Neuropathol Exp Neurol 65:1090–1097Google Scholar
  73. 73.
    Yiangou Y, Facer P, Durrenberger P, Chessell IP, Naylor A, Bountra C, Banati RR, Anand P (2006) COX-2, CB2 and P2X7-immunoreactivities are increased in activated microglial cells/macrophages of multiple sclerosis and amyotrophic lateral sclerosis spinal cord. BMC Neurol 6:12PubMedGoogle Scholar
  74. 74.
    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 63:686–699PubMedGoogle Scholar
  75. 75.
    Morioka N, Abdin MJ, Kitayama T, Morita K, Nakata Y, Dohi T (2008) P2X7 receptor stimulation in primary cultures of rat spinal microglia induces downregulating of the activity for glutamate transport. Glia 56:528–538PubMedGoogle Scholar
  76. 76.
    Bianco F, Ceruti S, Colombo A, Fumagalli M, Ferrari D, Pizzirani C, Matteoli M, Di Virgilio F, Abbracchio MP, Verderio C (2006) A role for P2X7 in microglial proliferation. J Neurochem 99:745–758PubMedGoogle Scholar
  77. 77.
    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 26:974–982PubMedGoogle Scholar
  78. 78.
    Beigi RD, Kertesy SB, Aquilina G, Dubyak GR (2003) Oxidized ATP (oATP) attenuates proinflammatory signaling via P2 receptor-independent mechanisms. Br J Pharmacol 140:507–519PubMedGoogle Scholar
  79. 79.
    Chen L, Brosnan CF (2006) Exacerbation of experimental encephalomyelitis in P2X7R−/− mice: evidence for loss of apopototic activity in lympocytes. J Immunol 176:3115–3126PubMedGoogle Scholar
  80. 80.
    Lalancette-Hébert M, Gowing G, Simard A, Weng YC, Kriz J (2007) Selective ablation of proliferating microglial cells exacerbates ischemic injury in the brain. J Neurosci 27:2596–2605PubMedGoogle Scholar
  81. 81.
    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 23:381–384PubMedGoogle Scholar
  82. 82.
    Imai F, Suzuki H, Oda J, Ninomiya T, Ono K, Sano H, Sawada M (2007) Neuroprotective effect of exogenous microglia in global brain ischemia. J Cereb Blood Flow Metab 27:488–500PubMedGoogle Scholar
  83. 83.
    Koizumi S, Shigemoto-Mogami Y, Nasu-Tada K, Shinozaki Y, Ohsawa K, Tsuda M, Joshi BV, Jacobson KA, Kohsaka S, Inoue K (2007) UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 446:1091–1095PubMedGoogle Scholar
  84. 84.
    Andries M, Damme PV, Robberecht W, Van Den Bosch L (2007) Ivermectin inhibits AMPA receptor-mediated excitotoxicity in cultured motor neurons and extends the life span of a transgenic mouse model of amyotrophic lateral sclerosis. Neurobiol Dis 25:8–16PubMedGoogle Scholar
  85. 85.
    Jacobson KA, Jarvis MF, Williams M (2002) Purine and pyrimidine (P2) receptors as drug targets. J Med Chem 45:4057–4093PubMedGoogle Scholar
  86. 86.
    Freissmuth M, Boehm S, Beindl W, Nickel P, Ijzerman AP, Hohenegger M, Nanoff C (1996) Suramin analogues as subtype-selective G protein inhibitors. Mol Pharmacol 49:602–611PubMedGoogle Scholar
  87. 87.
    North RA, Surprenant A (2000) Pharmacology of cloned P2X receptors. Annu Rev Pharmacol Toxicol 40:563–580PubMedGoogle Scholar
  88. 88.
    Ciccarelli R, Ballerini P, Sabatino G, Rathbone MP, D’Onofrio M, Caciagli F, Iorio P (2001) Involvement of astrocytes in purine-mediated reparative processes in the brain. Int J Devl Neurosci 19:395–414Google Scholar
  89. 89.
    Zimmermann H (2006) Ectonucleotidases in the nervous system. Novartis Found Symp 276:113–128PubMedGoogle Scholar
  90. 90.
    Sperlágh B, Szabó G, Erdélyi F, Baranyi M, Vizi ES (2003) Homo- and heteroexchange of adenine nucleotides and nucleosides in rat hippocampal slices by the nucleoside transport system. Br J Pharmacol 139:623–633PubMedGoogle Scholar
  91. 91.
    Sánchez-Nogueiro J, Marín-García P, Miras-Portugal MT (2005) Characterization of a functional P2X7-like receptor in cerebellar granule neurons from P2X7 knockout mice. FEBS Lett 579:3783–3788PubMedGoogle Scholar
  92. 92.
    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 135:1616–1626PubMedGoogle Scholar
  93. 93.
    Hervás C, Pérez-Sen R, Miras-Portugal MT (2005) Presence of diverse functional P2X receptors in rat cerebellar synaptic terminals. Bioch Pharmacol 70:770–785Google Scholar
  94. 94.
    Miras-Portugal MT, Díaz-Hernández M, Giráldez L, Hervás C, Gómez-Villafuertes R, Sen RP, Gualix J, Pintor J (2003) P2X7 receptors in rat brain: presence in synaptic terminals and granule cells. Neurochem Res 28:1597–1605PubMedGoogle Scholar
  95. 95.
    Kobayashi K, Fukuoka T, Yamanaka H, Dai Y, Obata K, Tokunaga A, Noguchi K (2005) Differential expression patterns of mRNAs for P2X receptor subunits in neurochemically characterized dorsal root ganglion neurons in the rat. J Comp Neurol 481:377–390PubMedGoogle Scholar
  96. 96.
    Brändle U, Kohler K, Wheeler-Schilling TH (1998) Expression of the P2X7-receptor subunit in neurons of the rat retina. Mol Brain Res 62:106–109PubMedGoogle Scholar
  97. 97.
    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 459:267–277PubMedGoogle Scholar
  98. 98.
    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 18:417–430PubMedGoogle Scholar
  99. 99.
    D'Alimonte I, Ciccarelli R, Di Iorio P, Nargi E, Buccella S, Giuliani P, Rathbone MP, Jiang S, Caciagli F, Ballerini P (2007) Activation of P2X(7) receptors stimulates the expression of P2Y(2) receptor mRNA in astrocytes cultured from rat brain. Int J Immunopathol Pharmacol 20:301–316PubMedGoogle Scholar
  100. 100.
    Lee M, Lee SJ, Choi HJ, Jung YW, Frøkiæ J, Nielsen S, Kwon TH (2008) Regulation of AQP4 protein expression in rat brain astrocytes: role of P2X7 receptor activation. Brain Res 1195:1–11PubMedGoogle Scholar
  101. 101.
    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 141:1106–1117PubMedGoogle Scholar
  102. 102.
    Hide I, Tanaka M, Inoue A, Nakajima K, Kohsaka S, Inoue K, Nakata Y (2000) Extracellular ATP triggers tumor necrosis factor-α release from rat microglia. J Neurochem 75:965–972PubMedGoogle Scholar
  103. 103.
    Chafke Y, Seguin R, Antel JP, Morissette C, Malo D, Henderson D, Séguéla P (2002) ADP and AMP induce Interleukin-1b release from microglial cells through activation of ATP-primed P2X7 receptor channels. J Neurosci 22:3061–3069Google Scholar
  104. 104.
    Mingam R, De Smedt V, Amédée T, Bluthé RM, Kelley KW, Dantzer R, Layé S (2008) In vitro and in vivo evidence for a role of the P2X7 receptor in the release of IL-1 beta in the murine brain. Brain Behav Immun 22:234–44PubMedGoogle Scholar
  105. 105.
    Skaper SD, Facci L, Culbert AA, Evans NA, Chessell I, Davis JB, Richardson JC (2006) P2X7 receptors on microglial cells mediate injury to cortical neurons in vitro. Glia 54:234–242PubMedGoogle Scholar
  106. 106.
    Pannicke T, Fischer W, Biedermann B, Schädlich H, Grosche J, Faude F, Wiedemann P, Allgaier C, Illes P, Burnstock G, Reichenbach A (2000) P2X7 receptors in Müller glial cells from the human retina. J Neurosci 20:5965–5972PubMedGoogle Scholar
  107. 107.
    Bianchi BR, Lynch KJ, Touma E, Niforatos W, Burgard EC, Alexander KM, Park HS, Yu H, Metzger R, Kowaluk E, Jarvis MF, van Biesen T (1999) Pharmacological characterization of recombinant human and rat P2X receptor subtypes. Eur J Pharmacol 376:127–138PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  1. 1.Division of Glial Disease and Therapeutics, Center for Translational NeuromedicineUniversity of Rochester Medical CenterRochesterUSA

Personalised recommendations