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Cellular and Molecular Biology Letters

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Volume 20, Issue 5


Purinergic signaling and the functioning of the nervous system cells

Kamila Puchałowicz
  • Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 72 Powstańców Wlkp. St., 70-111 Szczecin, Poland
  • Other articles by this author:
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/ Irena Baranowska-Bosiacka
  • Corresponding author
  • Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 72 Powstańców Wlkp. St., 70-111 Szczecin, Poland
  • Email
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Violetta Dziedziejko
  • Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 72 Powstańców Wlkp. St., 70-111 Szczecin, Poland
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
/ Dariusz Chlubek
  • Department of Biochemistry and Medical Chemistry, Pomeranian Medical University, 72 Powstańców Wlkp. St., 70-111 Szczecin, Poland
  • Other articles by this author:
  • De Gruyter OnlineGoogle Scholar
Published Online: 2016-03-05 | DOI: https://doi.org/10.1515/cmble-2015-0050


Purinergic signaling in the nervous system has been the focus of a considerable number of studies since the 1970s. The P2X and P2Y receptors are involved in the initiation of purinergic signaling. They are very abundant in the central and peripheral nervous systems, where they are expressed on the surface of neurons and glial cells - microglia, astrocytes, oligodendrocytes and Schwann cells and the precursors of the latter two. Their ligands - extracellular nucleotides - are released in the physiological state by astrocytes and neurons forming synaptic connections, and are essential for the proper functioning of nervous system cells. Purinergic signaling plays a crucial role in neuromodulation, neurotransmission, myelination in the CNS and PNS, intercellular communication, the regulation of ramified microglia activity, the induction of the response to damaging agents, the modulation of synaptic activity and other glial cells by astrocytes, and the induction of astrogliosis. Understanding these mechanisms and the fact that P2 receptors and their ligands are involved in the pathogenesis of diseases of the nervous system may help in the design of drugs with different and more effective mechanisms of action.

Keywords: Astrocytes; ATP; Calcium waves; Extracellular nucleotides; Microglia; Myelination; Neurons; Neurotransmission; P2X receptors; P2Y receptors


  • 1. Abbracchio, M.P., Burnstock, G., Verkhratsky, A. and Zimmermann, H. Purinergic signaling in the nervous system: an overview. Trends Neurosci. 32 (2009) 19-29.CrossrefGoogle Scholar

  • 2. Helenius, M., Jalkanen, S. and Yegutkin, G. Enzyme-coupled assays for simultaneous detection of nanomolar ATP, ADP, AMP, adenosine, inosine and pyrophosphate concentrations in extracellular fluids. Biochim. Biophys. Acta 1823 (2012) 1967-1975.Google Scholar

  • 3. Bianchi, M.E. DAMPs, PAMPs and alarmins: all we need to know about danger. J. Leukoc. Biol. 81 (2007) 1-5.Google Scholar

  • 4. Rodrigues, R.J., Tomé, A.R. and Cunha, R.A. ATP as a multi-target danger signal in the brain. Front. Neurosci. 9 (2015) 148. DOI: 10.3389/fnins.2015.00148.CrossrefGoogle Scholar

  • 5. Burnstock, G. and Kennedy, C. Is there a basis for distinguishing two types of P2-purinoceptor? Gen. Pharmacol. 6 (1985) 433-440.CrossrefGoogle Scholar

  • 6. Khakh, B.S. and North, R.A. Neuromodulation by extracellular ATP and P2X receptors in the CNS. Neuron 76 (2012) 51-69.CrossrefGoogle Scholar

  • 7. Jacobson, K.A., Jayasekara, M.P. and Costanzi, S. Molecular structure of P2Y receptors: mutagenesis, modeling and chemical probes. Wiley Interdiscip. Rev. Membr. Transp. Signal. 1 (2012) WMTS68. DOI: 10.1002/wmts.68.CrossrefGoogle Scholar

  • 8. Burnstock, G. Purinergic signaling: past, present and future. Braz. J. Med. Biol. Res. 42 (2009) 3-8.Google Scholar

  • 9. Burnstock, G., Campbell, G., Satchell, D. and Smythe, A. Evidence that adenosine triphosphate or a related nucleotide is the transmitter substance released by non-adrenergic inhibitory nerves in the gut. Br. J. Pharmacol. 40 (1970) 668-688.Google Scholar

  • 10. Burnstock, G. Neural nomenclature. Nature 229 (1971) 282-283.Google Scholar

  • 11. Burnstock, G. Purinergic nerves. Pharmacol. Rev. 24 (1972) 509-581.Google Scholar

  • 12. Evans, R.J., Derkach, V. and Surprenant, A. ATP mediates fast synaptic transmission in mammalian neurons. Nature 357 (1992) 503-505.Google Scholar

  • 13. Edwards, F.A., Gibb, A.J. and Colquhoun, D. ATP receptor-mediated synaptic currents in the central nervous system. Nature 359 (1992) 144-147.Google Scholar

  • 14. Burnstock, G. A basis for distinguishing two types of purinergic receptor. In: Cell Membrane Receptors for Drugs and Hormones: A Multidisciplinary Approach. (Straub, R.W. and Bolis, L., Eds.), Raven Press, New York, 1978, 107-118.Google Scholar

  • 15. Purinergic signaling and the nervous system (Burnstock, G. and Verkhratsky, A., Ed.), Springer, Berlin/Heidelberg, 2012, 1-715.Google Scholar

  • 16. Abbracchio, M.P., Burnstock, G., Boeynaems, J.-M., Barnard, E.A., Boyer, J.L., Kennedy, C., Knight, G.E., Fumagalli, M., Gachet, C., Jacobson, K.A. and Weisman, G.A. International Union of Pharmacology. Update and subclassification of the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol. Rev. 58 (2006) 281-341.CrossrefGoogle Scholar

  • 17. Kettenmann, H., Hanisch, U.K., Noda, M. and Verkhratsky, A. Physiology of microglia. Physiol. Rev. 91 (2011) 461-553.CrossrefGoogle Scholar

  • 18. Zimmermann, H. Ectonucleotidases in the nervous system. Novartis Found. Symp. 276 (2006) 113-128.Google Scholar

  • 19. Burnstock, G. Purinergic receptors and pain. Curr. Pharm. Des. 15 (2009) 1717-1735.CrossrefGoogle Scholar

  • 20. Pankratov, Y., Lalo, U., Verkhratsky, A. and North, R.A. Vesicular release of ATP at central synapses. Pflugers Arch. 452 (2006) 589-597.Google Scholar

  • 21. Hiasa, M., Togawa, N. and Moriyama, Y. Vesicular nucleotide transport: a brief history and the vesicular nucleotide transporter as a target for drug development. Curr. Pharm. Des. 20 (2014) 2745-2749.CrossrefGoogle Scholar

  • 22. Sawada, K., Echigo, N., Juge, N., Miyaji, T., Otsuka, M., Omote, H., Yamamoto, A. and Moriyama, Y. Identification of a vesicular nucleotide transporter. Proc. Natl. Acad. Sci. U.S.A. 105 (2008) 5683-5686.CrossrefGoogle Scholar

  • 23. Oya, M., Kitaguchi, T., Yanagihara, Y., Numano, R., Kakeyama, M., Ikematsu, K. and Tsuboi, T. Vesicular nucleotide transporter is involved in ATP storage of secretory lysosomes in astrocytes. Biochem. Biophys. Res. Commun. 438 (2013) 145-151.Google Scholar

  • 24. Imura, Y., Morizawa, Y., Komatsu, R., Shibata, K., Shinozaki, Y., Kasai, H., Moriishi, K., Moriyama, Y. and Koizumi, S. Microglia release ATP by exocytosis. Glia 61 (2013) 1320-1330.CrossrefGoogle Scholar

  • 25. Fitz, J.G. Regulation of cellular ATP release. Trans. Am. Clin. Climatol. Assoc. 118 (2007) 199-208.Google Scholar

  • 26. Thyssen, A., Hirnet, D., Wolburg, H., Schmalzing, G., Deitmer, J.W. and Lohr, C. Ectopic vesicular neurotransmitter release along sensory axons mediates neurovascular coupling via glial calcium signaling. Proc. Natl. Acad. Sci. U.S.A. 107 (2010) 15258-15263.CrossrefGoogle Scholar

  • 27. Zhang, X., Chen, Y., Wang, C. and Huang, L.Y. Neuronal somatic ATP release triggers neuron-satellite glial cell communication in dorsal root ganglia. Proc. Natl. Acad. Sci. U.S.A. 104 (2007) 9864-9869.CrossrefGoogle Scholar

  • 28. Burnstock, G. Unresolved issues and controversies in purinergic signaling. J. Physiol. 586 (2008) 3307-3312.Google Scholar

  • 29. Scemes, E., Suadicani, S.O., Dahl, G. and Spray, D.C. Connexin and pannexin mediated cell-cell communication. Neuron Glia Biol. 3 (2007) 199-208 Google Scholar

  • 30. Huckstepp, R.T., id Bihi, R., Eason, R., Spyer, K.M., Dicke, N., Willecke, K., Marina, N., Gourine, A.V. and Dale, N. Connexin hemichannel-mediated CO2-dependent release of ATP in the medulla oblongata contributes to central respiratory chemosensitivity. J. Physiol. 588 (2010) 3901-3920.Google Scholar

  • 31. Giaume, C., Leybaert, L., Naus, C.C. and Sáez, J.C. Connexin and pannexin hemichannels in brain glial cells: properties, pharmacology, and roles. Front. Pharmacol. 4 (2013) 88.Google Scholar

  • 32. Iglesias, R.M., Dahl, G., Qiu, F., Spray, D.C. and Scemes, E. Pannexin 1: the molecular substrate of astrocyte "hemichannels". J. Neurosci. 29 (2009) 7092-7097.CrossrefGoogle Scholar

  • 33. Iglesias, R.M. and Spray, D.C. Pannexin1-mediated ATP release provides signal transmission between neuro2A cells. Neurochem. Res. 37 (2012) 1355-1363.CrossrefGoogle Scholar

  • 34. Orellana, J.A., Froger, N., Ezan, P., Jiang, J.X., Bennett, M.V., Naus, C.C., Giaume, C. and Sáez J.C. ATP and glutamate released via astroglial connexin 43 hemichannels mediate neuronal death through activation of pannexin 1 hemichannels. J. Neurochem. 118 (2011) 826-840.Google Scholar

  • 35. Wei, H., Deng, F., Chen, Y., Qin, Y., Hao, Y. and Guo, X. Ultrafine carbon black induces glutamate and ATP release by activating connexin and pannexin hemichannels in cultured astrocytes. Toxicology 323 (2014) 32-41.Google Scholar

  • 36. Suadicani, S.O., Brosnan, C.F. and Scemes, E. P2X7 receptors mediate ATP release and amplification of astrocytic intercellular Ca2+ signaling. J. Neurosci. 26 (2006) 1378-1385.CrossrefGoogle Scholar

  • 37. Kato, F., Kawamura, M., Shigetomi, E., Tanaka, J. and Inoue, K. ATP- and adenosine-mediated signaling in the central nervous system: synaptic purinoceptors: the stage for ATP to play its "dual-role". J. Pharmacol. Sci. 94 (2004) 107-111.CrossrefGoogle Scholar

  • 38. Choi, I.S., Cho, J.H., Lee, M.G. and Jang, I.S. Enzymatic conversion of ATP to adenosine contributes to ATP-induced inhibition of glutamate release in rat medullary dorsal horn neurons. Neuropharmacology 93 (2015) 94-102.CrossrefGoogle Scholar

  • 39. Han, T.H., Jang, S.H., Lee, S.Y. and Ryu, P.D. Adenosine reduces GABAergic IPSC frequency via presynaptic A1 receptors in hypothalamic paraventricular neurons projecting to rostral ventrolateral medulla. Neurosci. Lett. 490 (2011) 63-67.Google Scholar

  • 40. Garcia, N., Priego, M., Obis, T., Santafe, M.M., Tomàs, M., Besalduch, N., Lanuza, M.A. and Tomàs, J. Adenosine A1 and A2A receptor-mediated modulation of acetylcholine release in the mice neuromuscular junction. Eur. J. Neurosci. 38 (2013) 2229-2241.CrossrefGoogle Scholar

  • 41. Wall, M.J. and Dale, N. Auto-inhibition of rat parallel fibre-Purkinje cell synapses by activity-dependent adenosine release. J. Physiol. 581 (2007) 553-565.Google Scholar

  • 42. Cognato, G.P. and Bonan, C.D. Ectonucleotidases and Epilepsy. Open Neurosci. J. 4 (2010) 44-52. Google Scholar

  • 43. Cardoso, A.M., Schetinger, M.R., Correia-de-Sá, P. and Sévigny, J. Impact of ectonucleotidases in autonomic nervous functions. Auton. Neurosci. (2015) pii: S1566-0702(15)00051-X. DOI: 10.1016/j.autneu.2015.04.014.CrossrefGoogle Scholar

  • 44. Abbracchio, M.P. and Burnstock, G. Purinoceptors: are there families of P2X and P2Y purinoceptors? Pharmacol. Ther. 64 (1994) 445-475.CrossrefGoogle Scholar

  • 45. Fredholm, B.B., Abbracchio, M.P., Burnstock, G., Dubyak, G.R., Harden, T.K., Jacobson, K.A., Schwabe, U. and Williams, M. Towards a revised nomenclature for P1 and P2 receptors. Trends Pharmacol. Sci. 18 (1997) 79-82.CrossrefGoogle Scholar

  • 46. Ralevic, V. and Burnstock, G. Receptors for purines and pyrimidines. Pharmacol. Rev. 50 (1998) 413-492.Google Scholar

  • 47. Dubyak, G.R. Go it alone no more-P2X7 joins the society of heteromeric ATP-gated receptor channels. Mol. Pharmacol. 72 (2007) 1402-1405.CrossrefGoogle Scholar

  • 48. Burnstock, G. Physiology and pathophysiology of purinergic neurotransmission. Physiol. Rev. 87 (2007) 659-797.CrossrefGoogle Scholar

  • 49. Rubio, M.E. and Soto, F. Distinct localization of P2X receptors at excitatory postsynaptic specializations. J. Neurosci. 21 (2001) 641-653.Google Scholar

  • 50. Engel, T., Jimenez-Pacheco, A., Miras-Portugal, M.T., Diaz-Hernandez, M. and Henshall, D.C. P2X7 receptor in epilepsy; role in pathophysiology and potential targeting for seizure control. Int. J. Physiol. Pathophysiol. Pharmacol. 4 (2012) 174-187.Google Scholar

  • 51. Decker, D.A. and Galligan, J.J. Molecular mechanisms of cross-inhibition between nicotinic acetylcholine receptors and P2X receptors in myenteric neurons and HEK-293 cells. Neurogastroenterol. Motil. 22 (2010) 901-908.Google Scholar

  • 52. Shrivastava, A.N., Triller, A., Sieghart, W. and Sarto-Jackson, I. Regulation of GABAA receptor dynamics by interaction with purinergic P2X2 receptors. J. Biol. Chem. 286 (2011) 14455-14468.CrossrefGoogle Scholar

  • 53. Toulmé, E., Blais, D., Léger, C., Landry, M., Garret, M., Séguéla, P. and Boué-Grabot, E. An intracellular motif of P2X3 receptors is required for functional cross-talk with GABAA receptors in nociceptive DRG neurons. J. Neurochem. 102 (2007) 1357-1368.CrossrefGoogle Scholar

  • 54. Karanjia, R., García-Hernández, L.M., Miranda-Morales, M., Somani, N., Espinosa-Luna, R., Montaño, L.M. and Barajas-López, C. Cross-inhibitory interactions between GABAA and P2X channels in myenteric neurones. Eur. J. Neurosci. 23 (2006) 3259-3268.CrossrefGoogle Scholar

  • 55. Barajas-López, C., Montaño, L.M. and Espinosa-Luna, R. Inhibitory interactions between 5-HT3 and P2X channels in submucosal neurons. Am. J. Physiol. Gastrointest. Liver Physiol. 283 (2002) G1238-1248.Google Scholar

  • 56. Ma, B., Wynn, G., Dunn, P.M. and Burnstock, G. Increased 5-HT3-mediated signaling in pelvic afferent neurons from mice deficient in P2X2 and/or P2X3 receptor subunits. Purinergic Signal. 2 (2006) 481-489.Google Scholar

  • 57. Haydon, P.G. and Carmignoto, G. Astrocyte control of synaptic transmission and neurovascular coupling. Physiol. Rev. 86 (2006) 1009-1031.CrossrefGoogle Scholar

  • 58. Pankratov, Y., Lalo, U., Krishtal, O.A. and Verkhratsky, A. P2X receptors and synaptic plasticity. Neuroscience 158 (2009) 137-148. CrossrefGoogle Scholar

  • 59. Vavra, V., Bhattacharya, A., Jindrichova, M. and Zemkova, H. Facilitation of neurotransmitter and hormone release by P2X purinergic receptors. in: Neuroscience - Dealing With Frontiers (Contreras, C.M., Ed.), InTech, Rijeka, 2012, 61-82.Google Scholar

  • 60. Abbracchio, M.P. and Ceruti, S. Roles of P2 receptors in glial cells: focus on astrocytes. Purinergic Signal. 2 (2006) 595-604.Google Scholar

  • 61. Neary, J.T., Kang, Y., Willoughby, K.A. and Ellis, E.F. Activation of extracellular signal-regulated kinase by stretch-induced injury in astrocytes involves extracellular ATP and P2 purinergic receptors. J. Neurosci. 23 (2003) 2348-2356.Google Scholar

  • 62. Panenka, W., Jijon, H., Herx, L.M., Armstrong, J.N., Feighan, D., Wei, T., Yong, V.W., Ransohoff, R.M. and MacVicar, B.A. P2X7-like receptor activation in astrocytes increases chemokine monocyte chemoattractant protein-1 expression via mitogen-activated protein kinase. J. Neurosci. 21 (2001) 7135-7142.Google Scholar

  • 63. Franke, H., Verkhratsky, A., Burnstock, G. and Illes, P. Pathophysiology of astroglial purinergic signaling. Purinergic Signal. 8 (2012) 629-657.Google Scholar

  • 64. Skaper, S.D., Debetto, P. and Giusti, P. The P2X7 purinergic receptor: from physiology to neurological disorders. FASEB J. 24 (2010) 337-345.CrossrefGoogle Scholar

  • 65. Monif, M., Reid, C.A., Powell, K.L., Smart, M.L. and Williams, D.A. The P2X7 receptor drives microglial activation and proliferation: a trophic role for P2X7R pore. J. Neurosci. 29 (2009) 3781-3791.CrossrefGoogle Scholar

  • 66. Seo, D.R., Kim, S.Y., Kim, K.Y., Lee, H.G., Moon, J.H., Lee, J.S., Lee, S.H., Kim, S.U. and Lee Y.B. Cross talk between P2 purinergic receptors modulates extracellular ATP-mediated interleukin-10 production in rat microglial cells. Exp. Mol. Med. 40 (2008) 19-26.Google Scholar

  • 67. Ohsawa, K., Irino, Y., Nakamura, Y., Akazawa, C., Inoue, K. and Kohsaka, S. Involvement of P2X4 and P2Y12 receptors in ATP-induced microglial chemotaxis. Glia 55 (2007) 604-616.CrossrefGoogle Scholar

  • 68. Koizumi, S., Ohsawa, K., Inoue, K. and Kohsaka, S. Purinergic receptors in microglia: Functional modal shifts of microglia mediated by P2 and P1 receptors. Glia 61 (2013) 47-54.CrossrefGoogle Scholar

  • 69. Choi, H.B., Ryu, J.K., Kim, S.U. and McLarnon, J.G. Modulation of the purinergic P2X7 receptor attenuates lipopolysaccharide-mediated microglial activation and neuronal damage in inflamed brain. J. Neurosci. 27 (2007) 4957-4968.CrossrefGoogle Scholar

  • 70. Agresti, C., Meomartini, M.E., Amadio, S., Ambrosini, E., Serafini, B., Franchini, L., Volonté, C., Aloisi, F. and Visentin, S. Metabotropic P2 receptor activation regulates oligodendrocyte progenitor migration and development. Glia 50 (2005) 132-144.CrossrefGoogle Scholar

  • 71. Faroni, A., Smith, R.J.P., Procacci, P., Castelnovo, L.F., Puccianti, E., Reid, A.J., Magnaghi, V. and Verkhratsky, A. Purinergic signaling mediated by P2X7 receptors controls myelination in sciatic nerves. J. Neurosci. Res. 92 (2014) 1259-1269. CrossrefGoogle Scholar

  • 72. Song, X.M., Xu, X.H., Zhu, J., Guo, Z., Li, J., He, C., Burnstock, G., Yuan, H. and Xiang, Z. Up-regulation of P2X7 receptors mediating proliferation of Schwann cells after sciatic nerve injury. Purinergic Signal. 11 (2015) 203-213.Google Scholar

  • 73. Luo, J., Lee, S., Wu, D., Yeh, J., Ellamushi, H., Wheeler, A.P., Warnes, G., Zhang, Y. and Bo, X. P2X7 purinoceptors contribute to the death of Schwann cells transplanted into the spinal cord. Cell Death Dis. 4 (2013) e829.Google Scholar

  • 74. Feng, J.F., Gao, X.F., Pu, Y.Y., Burnstock, G., Xiang, Z. and He, C. P2X7 receptors and Fyn kinase mediate ATP-induced oligodendrocyte progenitor cell migration. Purinergic Signal. 11 (2015) 361-369.Google Scholar

  • 75. Inoue, K. and Tsuda, M. Purinergic systems, neuropathic pain and the role of microglia. Exp. Neurol. 234 (2012) 293-301.Google Scholar

  • 76. Tsuda, M., Tozaki-Saitoh, H. and Inoue, K. P2X4R and P2X7R in neuropathic pain. WIREs Membr. Transp. Signal. 1 (2012 ) 513-521.Google Scholar

  • 77. Burnstock, G. An introduction to the roles of purinergic signaling in neurodegeneration, neuroprotection and neuroregeneration. Neuropharmacology (2015) pii: S0028-3908(15)00212-9. DOI: 10.1016/j.neuropharm.2015.05.031.CrossrefGoogle Scholar

  • 78. Ulrich, H., Abbracchio, M.P. and Burnstock, G. Extrinsic purinergic regulation of neural stem/progenitor cells: implications for CNS development and repair. Stem Cell Rev. 8 (2012) 755-767.CrossrefGoogle Scholar

  • 79. Zemková, H., Balík, A., Jindrichová, M. and Vávra, V. Molecular structure of purinergic P2X receptors and their expression in the hypothalamus and pituitary. Physiol. Res. 57 (2008) 23-38.Google Scholar

  • 80. North, R.A. Molecular physiology of P2X receptors. Physiol. Rev. 82 (2002) 1013-1067.CrossrefGoogle Scholar

  • 81. Burnstock, G. Purine and pyrimidine receptors. Cell. Mol. Life Sci. 64 (2007) 1471-1483.CrossrefGoogle Scholar

  • 82. Habermacher, C., Dunning, K., Chataigneau, T. and Grutter, T. Molecular structure and function of P2X receptors. Neuropharmacology (2015) pii: S0028-3908(15)30039-3. DOI: 10.1016/j.neuropharm.2015.07.032.CrossrefGoogle Scholar

  • 83. Dal Ben, D., Buccioni, M., Lambertucci, C., Marucci, G., Thomas, A. and Volpini, R. Purinergic P2X receptors: structural models and analysis of ligand-target interaction. Eur. J. Med. Chem. 89 (2015) 561-580.Google Scholar

  • 84. Alves, L.A., da Silva, J.H., Ferreira, D.N., Fidalgo-Neto, A.A., Teixeira, P.C., de Souza, C.A., Caffarena, E.R. and de Freitas, M.S. Structural and molecular modeling features of P2X receptors. Int. J. Mol. Sci. 15 (2014) 4531-4549.CrossrefGoogle Scholar

  • 85. Wang, L., Feng, D., Yan, H., Wang, Z. and Pei, L. Comparative analysis of P2X1, P2X2, P2X3, and P2X4 receptor subunits in rat nodose ganglion neurons. PLoS One 9 (2014) e96699.Google Scholar

  • 86. Kuroda, H., Shibukawa, Y., Soya, M., Masamura, A., Kasahara, M., Tazaki, M. and Ichinohe, T. Expression of P2X1 and P2X4 receptors in rat trigeminal ganglion neurons. Neuroreport. 23 (2012) 752-756. CrossrefGoogle Scholar

  • 87. Illes, P. and Ribeiro, A.J. Molecular physiology of P2 receptors in the central nervous system. Eur. J. Pharmacol. 483 (2004) 5-17.Google Scholar

  • 88. Collo, G., North, R.A., Kawashima, E., Merlo-Pich, E., Neidhart, S., Surprenant, A. and Buell, G. Cloning of P2X5 and P2X6 receptors and the distribution and properties of an extended family of ATP-gated ion channels. J. Neurosci. 16 (1996) 2495-2507.Google Scholar

  • 89. Kobayashi, K., Yamanaka, H. and Noguchi, K. Expression of ATP receptors in the rat dorsal root ganglion and spinal cord. Anat. Sci. Int. 88 (2013) 10-16.CrossrefGoogle Scholar

  • 90. Mo, G., Bernier, L.P., Zhao, Q., Chabot-Doré, A.J., Ase, A.R., Logothetis, D., Cao, C.Q. and Séguéla, P. Subtype-specific regulation of P2X3 and P2X2/3 receptors by phosphoinositides in peripheral nociceptors. Mol. Pain 5 (2009) 47.CrossrefGoogle Scholar

  • 91. Xiang, Z., Bo, X. and Burnstock, G. Localization of ATP-gated P2X receptor immunoreactivity in rat sensory and sympathetic ganglia. Neurosci. Lett. 256 (1998) 105-108.CrossrefGoogle Scholar

  • 92. Fischer, W., Appelt, K., Grohmann, M., Franke, H., Nörenberg, W. and Illes, P. Increase of intracellular Ca2+ by P2X and P2Y receptor-subtypes in cultured cortical astroglia of the rat. Neuroscience 160 (2009) 767-783.CrossrefGoogle Scholar

  • 93. Coddou, C., Yan, Z., Obsil, T., Huidobro-Toro, J.P. and Stojilkovic, S.S. Activation and regulation of purinergic P2X receptor channels. Pharmacol. Rev. 63 (2011) 641-683.CrossrefGoogle Scholar

  • 94. Decker, D.A. and Galligan, J.J. Cross-inhibition between nicotinic acetylcholine receptors and P2X receptors in myenteric neurons and HEK-293 cells. Am. J. Physiol. Gastrointest. Liver Physiol. 296 (2009) G1267-1276.Google Scholar

  • 95. Limapichat, W., Dougherty, D.A. and Lester, H.A. Subtype-specific mechanisms for functional interaction between α6β4* nicotinic acetylcholine receptors and P2X receptors. Mol. Pharmacol. 86 (2014) 263-274.CrossrefGoogle Scholar

  • 96. Sokolova, E., Nistri, A. and Giniatullin, R. Negative cross talk between anionic GABAA and cationic P2X ionotropic receptors of rat dorsal root ganglion neurons. J. Neurosci. 21 (2001) 4958-4968.Google Scholar

  • 97. Xu, X.J., Boumechache, M., Robinson, L.E., Marschall, V., Gorecki, D.C., Masin, M. and Murrell-Lagnado, R.D. Splice variants of the P2X7 receptor reveal differential agonist dependence and functional coupling with pannexin-1. J. Cell Sci. 125 (2012) 3776-3789.Google Scholar

  • 98. Nicke, A. Homotrimeric complexes are the dominant assembly state of native P2X7 subunits. Biochem. Biophys. Res. Commun. 377 (2008) 803-808.Google Scholar

  • 99. Qu, Y., Misaghi, S., Newton, K., Gilmour, L.L., Louie, S., Cupp, J.E., Dubyak, G.R., Hackos, D. and Dixit, V.M. Pannexin-1 is required for ATP release during apoptosis but not for inflammasome activation. J. Immunol. 186 (2011) 6553-6561.Google Scholar

  • 100. Domercq, M., Vázquez-Villoldo, N. and Matute, C. Neurotransmitter signaling in the pathophysiology of microglia. Front. Cell. Neurosci. 7 (2013) 49. Google Scholar

  • 101. Communi, D., Gonzalez, N.S., Detheux, M., Brézillon, S., Lannoy, V., Parmentier, M. and Boeynaems, J.M. Identification of a novel human ADP receptor coupled to Gi. J. Biol. Chem. 276 (2001) 41479-41485.Google Scholar

  • 102. Guzman, S.J., Schmidt, H., Franke, H., Krügel, U., Eilers, J., Illes, P. and Gerevich, Z. P2Y1 receptors inhibit long-term depression in the prefrontal cortex. Neuropharmacology 59 (2010) 406-415.CrossrefGoogle Scholar

  • 103. Moriyama, T., Iida, T., Kobayashi, K., Higashi, T., Fukuoka, T., Tsumura, H., Leon, C., Suzuki, N., Inoue, K., Gachet, C., Noguchi, K. and Tominaga, M. Possible involvement of P2Y2 metabotropic receptors in ATP-induced transient receptor potential vanilloid receptor 1-mediated thermal hypersensitivity. J. Neurosci. 23 (2003) 6058-6062.Google Scholar

  • 104. Yoshioka, K., Hosoda, R., Kuroda, Y. and Nakata, H. Heterooligomerization of adenosine A1 receptors with P2Y1 receptors in rat brains. FEBS Lett. 531 (2002) 299-303.Google Scholar

  • 105. Yoshioka, K. and Nakata, H. ATP- and adenosine-mediated signaling in the central nervous system: purinergic receptor complex: generating adenine nucleotide-sensitive adenosine receptors. J. Pharmacol. Sci. 94 (2004) 88-94.CrossrefGoogle Scholar

  • 106. Yoshioka, K., Saitoh, O. and Nakata, H. Heteromeric association creates a P2Ylike adenosine receptor. Proc. Natl. Acad. Sci. U.S.A. 98 (2001) 7617-7622.CrossrefGoogle Scholar

  • 107. Scemes, E. and Giaume, C. Astrocyte calcium waves: what they are and what they do. Glia 54 (2006) 716-725.CrossrefGoogle Scholar

  • 108. Haynes, S.E., Hollopeter, G., Yang, G., Kurpius, D., Dailey, M.E., Gan, W.B. and Julius, D. The P2Y12 receptor regulates microglial activation by extracellular nucleotides. Nat. Neurosci. 9 (2006) 1512-1519.CrossrefGoogle Scholar

  • 109. Ohsawa, K., Irino, Y., Sanagi, T., Nakamura, Y., Suzuki, E., Inoue, K. and Kohsaka, S. P2Y12 receptor-mediated integrin-β1 activation regulates microglial process extension induced by ATP. Glia 58 (2010) 790-801.Google Scholar

  • 110. Koizumi, S., Shigemoto-Mogami, Y., Nasu-Tada, K., Shinozaki, Y., Ohsawa, K., Tsuda, M., Joshi, B.V., Jacobson, K.A., Kohsaka, S. and Inoue, K. UDP acting at P2Y6 receptors is a mediator of microglial phagocytosis. Nature 446 (2007) 1091-1095.Google Scholar

  • 111. Franke, H., Krügel, U., Grosche, J., Heine, C., Härtig, W., Allgaier, C. and Illes, P. P2Y receptor expression on astrocytes in the nucleus accumbens of rats. Neuroscience 127 (2004) 431-441.CrossrefGoogle Scholar

  • 112. Washburn, K.B. and Neary, J.T. P2 purinergic receptors signal to STAT3 in astrocytes: Difference in STAT3 responses to P2Y and P2X receptor activation. Neuroscience 142 (2006) 411-423.CrossrefGoogle Scholar

  • 113. Malin, S.A. and Molliver, D.C. Gi- and Gq-coupled ADP (P2Y) receptors act in opposition to modulate nociceptive signaling and inflammatory pain behavior. Mol. Pain 6 (2010) 21.CrossrefGoogle Scholar

  • 114. Jacobson, K.A., Paoletta, S., Katritch, V., Wu, B., Gao, Z.G., Zhao, Q., Stevens, R.C. and Kiselev, E. Nucleotides acting at P2Y receptors: connecting structure and function. Mol. Pharmacol. 88 (2015) 220-230. CrossrefGoogle Scholar

  • 115. Jacobson, K.A. P2X and P2Y receptors. Tocris Bioscience Scientific Review Series 33 (2010) 1-15.Google Scholar

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

  • 117. Chambers, J.K., Macdonald, L.E., Sarau, H.M., Ames, R.S., Freeman, K., Foley, J.J., Zhu, Y., McLaughlin, M.M., Murdock, P., McMillan, L., Trill, J., Swift, A., Aiyar, N., Taylor, P., Vawter, L., Naheed, S., Szekeres, P., Hervieu, G., Scott, C., Watson, J.M., Murphy, A.J., Duzic, E., Klein, C., Bergsma, D.J., Wilson, S. and Livi, G.P. A G protein-coupled receptor for UDP-glucose. J. Biol. Chem. 275 (2000) 10767-10771.CrossrefGoogle Scholar

  • 118. Moore, D.J., Chambers, J.K., Wahlin, J.P., Tan, K.B., Moore, G.B., Jenkins, O., Emson, P.C. and Murdock, P.R. Expression pattern of human P2Y receptor subtypes: a quantitative reverse transcription-polymerase chain reaction study. Biochim. Biophys. Acta 1521 (2001) 107-119.Google Scholar

  • 119. Zhang, F.L., Luo, L., Gustafson, E., Palmer, K., Qiao, X., Fan, X., Yang, S., Laz, T.M., Bayne and Monsma, Jr. F.M. P2Y13: identification and characterization of a novel Gαi-coupled ADP receptor from human and mouse. J. Pharmacol. Exp. Ther. 301 (2002) 705-713.Google Scholar

  • 120. Moore, D.J., Murdock, P.R., Watson, J.M., Faull, R.L., Waldvogel, H.J., Szekeres, P.G., Wilson, S., Freeman, K.B. and Emson, P.C. 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 (2003) 10-23.CrossrefGoogle Scholar

  • 121. Amadio, S., Vacca, F., Martorana, A., Sancesario, G. and Volonté, C. P2Y1 receptor switches to neurons from glia in juvenile versus neonatal rat cerebellar cortex. BMC Dev. Biol. 7 (2007) 77.CrossrefGoogle Scholar

  • 122. Fong, A.Y., Krstew, E.V., Barden, J. and Lawrence, A.J. Immunoreactive localisation of P2Y1 receptors within the rat and human nodose ganglia and rat brainstem: comparison with [α33P]deoxyadenosine 5’-triphosphate autoradiography. Neuroscience 113 (2002) 809-823.CrossrefGoogle Scholar

  • 123. Ruan, H.Z. and Burnstock, G. Localisation of P2Y1 and P2Y4 receptors in dorsal root, nodose and trigeminal ganglia of the rat. Histochem. Cell Biol. 120 (2003) 415-426.CrossrefGoogle Scholar

  • 124. Volonté, C., Amadio, S., D’Ambrosi, N., Colpi, M., and Burnstock, G. P2 receptor web: complexity and fine-tuning. Pharmacol. Ther. 112 (2006) 264-280.CrossrefGoogle Scholar

  • 125. Costanzi, S., Mamedova, L., Gao, Z.G., and Jacobson, K.A. Architecture of P2Y nucleotide receptors: structural comparison based on sequence analysis, mutagenesis, and homology modeling. J. Med. Chem. 47 (2004) 5393-5404.CrossrefGoogle Scholar

  • 126. Tonazzini, I., Trincavelli, M.L., Storm-Mathisen, J., Martini, C. and Bergersen, L.H. Colocalization and functional cross-talk between A1 and P2Y1 purine receptors in rat hippocampus. Eur. J. Neurosci. 26 (2007) 890-902.CrossrefGoogle Scholar

  • 127. Tonazzini, I., Trincavelli, M.L., Montali, M. and Martini, C. Regulation of A1 adenosine receptor functioning induced by P2Y1 purinergic receptor activation in human astroglial cells. J. Neurosci. Res. 86 (2008) 2857-2866.CrossrefGoogle Scholar

  • 128. Suzuki, T., Namba, K., Tsuga, H. and Nakata, H. Regulation of pharmacology by hetero-oligomerization between A1 adenosine receptor and P2Y2 receptor. Biochem. Biophys. Res. Commun. 351 (2006) 559-565.Google Scholar

  • 129. Namba, K., Suzuki, T. and Nakata H. Immunogold electron microscopic evidence of in situ formation of homo- and heteromeric purinergic adenosine A1 and P2Y2 receptors in rat brain. BMC Res. Notes 3 (2010) 323.CrossrefGoogle Scholar

  • 130. Ecke, D., Hanck, T., Tulapurkar, M.E., Schäfer, R., Kassack, M., Stricker, R. and Reiser, G. Hetero-oligomerization of the P2Y11 receptor with the P2Y1 receptor controls the internalization and ligand selectivity of the P2Y11 receptor. Biochem. J. 409 (2008) 107-116.Google Scholar

  • 131. Kwon, S.G., Roh, D.H., Yoon, S.Y., Moon, J.Y., Choi, S.R., Choi, H.S., Kang, S.Y., Han, H.J., Beitz, A.J. and Lee, J.H. Blockade of peripheral P2Y1 receptors prevents the induction of thermal hyperalgesia via modulation of TRPV1 expression in carrageenan-induced inflammatory pain rats: involvement of p38 MAPK phosphorylation in DRGs. Neuropharmacology 79 (2014) 368-79.CrossrefGoogle Scholar

  • 132. Wang, H., Wang, D.H. and Galligan, J.J. P2Y2 receptors mediate ATPinduced resensitization of TRPV1 expressed by kidney projecting sensory neurons. Am. J. Physiol. Regul. Integr. Comp. Physiol. 298 (2010) R1634-1641.Google Scholar

  • 133. Burnstock, G. Introduction to purinergic signaling in the brain. Adv. Exp. Med. Biol. 986 (2013) 1-12.Google Scholar

  • 134. Ota, Y., Zanetti, A.T. and Hallock, R.M. The role of astrocytes in the regulation of synaptic plasticity and memory formation. Neural. Plast. 2013 (2013) 185463.Google Scholar

  • 135. Illes, P. and Ribeiro, J.A. Neuronal P2 receptors of the central nervous system. Curr. Top. Med. Chem. 4 (2004) 831-838.CrossrefGoogle Scholar

  • 136. Lalo, U., Palygin, O., Rasooli-Nejad, S., Andrew, J., Haydon, P.G. and Pankratov, Y. Exocytosis of ATP from astrocytes modulates phasic and tonic inhibition in the neocortex. PLoS Biol. 12 (2014) e1001747.CrossrefGoogle Scholar

  • 137. Ferreira-Neto, H.C., Yao, S.T. and Antunes, V.R. Purinergic and glutamatergic interactions in the hypothalamic paraventricular nucleus modulate sympathetic outflow. Purinergic Signal. 9 (2013) 337-349.Google Scholar

  • 138. Burnstock, G. Introduction and perspective, historical note. Front. Cell. Neurosci. 7 (2013) 227.Google Scholar

  • 139. Toulme, E. and Khakh, B.S. Imaging P2X4 receptor lateral mobility in microglia: regulation by calcium and p38 MAPK. J. Biol. Chem. 287 (2012) 14734-14748. Google Scholar

  • 140. Davalos, D., Grutzendler, J., Yang, G., Kim, J.V., Zuo, Y., Jung, S., Littman, D.R., Dustin, M.L. and Gan, W-B. ATP mediates rapid microglial response to local brain injury in vivo. Nat. Neurosci. 8 (2005) 752-758.CrossrefGoogle Scholar

  • 141. Wake, H., Moorhouse, A.J., Jinno, S., Kohsaka, S., Nabekura, J. Resting microglia directly monitor the functional state of synapses in vivo and determine the fate of ischemic terminals. J. Neurosci. 29 (2009) 3974-3980.CrossrefGoogle Scholar

  • 142. Pascual, O., Ben Achour, S., Rostaing, P., Triller, A. and Bessis, A. Microglia activation triggers astrocyte-mediated modulation of excitatory neurotransmission. Proc. Natl. Acad. Sci. U.S.A. 109 (2012) E197-205.CrossrefGoogle Scholar

  • 143. Trang, T., Beggs, S. and Saltera M.W. Brain-derived neurotrophic factor from microglia: a molecular substrate for neuropathic pain. Neuron Glia Biol. 7 (2011) 99-108.CrossrefGoogle Scholar

  • 144. Morioka, N., Tokuhara, M., Harano, S., Nakamura, Y., Hisaoka-Nakashima, K. and Nakata, Y. The activation of P2Y6 receptor in cultured spinal microglia induces the production of CCL2 through the MAP kinases-NF-κB pathway. Neuropharmacology 75 (2013) 116-125.CrossrefGoogle Scholar

  • 145. Verkhratsky, A., Pankratov, Y., Lalo, U. and Nedergaard, M. P2X receptors in neuroglia. Wiley Interdiscip. Rev. Membr. Transp. Signal. 1 (2012) 151-161.CrossrefGoogle Scholar

  • 146. Li F, Wang L, Li JW, Gong, M., He, L., Feng, R., Dai, Z. and Li, S-Q. Hypoxia induced amoeboid microglial cell activation in postnatal rat brain is mediated by ATP receptor P2X4. BMC Neurosci. 12 (2011) 111.CrossrefGoogle Scholar

  • 147. Inoue, K. UDP facilitates microglial phagocytosis through P2Y6 receptors. Cell Adh. Migr. 1 (2007) 131-132.Google Scholar

  • 148. Webster, C.M., Hokari, M., McManus, A., Tang, X.N., Ma, H., Kacimi, R. and Yenari, M.A. Microglial P2Y12 deficiency/inhibition protects against brain ischemia. PLoS One 8 (2013) e70927.Google Scholar

  • 149. Ferreira, R. and Schlichter, L.C. Selective activation of KCa3.1 and CRAC channels by P2Y2 receptors promotes Ca2+ signaling, store refilling and migration of rat microglial cells. PLoS One 8 (2013) e62345.Google Scholar

  • 150. Carroll, W.A., Donnelly-Roberts, D. and Jarvis, M.F.. Selective P2X7 receptor antagonists for chronic inflammation and pain. Purinergic Signal. 5 (2009) 63-73.Google Scholar

  • 151. Bartlett, R., Yerbury, J.J. and Sluyter, R. P2X7 receptor activation induces reactive oxygen species formation and cell death in murine EOC13 microglia. Mediat. Inflamm. 2013 (2013) 271813.Google Scholar

  • 152. Friedle, S.A., Brautigam, V.M., Nikodemova, M., Wright, M.L. and Watters, J.J. The P2X7-Egr pathway regulates nucleotide-dependent inflammatory gene expression in microglia. Glia 59 (2011) 1-13.CrossrefGoogle Scholar

  • 153. Mead, E.L., Mosley, A., Eaton, S., Dobson, L., Heales, S.J. and Pocock, J.M. Microglial neurotransmitter receptors trigger superoxide production in microglia; consequences for microglial-neuronal interactions. J. Neurochem. 121 (2012) 287-301.CrossrefGoogle Scholar

  • 154. Smith, S.M., Mitchell, G.S., Friedle, S.A., Sibigtroth, C.M., Vinit, S. and Watters, J.J. Hypoxia attenuates purinergic P2X receptor-induced inflammatory gene expression in brainstem microglia. Hypoxia (Auckl) 1 (2013). DOI: 10.2147/HP.S45529.CrossrefGoogle Scholar

  • 155. Inoue, K., Koizumi, S., Kataoka, A., Tozaki-Saitoh, H. and Tsuda, M. P2Y6- evoked microglial phagocytosis. Int. Rev. Neurobiol. 85 (2009) 159-163.CrossrefGoogle Scholar

  • 156. Neher, J.J., Neniskyte, U., Hornik, T. and Brown, G.C. Inhibition of UDP/P2Y6 purinergic signaling prevents phagocytosis of viable neurons by activated microglia in vitro and in vivo. Glia 62 (2014) 1463-1475.CrossrefGoogle Scholar

  • 157. Bulavina, L., Szulzewsky, F., Rocha, A., Krabbe, G., Robson, S.C., Matyash, V. and Kettenmann, H. NTPDase1 activity attenuates microglial phagocytosis. Purinergic Signal. 9 (2013) 199-205.Google Scholar

  • 158. Zabłocka, A. and Janusz, M. The structure and function of central nervous system. Postepy Hig. Med. Dosw. 61 (2007) 454-460.Google Scholar

  • 159. Vijayaraghavan, S. Glial-neuronal interactions-implications for plasticity and drug addiction. AAPS J. 11 (2009) 123-132.CrossrefGoogle Scholar

  • 160. Fellin, T., Pascual, O. and Haydona, P.G. Astrocytes coordinate synaptic networks: balanced excitation and inhibition. Physiology (Bethesda) 21 (2006) 208-215.CrossrefGoogle Scholar

  • 161. Accorsi-Mendonça, D., Zoccal, D.B., Bonagamba, L.G. and Machado, B.H. Glial cells modulate the synaptic transmission of NTS neurons sending projections to ventral medulla of Wistar rats. Physiol. Rep. 1 (2013) e00080.Google Scholar

  • 162. Bhattacharya, A., Vavra, V., Svobodova, I., Bendova, Z., Vereb, G. and Zemkova, H. Potentiation of inhibitory synaptic transmission by extracellular ATP in rat suprachiasmatic nuclei. J. Neurosci. 33 (2013) 8035-8044.CrossrefGoogle Scholar

  • 163. Vavra, V., Bhattacharya, A. and Zemkova, H. Facilitation of glutamate and GABA release by P2X receptor activation in supraoptic neurons from freshly isolated rat brain slices. Neuroscience 188 (2011) 1-12.CrossrefGoogle Scholar

  • 164. Fam, S.R., Gallagher, C.J., Kalia, L.V. and Salter, M.W. Differential frequency dependence of P2Y1- and P2Y2-mediated Ca2+ signaling in astrocytes. J. Neurosci. 23 (2003) 4437-4444.Google Scholar

  • 165. D’Alimonte, I., Ciccarelli, R., Di Iorio, P., Nargi, E., Buccella, S., Giuliani, P., Rathbone, M.P., Jiang, S., Caciagli, F. and Ballerini, P. Activation of P2X7 receptors stimulates the expression of P2Y2 receptor mRNA in astrocytes cultured from rat brain. Int. J. Immunopathol. Pharmacol. 20 (2007) 301-316.Google Scholar

  • 166. Lalo, U., Andrew, J., Palygin, O. and Pankratov, Y. Ca2+-dependent modulation of GABAA and NMDA receptors by extracellular ATP: implication for function of tripartite synapse. Biochem. Soc. T. 37 (2009) 1407-1411.CrossrefGoogle Scholar

  • 167. Palygin, O., Lalo, U., Verkhratsky, A. and Pankratov, Y. Ionotropic NMDA and P2X1/5 receptors mediate synaptically induced Ca2+ signaling in cortical astrocytes. Cell Calcium 48 (2010) 225-231.CrossrefGoogle Scholar

  • 168. Cho, J.H., Choi, I.S. and Jang, I.S. P2X7 receptors enhance glutamate release in hippocampal hilar neurons. Neuroreport 21 (2010) 865-870. CrossrefGoogle Scholar

  • 169. Chen, J., Tan, Z., Zeng, L., Zhang, X., He, Y., Gao, W., Wu, X., Li, Y., Bu, B., Wang, W. and Duan, S. Heterosynaptic long-term depression mediated by ATP released from astrocytes. Glia 61 (2013) 178-191.CrossrefGoogle Scholar

  • 170. da Silva, B.M., de Mendonça, A. and Ribeiro, J.A. Long-term depression is not modulated by ATP receptors in the rat CA1 hippocampal region. Neurosci. Lett. 383 (2005) 345-349.Google Scholar

  • 171. Wang, X., Lou, N., Xu, Q., Tian, G.F., Peng, W.G., Han, X., Kang, J., Takano, T. and Nedergaard, M. Astrocytic Ca2+ signaling evoked by sensory stimulation in vivo. Nat. Neurosci. 9 (2006) 816-823.CrossrefGoogle Scholar

  • 172. Franke, H. and Illes, P. Nucleotide signaling in astrogliosis. Neurosci. Lett. 565 (2014) 14-22.Google Scholar

  • 173. Quintas, C., Pinho, D., Pereira, C., Saraiva, L., Gonçalves, J. and Queiroz, G. Microglia P2Y6 receptors mediate nitric oxide release and astrocyte apoptosis. J. Neuroinflammation 11 (2014) 141.CrossrefGoogle Scholar

  • 174. Weisman, G.A., Wang, M., Kong, Q., Chorna, N.E., Neary, J.T., Sun, G.Y., González, F.A., Seye, C.I. and Erb, L. Molecular determinants of P2Y2 nucleotide receptor function: implications for proliferative and inflammatory pathways in astrocytes. Mol. Neurobiol. 31 (2005) 169-183.CrossrefGoogle Scholar

  • 175. Wang, M., Kong, Q., Gonzalez, F.A., Sun, G., Erb, L., Seye, C. and Weisman, G.A. P2Y2 nucleotide receptor interaction with αv integrin mediates astrocyte migration. J. Neurochem. 95 (2005) 630-640.CrossrefGoogle Scholar

  • 176. McCullough, L., Wu, L., Haughey, N., Liang, X., Hand, T., Wang, Q., Breyer and R.M., Andreasson, K. Neuroprotective function of the PGE2 EP2 receptor in cerebral ischemia. J. Neurosci. 24 (2004) 257-268.CrossrefGoogle Scholar

  • 177. Fujita, T., Tozaki-Saitoh, H. and Inoue, K. P2Y1 receptor signaling enhances neuroprotection by astrocytes against oxidative stress via IL-6 release in hippocampal cultures. Glia 57 (2009) 244-257.CrossrefGoogle Scholar

  • 178. Shinozaki, Y., Koizumi, S., Ohno, Y., Nagao, T. and Inoue, K. Extracellular ATP counteracts the ERK1/2-mediated death-promoting signaling cascades in astrocytes. Glia 54 (2006) 606-618.CrossrefGoogle Scholar

  • 179. Kim, B., Jeong, H.K., Kim, J.H., Lee, S.Y., Jou, I. and Joe, E.H. Uridine 5’- diphosphate induces chemokine expression in microglia and astrocytes through activation of the P2Y6 receptor. J. Immunol. 186 (2011) 3701-3709.CrossrefGoogle Scholar

  • 180. Barbieri, R., Alloisio, S., Ferroni, S. and Nobile, M. Differential crosstalk between P2X7 and arachidonic acid in activation of mitogen-activated protein kinases. Neurochem. Int. 53 (2008) 255-262.CrossrefGoogle Scholar

  • 181. Narcisse, L., Scemes, E., Zhao, Y., Lee, S.C. and Brosnan, C.F. The cytokine IL-1β transiently enhances P2X7 receptor expression and function in human astrocytes. Glia 49 (2005) 245-258.CrossrefGoogle Scholar

  • 182. John, G.R., Simpson, J.E., Woodroofe, M.N., Lee, S.C. and Brosnan, C.F. Extracellular nucleotides differentially regulate interleukin-1β signaling in primary human astrocytes: implications for inflammatory gene expression. J. Neurosci. 21 (2001) 4134-4142. Google Scholar

  • 183. Sun, W., McConnell, E., Pare, J.F., Xu, Q., Chen, M., Peng, W., Lovatt, D., Han, X., Smith Y. and Nedergaard, M. Glutamate-dependent neuroglial calcium signaling differs between young and adult brain. Science 339 (2013) 197-200.Google Scholar

  • 184. Otsu, Y., Couchman, K., Lyons, D.G., Collot, M., Agarwal, A., Mallet, J.M., Pfrieger, F.W., Bergles, D.E. and Charpak, S. Calcium dynamics in astrocyte processes during neurovascular coupling. Nat. Neurosci. 18 (2015) 210-218.Google Scholar

  • 185. Hashioka, S., Wang, Y.F., Little, J.P., Choi, H.B., Klegeris, A., McGeer, P.L. and McLarnon, J.G. Purinergic responses of calcium-dependent signaling pathways in cultured adult human astrocytes. BMC Neurosci. 15 (2014) 18.CrossrefGoogle Scholar

  • 186. Stevens, B., Porta, S., Haak, L.L., Gallo, V. and Fields, R.D. Adenosine: a neuron-glial transmitter promoting myelination in the CNS in response to action potentials. Neuron 36 (2002) 855-868.CrossrefGoogle Scholar

  • 187. Ishibashi, T., Dakin, K.A., Stevens, B., Lee, P.R., Kozlov, S.V., Stewart, C.L. and Fields, R.D. Astrocytes promote myelination in response to electrical impulses. Neuron 49 (2006) 823-832.CrossrefGoogle Scholar

  • 188. Fields, R.D. Nerve impulses regulate myelination through purinergic signaling. Novart. Fdn. Symp. 276 (2006) 148-158.CrossrefGoogle Scholar

  • 189. Ceruti, S., Viganò, F., Boda, E., Ferrario, S., Magni, G., Boccazzi, M., Rosa, P., Buffo, A. and Abbracchio, M.P. Expression of the new P2Y-like receptor GPR17 during oligodendrocyte precursor cell maturation regulates sensitivity to ATP-induced death. Glia 59 (2011) 363-378.CrossrefGoogle Scholar

  • 190. Lin, J.H., Takano, T., Arcuino, G., Wang, X., Hu, F., Darzynkiewicz, Z., Nunes, M., Goldman, S.A. and Nedergaard, M. Purinergic signaling regulates neural progenitor cell expansion and neurogenesis. Dev. Biol. 302 (2007) 356-366.CrossrefGoogle Scholar

  • 191. Lecca, D., Trincavelli, M.L., Gelosa, P., Sironi, L., Ciana, P., Fumagalli, M., Villa, G., Verderio, C., Grumelli, C., Guerrini, U., Tremoli, E., Rosa, P., Cuboni, S., Martini, C., Buffo, A., Cimino, M. and Abbracchio M.P. The recently identified P2Y-like receptor GPR17 is a sensor of brain damage and a new target for brain repair. PLoS One 3 (2008) e3579. Google Scholar

About the article

Received: 2015-05-08

Accepted: 2015-10-29

Published Online: 2016-03-05

Published in Print: 2015-12-01

Citation Information: Cellular and Molecular Biology Letters, Volume 20, Issue 5, Pages 867–918, ISSN (Online) 1689-1392, DOI: https://doi.org/10.1515/cmble-2015-0050.

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