Table of Contents
Cardiovascular Psychiatry and Neurology
Volume 2009, Article ID 861324, 13 pages
http://dx.doi.org/10.1155/2009/861324
Review Article

P2 X 7 Receptors in Neurological and Cardiovascular Disorders

Department of Pharmacology and Anesthesiology, University of Padova, Largo “E. Meneghetti” 2, 35131 Padova, Italy

Received 7 April 2009; Revised 26 April 2009; Accepted 27 April 2009

Academic Editor: Gjumrakch Aliev

Copyright © 2009 Stephen D. Skaper et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. W. S. T. Griffin, J. G. Sheng, M. C. Royston et al., “Glial-neuronal interactions in Alzheimer's disease: the potential role of a ‘cytokine cycle’ in disease progression,” Brain Pathology, vol. 8, no. 1, pp. 65–72, 1998. View at Google Scholar
  2. J. M. Craft, D. M. Watterson, and L. J. van Eldik, “Neuroinflammation: a potential therapeutic target,” Expert Opinion on Therapeutic Targets, vol. 9, no. 5, pp. 887–900, 2005. View at Publisher · View at Google Scholar · View at PubMed
  3. P. L. McGeer, M. Schulzer, and E. G. McGeer, “Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer's disease: a review of 17 epidemiologic studies,” Neurology, vol. 47, no. 2, pp. 425–432, 1996. View at Google Scholar
  4. P. L. McGeer and E. G. McGeer, “Polymorphisms in inflammatory genes and the risk of Alzheimer disease,” Archives of Neurology, vol. 58, no. 11, pp. 1790–1792, 2001. View at Publisher · View at Google Scholar
  5. P. Eikelenboom and W. A. van Gool, “Neuroinflammatory perspectives on the two faces of Alzheimer's disease,” Journal of Neural Transmission, vol. 111, no. 3, pp. 281–294, 2004. View at Publisher · View at Google Scholar · View at PubMed
  6. P. L. McGeer and E. G. McGeer, “Inflammation and the degenerative diseases of aging,” Annals of the New York Academy of Sciences, vol. 1035, pp. 104–116, 2004. View at Publisher · View at Google Scholar · View at PubMed
  7. D. Langford and E. Masliah, “Crosstalk between components of the blood brain barrier and cells of the CNS in microglial activation in AIDS,” Brain Pathology, vol. 11, no. 3, pp. 306–312, 2001. View at Google Scholar
  8. V. H. Perry, C. Cunningham, and D. Boche, “Atypical inflammation in the central nervous system in prion disease,” Current Opinion in Neurology, vol. 15, no. 3, pp. 349–354, 2002. View at Publisher · View at Google Scholar
  9. P. Teismann and J. B. Schulz, “Cellular pathology of Parkinson's disease: astrocytes, microglia and inflammation,” Cell and Tissue Research, vol. 318, no. 1, pp. 149–161, 2004. View at Publisher · View at Google Scholar · View at PubMed
  10. G. H. Danton and W. D. Dietrich, “Inflammatory mechanisms after ischemia and stroke,” Journal of Neuropathology and Experimental Neurology, vol. 62, no. 2, pp. 127–136, 2003. View at Google Scholar
  11. R. W. Keane, A. R. Davis, and W. D. Dietrich, “Inflammatory and apoptotic signaling after spinal cord injury,” Journal of Neurotrauma, vol. 23, no. 3-4, pp. 335–344, 2006. View at Publisher · View at Google Scholar · View at PubMed
  12. H. M. Bramlett and W. D. Dietrich, “Pathophysiology of cerebral ischemia and brain trauma: similarities and differences,” Journal of Cerebral Blood Flow and Metabolism, vol. 24, no. 2, pp. 133–150, 2004. View at Google Scholar
  13. R. A. North, “Molecular physiology of P2X receptors,” Physiological Reviews, vol. 82, no. 4, pp. 1013–1067, 2002. View at Google Scholar
  14. G. Burnstock, “Introduction: P2 receptors,” Current Topics in Medicinal Chemistry, vol. 4, no. 8, pp. 793–803, 2004. View at Google Scholar
  15. B. S. Khakh and R. A. North, “P2X receptors as cell-surface ATP sensors in health and disease,” Nature, vol. 442, no. 7102, pp. 527–532, 2006. View at Publisher · View at Google Scholar · View at PubMed
  16. R. A. North and A. Surprenant, “Pharmacology of cloned P2X receptors,” Annual Review of Pharmacology and Toxicology, vol. 40, pp. 563–580, 2000. View at Publisher · View at Google Scholar · View at PubMed
  17. A. Surprenant, F. Rassendren, E. Kawashima, R. A. North, and G. Buell, “The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7),” Science, vol. 272, no. 5262, pp. 735–738, 1996. View at Publisher · View at Google Scholar
  18. T. M. Egan, D. S. K. Samways, and Z. Li, “Biophysics of P2X receptors,” Pflügers Archiv European Journal of Physiology, vol. 452, no. 5, pp. 501–512, 2006. View at Publisher · View at Google Scholar · View at PubMed
  19. G. Collo, S. Neidhart, E. Kawashima, M. Kosco-Vilbois, R. A. North, and G. Buell, “Tissue distribution of the P2X7 receptor,” Neuropharmacology, vol. 36, no. 9, pp. 1277–1283, 1997. View at Publisher · View at Google Scholar
  20. J. A. Sim, M. T. Young, H.-Y. Sung, R. A. North, and A. Surprenant, “Reanalysis of P2X7 receptor expression in rodent brain,” The Journal of Neuroscience, vol. 24, no. 28, pp. 6307–6314, 2004. View at Publisher · View at Google Scholar · View at PubMed
  21. C. M. Anderson and M. Nedergaard, “Emerging challenges of assigning P2X7 receptor function and immunoreactivity in neurons,” Trends in Neurosciences, vol. 29, no. 5, pp. 257–262, 2006. View at Publisher · View at Google Scholar · View at PubMed
  22. X.-F. Zhang, P. Han, C. R. Faltynek, M. F. Jarvis, and C.-C. Shieh, “Functional expression of P2X7 receptors in non-neuronal cells of rat dorsal root ganglia,” Brain Research, vol. 1052, no. 1, pp. 63–70, 2005. View at Publisher · View at Google Scholar · View at PubMed
  23. D. Ferrari, P. Chiozzi, S. Falzoni, S. Hanau, and F. Di Virgilio, “Purinergic modulation of interleukin-1β release from microglial cells stimulated with bacterial endotoxin,” Journal of Experimental Medicine, vol. 185, no. 3, pp. 579–582, 1997. View at Publisher · View at Google Scholar
  24. C. Virginio, A. MacKenzie, R. A. North, and A. Surprenant, “Kinetics of cell lysis, dye uptake and permeability changes in cells expressing the rat P2X7 receptor,” The Journal of Physiology, vol. 519, no. 2, pp. 335–346, 1999. View at Publisher · View at Google Scholar
  25. A. Filippini, R. E. Taffs, T. Agui, and M. V. Sitkovsky, “Ecto-ATPase activity in cytolytic T-lymphocytes. Protection from the cytolytic effects of extracellular ATP,” The Journal of Biological Chemistry, vol. 265, no. 1, pp. 334–340, 1990. View at Google Scholar
  26. A. Sikora, J. Liu, C. Brosnan, G. Buell, I. Chessel, and B. R. Bloom, “Cutting edge: purinergic signaling regulates radical-mediated bacterial killing mechanisms in macrophages through a P2X7-independent mechanism,” The Journal of Immunology, vol. 163, no. 2, pp. 558–561, 1999. View at Google Scholar
  27. D. Ferrari, P. Chiozzi, S. Falzoni et al., “ATP-mediated cytotoxicity in microglial cells,” Neuropharmacology, vol. 36, no. 9, pp. 1295–1301, 1997. View at Publisher · View at Google Scholar
  28. R. Beigi, E. Kobatake, M. Aizawa, and G. R. Dubyak, “Detection of local ATP release from activated platelets using cell surface-attached firefly luciferase,” American Journal of Physiology, vol. 276, no. 1, pp. C267–C278, 1999. View at Google Scholar
  29. G. R. Dubyak and C. el-Moatassim, “Signal transduction via P2-purinergic receptors for extracellular ATP and other nucleotides,” The American Journal of Physiology, vol. 265, no. 3, pp. C577–C606, 1993. View at Google Scholar
  30. E. R. Lazarowski, R. C. Boucher, and T. K. Harden, “Constitutive release of ATP and evidence for major contribution of ecto-nucleotide pyrophosphatase and nucleoside diphosphokinase to extracellular nucleotide concentrations,” The Journal of Biological Chemistry, vol. 275, no. 40, pp. 31061–31068, 2000. View at Publisher · View at Google Scholar · View at PubMed
  31. K. Nieber, D. Eschke, and A. Brand, “Brain hypoxia: effects of ATP and adenosine,” Progress in Brain Research, vol. 120, pp. 287–297, 1999. View at Publisher · View at Google Scholar
  32. B. D. Humphreys and G. R. Dubyak, “Modulation of P2X7 nucleotide receptor expression by pro- and anti-inflammatory stimuli in THP-1 monocytes,” Journal of Leukocyte Biology, vol. 64, no. 2, pp. 265–273, 1998. View at Google Scholar
  33. L. Narcisse, E. Scemes, Y. Zhao, S. C. Lee, and C. F. Brosnan, “The cytokine IL-1β transiently enhances P2X7 receptor expression and function in human astrocytes,” GLIA, vol. 49, no. 2, pp. 245–258, 2005. View at Publisher · View at Google Scholar · View at PubMed
  34. M. Solle, J. Labasi, D. G. Perregaux et al., “Altered cytokine production in mice lacking P2X7 receptors,” The Journal of Biological Chemistry, vol. 276, no. 1, pp. 125–132, 2001. View at Publisher · View at Google Scholar · View at PubMed
  35. J. M. Labasi, N. Petrushova, C. Donovan et al., “Absence of the P2X7 receptor alters leukocyte function and attenuates an inflammatory response,” The Journal of Immunology, vol. 168, no. 12, pp. 6436–6445, 2002. View at Google Scholar
  36. I. P. Chessell, J. P. Hatcher, C. Bountra et al., “Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain,” Pain, vol. 114, no. 3, pp. 386–396, 2005. View at Publisher · View at Google Scholar · View at PubMed
  37. L. K. Parvathenani, S. Tertyshnikova, C. R. Greco, S. B. Roberts, B. Robertson, and R. Posmantur, “P2X7 mediates superoxide production in primary microglia and is up-regulated in a transgenic mouse model of Alzheimer's disease,” The Journal of Biological Chemistry, vol. 278, no. 15, pp. 13309–13317, 2003. View at Publisher · View at Google Scholar · View at PubMed
  38. A. M. Basso, N. A. Bratcher, R. R. Harris, M. F. Jarvis, M. W. Decker, and L. E. Rueter, “Behavioral profile of P2X7 receptor knockout mice in animal models of depression and anxiety: relevance for neuropsychiatric disorders,” Behavioural Brain Research, vol. 198, no. 1, pp. 83–90, 2009. View at Publisher · View at Google Scholar · View at PubMed
  39. G. D. Eslick, B. V. Thampan, M. Nalos, A. S. McLean, and R. Sluyter, “Circulating interleukin-18 concentrations and a loss-of-function P2X7 polymorphism in heart failure,” International Journal of Cardiology. In press. View at Publisher · View at Google Scholar · View at PubMed
  40. B. D. Humphreys, J. Rice, S. B. Kertesy, and G. R. Dubyak, “Stress-activated protein kinase/JNK activation and apoptotic induction by the macrophage P2X7 nucleotide receptor,” The Journal of Biological Chemistry, vol. 275, no. 35, pp. 26792–26798, 2000. View at Publisher · View at Google Scholar · View at PubMed
  41. M. Aga, C. J. Johnson, A. P. Hart et al., “Modulation of monocyte signaling and pore formation in response to agonists of the nucleotide receptor P2X7,” Journal of Leukocyte Biology, vol. 72, no. 1, pp. 222–232, 2002. View at Google Scholar
  42. Y. D. Potucek, J. M. Crain, and J. J. Watters, “Purinergic receptors modulate MAP kinases and transcription factors that control microglial inflammatory gene expression,” Neurochemistry International, vol. 49, no. 2, pp. 204–214, 2006. View at Publisher · View at Google Scholar · View at PubMed
  43. A. Rao, C. Luo, and P. G. Hogan, “Transcription factors of the NFAT family: regulation and function,” Annual Review of Immunology, vol. 15, pp. 707–747, 1997. View at Publisher · View at Google Scholar · View at PubMed
  44. D. Ferrari, C. Stroh, and K. Schulze-Osthoff, “P2X7/P2Z purinoreceptor-mediated activation of transcription factor NFAT in microglial cells,” The Journal of Biological Chemistry, vol. 274, no. 19, pp. 13205–13210, 1999. View at Publisher · View at Google Scholar
  45. B. Mayr and M. Montminy, “Transcriptional regulation by the phosphorylation-dependent factor CREB,” Nature Reviews Molecular Cell Biology, vol. 2, no. 8, pp. 599–609, 2001. View at Publisher · View at Google Scholar · View at PubMed
  46. V. C. Foletta, D. H. Segal, and D. R. Cohen, “Transcriptional regulation in the immune system: all roads lead to AP-1,” Journal of Leukocyte Biology, vol. 63, no. 2, pp. 139–152, 1998. View at Google Scholar
  47. V. Budagian, E. Bulanova, L. Brovko et al., “Signaling through P2X7 receptor in human T cells involves p56lck, MAP kinases, and transcription factors AP-1 and NF-κB,” The Journal of Biological Chemistry, vol. 278, no. 3, pp. 1549–1560, 2003. View at Publisher · View at Google Scholar · View at PubMed
  48. J. J. Watters, J. A. Sommer, P. L. Fisette et al., “P2X7 nucleotide receptor: modulation of LPS-induced macrophage signaling and mediator production,” Drug Development Research, vol. 53, no. 2-3, pp. 91–104, 2001. View at Publisher · View at Google Scholar
  49. E. Adinolfi, M. Kim, M. T. Young, F. Di Virgilio, and A. Surprenant, “Tyrosine phosphorylation of HSP90 within the P2X7 receptor complex negatively regulates P2X7 receptors,” The Journal of Biological Chemistry, vol. 278, no. 39, pp. 37344–37351, 2003. View at Publisher · View at Google Scholar · View at PubMed
  50. M. Aga, J. J. Watters, Z. A. Pfeiffer, G. J. Wiepz, J. A. Sommer, and P. J. Bertics, “Evidence for nucleotide receptor modulation of cross talk between MAP kinase and NF-κB signaling pathways in murine RAW 264.7 macrophages,” American Journal of Physiology, vol. 286, no. 4, pp. C923–C930, 2004. View at Publisher · View at Google Scholar · View at PubMed
  51. Z. A. Pfeiffer, M. Aga, U. Prabhu, J. J. Watters, D. J. Hall, and P. J. Bertics, “The nucleotide receptor P2X7 mediates actin reorganization and membrane blebbing in RAW 264.7 macrophages via p38 MAP kinase and Rho,” Journal of Leukocyte Biology, vol. 75, no. 6, pp. 1173–1182, 2004. View at Publisher · View at Google Scholar · View at PubMed
  52. A. MacKenzie, H. L. Wilson, E. Kiss-Toth, S. K. Dower, R. A. North, and A. Surprenant, “Rapid secretion of interleukin-1β by microvesicle shedding,” Immunity, vol. 15, no. 5, pp. 825–835, 2001. View at Publisher · View at Google Scholar
  53. S. M. Allan and N. J. Rothwell, “Cytokines and acute neurodegeneration,” Nature Reviews Neuroscience, vol. 2, no. 10, pp. 734–744, 2001. View at Publisher · View at Google Scholar · View at PubMed
  54. R. Le Feuvre, D. Brough, and N. Rothwell, “Extracellular ATP and P2X7 receptors in neurodegeneration,” European Journal of Pharmacology, vol. 447, no. 2-3, pp. 261–269, 2002. View at Publisher · View at Google Scholar
  55. L. Bernardino, S. Balosso, T. Ravizza et al., “Inflammatory events in hippocampal slice cultures prime neuronal susceptibility to excitotoxic injury: a crucial role of P2X7 receptor-mediated IL-1β release,” Journal of Neurochemistry, vol. 106, no. 1, pp. 271–280, 2008. View at Publisher · View at Google Scholar · View at PubMed
  56. X. Wang, G. Arcuino, T. Takano et al., “P2X7 receptor inhibition improves recovery after spinal cord injury,” Nature Medicine, vol. 10, no. 8, pp. 821–827, 2004. View at Publisher · View at Google Scholar · View at PubMed
  57. S. D. Skaper, L. Facci, A. A. Culbert et al., “P2X7 receptors on microglial cells mediate injury to cortical neurons in vitro,” GLIA, vol. 54, no. 3, pp. 234–242, 2006. View at Publisher · View at Google Scholar · View at PubMed
  58. H. Franke, A. Günther, J. Grosche et al., “P2X7 receptor expression after ischemia in the cerebral cortex of rats,” Journal of Neuropathology and Experimental Neurology, vol. 63, no. 7, pp. 686–699, 2004. View at Google Scholar
  59. C. Volanté, S. Amadio, F. Cavaliere, N. D'Ambrosi, F. Vacca, and G. Bernardi, “Extracellular ATP and neurodegeneration,” Current Drug Targets-CNS & Neurological Disorders, vol. 2, no. 6, pp. 403–412, 2003. View at Publisher · View at Google Scholar
  60. S. Honda, Y. Sasaki, K. Ohsawa et al., “Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors,” The Journal of Neuroscience, vol. 21, no. 6, pp. 1975–1982, 2001. View at Google Scholar
  61. C. Verderio and M. Matteoli, “ATP mediates calcium signaling between astrocytes and microglial cells: modulation by IFN-γ,” The Journal of Immunology, vol. 166, no. 10, pp. 6383–6391, 2001. View at Google Scholar
  62. G. Burnstock and J. N. Wood, “Purinergic receptors: their role in nociception and primary afferent neurotransmission,” Current Opinion in Neurobiology, vol. 6, no. 4, pp. 526–532, 1996. View at Publisher · View at Google Scholar
  63. R. D. Fields and G. Burnstock, “Purinergic signalling in neuron-glia interactions,” Nature Reviews Neuroscience, vol. 7, no. 6, pp. 423–436, 2006. View at Publisher · View at Google Scholar · View at PubMed
  64. C. E. Jahr and T. M. Jessell, “ATP excites a subpopulation of rat dorsal horn neurones,” Nature, vol. 304, no. 5928, pp. 730–733, 1983. View at Publisher · View at Google Scholar
  65. E. L. Werry, G. J. Liu, and M. R. Bennett, “Glutamate-stimulated ATP release from spinal cord astrocytes is potentiated by substance P,” Journal of Neurochemistry, vol. 99, no. 3, pp. 924–936, 2006. View at Publisher · View at Google Scholar · View at PubMed
  66. V. Raghavendra and J. A. DeLeo, “The role of astrocytes and microglia in persistent pain,” Advances in Molecular and Cell Biology, vol. 31, pp. 951–966, 2003. View at Publisher · View at Google Scholar
  67. E. D. Milligan, S. F. Maier, and L. R. Watkins, “Review: neuronal-glial interactions in central sensitization,” Seminars in Pain Medicine, vol. 1, no. 3, pp. 171–183, 2003. View at Publisher · View at Google Scholar
  68. M. Costigan and C. J. Woolf, “Pain: molecular mechanisms,” The Journal of Pain, vol. 1, no. 3, part 2, pp. 35–44, 2000. View at Publisher · View at Google Scholar
  69. G. Dell'Antonio, A. Quattrini, E. Dal Cin, A. Fulgenzi, and M. E. Ferrero, “Antinociceptive effect of a new P2Z/P2X7 antagonist, oxidized ATP, in arthritic rats,” Neuroscience Letters, vol. 327, no. 2, pp. 87–90, 2002. View at Publisher · View at Google Scholar
  70. O. Touzani, H. Boutin, R. Lefeuvre et al., “Interleukin-1 influences ischemic brain damage in the mouse independently of the interleukin-1 type I receptor,” The Journal of Neuroscience, vol. 22, no. 1, pp. 38–43, 2002. View at Google Scholar
  71. B. Safieh-Garabedian, S. Poole, A. Allchorne, J. Winter, and C. J. Woolf, “Contribution of interleukin-1β to the inflammation-induced increase in nerve growth factor levels and inflammatory hyperalgesia,” British Journal of Pharmacology, vol. 115, no. 7, pp. 1265–1275, 1995. View at Google Scholar
  72. C. Sommer, S. Petrausch, T. Lindenlaub, and K. V. Toyka, “Neutralizing antibodies to interleukin 1-receptor reduce pain associated behavior in mice with experimental neuropathy,” Neuroscience Letters, vol. 270, no. 1, pp. 25–28, 1999. View at Publisher · View at Google Scholar
  73. G. H. Merriman, L. Ma, P. Shum et al., “Synthesis and SAR of novel 4,5-diarylimidazolines as potent P2X7 receptor antagonists,” Bioorganic and Medicinal Chemistry Letters, vol. 15, no. 2, pp. 435–438, 2005. View at Publisher · View at Google Scholar · View at PubMed
  74. D. W. Nelson, R. J. Gregg, M. E. Kort et al., “Structure-activity relationship studies on a series of novel, substituted 1-benzyl-5-phenyltetrazole P2X7 antagonists,” Journal of Medicinal Chemistry, vol. 49, no. 12, pp. 3659–3666, 2006. View at Publisher · View at Google Scholar · View at PubMed
  75. W. A. Carroll, D. M. Kalvin, A. Perez-Medrano et al., “Novel and potent 3-(2,3-dichlorophenyl)-4-(benzyl)-4H-1,2,4-triazole P2X7 antagonists,” Bioorganic & Medicinal Chemistry Letters, vol. 17, no. 14, pp. 4044–4048, 2007. View at Publisher · View at Google Scholar · View at PubMed
  76. M. Furber, L. Alcaraz, J. E. Bent et al., “Discovery of potent and selective adamantane-based small-molecule P2X7 receptor antagonists/interleukin-1β inhibitors,” Journal of Medicinal Chemistry, vol. 50, no. 24, pp. 5882–5885, 2007. View at Publisher · View at Google Scholar · View at PubMed
  77. D. W. Nelson, K. Sarris, D. M. Kalvin et al., “Structure-activity relationship studies on N-aryl carbohydrazide P2X7 antagonists,” Journal of Medicinal Chemistry, vol. 51, no. 10, pp. 3030–3034, 2008. View at Publisher · View at Google Scholar · View at PubMed
  78. P. Honore, D. Donnelly-Roberts, M. T. Namovic et al., “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,” Journal of Pharmacology and Experimental Therapeutics, vol. 319, no. 3, pp. 1376–1385, 2006. View at Publisher · View at Google Scholar · View at PubMed
  79. S. McGaraughty, K. L. Chu, M. T. Namovic et al., “P2X7-related modulation of pathological nociception in rats,” Neuroscience, vol. 146, no. 4, pp. 1817–1828, 2007. View at Publisher · View at Google Scholar · View at PubMed
  80. D. C. Broom, D. J. Matson, E. Bradshaw et al., “Characterization of N-(adamantan-1-ylmethyl)-5-[(3R-amino-pyrrolidin-1-yl) methyl]-2-chloro-benzamide, a P2X7 antagonist in animal models of pain and inflammation,” Journal of Pharmacology and Experimental Therapeutics, vol. 327, no. 3, pp. 620–633, 2008. View at Publisher · View at Google Scholar · View at PubMed
  81. R. S. Smith, “The macrophage theory of depression,” Medical Hypotheses, vol. 35, no. 4, pp. 298–306, 1991. View at Publisher · View at Google Scholar
  82. H. Anisman, Z. Merali, M. O. Poulter, and S. Hayley, “Cytokines as a precipitant of depressive illness: animal and human studies,” Current Pharmaceutical Design, vol. 11, no. 8, pp. 963–972, 2005. View at Publisher · View at Google Scholar
  83. Y. Pollak and R. Yirmiya, “Cytokine-induced changes in mood and behaviour: implications for ‘depression due to a general medical condition’, immunotherapy and antidepressive treatment,” International Journal of Neuropsychopharmacology, vol. 5, no. 4, pp. 389–399, 2002. View at Publisher · View at Google Scholar · View at PubMed
  84. S. Hayley, M. O. Poulter, Z. Merali, and H. Anisman, “The pathogenesis of clinical depression: stressor- and cytokine-induced alterations of neuroplasticity,” Neuroscience, vol. 135, no. 3, pp. 659–678, 2005. View at Publisher · View at Google Scholar · View at PubMed
  85. M. R. Kraus, A. Schäfer, H. Faller, H. Csef, and M. Scheurlen, “Paroxetine for the treatment of interferon-α-induced depression in chronic hepatitis C,” Alimentary Pharmacology and Therapeutics, vol. 16, no. 6, pp. 1091–1099, 2002. View at Publisher · View at Google Scholar
  86. J. Steiner, H. Bielau, R. Brisch et al., “Immunological aspects in the neurobiology of suicide: elevated microglial density in schizophrenia and depression is associated with suicide,” Journal of Psychiatric Research, vol. 42, no. 2, pp. 151–157, 2008. View at Publisher · View at Google Scholar · View at PubMed
  87. C. L. Raison, L. Capuron, and A. H. Miller, “Cytokines sing the blues: inflammation and the pathogenesis of depression,” Trends in Immunology, vol. 27, no. 1, pp. 24–31, 2006. View at Publisher · View at Google Scholar · View at PubMed
  88. C. Tuglu, S. H. Kara, O. Caliyurt, E. Vardar, and E. Abay, “Increased serum tumor necrosis factor-alpha levels and treatment response in major depressive disorder,” Psychopharmacology, vol. 170, no. 4, pp. 429–433, 2003. View at Publisher · View at Google Scholar · View at PubMed
  89. S. Alesci, P. E. Martinez, S. Kelkar et al., “Major depression is associated with significant diurnal elevations in plasma interleukin-6 levels, a shift of its circadian rhythm, and loss of physiological complexity in its secretion: clinical implications,” The Journal of Clinical Endocrinology & Metabolism, vol. 90, no. 5, pp. 2522–2530, 2005. View at Publisher · View at Google Scholar · View at PubMed
  90. B. B. Simen, C. H. Duman, A. A. Simen, and R. S. Duman, “TNFα signaling in depression and anxiety: behavioral consequences of individual receptor targeting,” Biological Psychiatry, vol. 59, no. 9, pp. 775–785, 2006. View at Publisher · View at Google Scholar · View at PubMed
  91. N. Barden, M. Harvey, B. Gagné et al., “Analysis of single nucleotide polymorphisms in genes in the chromosome 12Q24.31 region points to P2RX7 as a susceptibility gene to bipolar affective disorder,” American Journal of Medical Genetics Part B, vol. 141, no. 4, pp. 374–382, 2006. View at Publisher · View at Google Scholar · View at PubMed
  92. S. Lucae, D. Salyakina, N. Barden et al., “P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder,” Human Molecular Genetics, vol. 15, no. 16, pp. 2438–2445, 2006. View at Publisher · View at Google Scholar · View at PubMed
  93. K. Hejjas, A. Szekely, E. Domotor et al., “Association between depression and the Gln460Arg polymorphism of P2RX7 gene: a dimensional approach,” American Journal of Medical Genetics Part B, vol. 150, no. 2, pp. 295–299, 2009. View at Publisher · View at Google Scholar · View at PubMed
  94. J. S. Wiley, L.-P. Dao-Ung, C. Li et al., “An Ile-568 to Asn polymorphism prevents normal trafficking and function of the human P2X7 receptor,” The Journal of Biological Chemistry, vol. 278, no. 19, pp. 17108–17113, 2003. View at Publisher · View at Google Scholar · View at PubMed
  95. L. C. Denlinger, G. Angelini, K. Schell et al., “Detection of human P2X7 nucleotide receptor polymorphisms by a novel monocyte pore assay predictive of alterations in lipopolysaccharide-induced cytokine production,” The Journal of Immunology, vol. 174, no. 7, pp. 4424–4431, 2005. View at Google Scholar
  96. A. M. Basso, N. A. Bratcher, R. R. Harris, M. F. Jarvis, M. W. Decker, and L. E. Rueter, “Behavioral profile of P2X7 receptor knockout mice in animal models of depression and anxiety: relevance for neuropsychiatric disorders,” Behavioural Brain Research, vol. 198, no. 1, pp. 83–90, 2009. View at Publisher · View at Google Scholar · View at PubMed
  97. M. Maes, “The immunoregulatory effects of antidepressants,” Human Psychopharmacology, vol. 16, no. 1, pp. 95–103, 2001. View at Publisher · View at Google Scholar · View at PubMed
  98. Z. Xia, J. W. DePierre, and L. Nässberger, “Tricyclic antidepressants inhibit IL-6, IL-1β and TNF-α release in human blood monocytes and IL-2 and interferon-γ in T cells,” Immunopharmacology, vol. 34, no. 1, pp. 27–37, 1996. View at Publisher · View at Google Scholar
  99. D. Brustolim, R. Ribeiro-dos-Santos, R. E. Kast, E. L. Altschuler, and M. B. P. Soares, “A new chapter opens in anti-inflammatory treatments:the antidepressant bupropion lowers production of tumor necrosis factor-alpha and interferon-gamma in mice,” International Immunopharmacology, vol. 6, no. 6, pp. 903–907, 2006. View at Publisher · View at Google Scholar · View at PubMed
  100. R. Yirmiya, Y. Pollak, O. Barak et al., “Effects of antidepressant drugs on the behavioral and physiological responses to lipopolysaccharide (LPS) in rodents,” Neuropsychopharmacology, vol. 24, no. 5, pp. 531–544, 2001. View at Publisher · View at Google Scholar · View at PubMed
  101. S. Lanquillon, J.-C. Krieg, U. Bening-Abu-Shach, and H. Vedder, “Cytokine production and treatment response in major depressive disorder,” Neuropsychopharmacology, vol. 22, no. 4, pp. 370–379, 2000. View at Publisher · View at Google Scholar
  102. V. Ralevic, “Purines as neurotransmitters and neuromodulators in blood vessels,” Current Vascular Pharmacology, vol. 7, no. 1, pp. 3–14, 2009. View at Publisher · View at Google Scholar
  103. R. A. Olsson and J. D. Pearson, “Cardiovascular purinoceptors,” Physiological Reviews, vol. 70, no. 3, pp. 761–845, 1990. View at Google Scholar
  104. C. J. Lewis and R. J. Evans, “P2X receptor immunoreactivity in different arteries from the femoral, pulmonary, cerebral, coronary and renal circulations,” Journal of Vascular Research, vol. 38, no. 4, pp. 332–340, 2001. View at Publisher · View at Google Scholar
  105. J. K. Phillips, A. J. McLean, and C. E. Hill, “Receptors involved in nerve-mediated vasoconstriction in small arteries of the rat hepatic mesentery,” British Journal of Pharmacology, vol. 124, no. 7, pp. 1403–1412, 1998. View at Publisher · View at Google Scholar · View at PubMed
  106. P. Valdecantos, R. Briones, P. Moya, A. Germain, and J. P. Huidobro-Toro, “Pharmacological identification of P2X1, P2X4 and P2X7 nucleotide receptors in the smooth muscles of human umbilical cord and chorionic blood vessels,” Placenta, vol. 24, no. 1, pp. 17–26, 2003. View at Publisher · View at Google Scholar
  107. F. D. Reilly and P. T. Russell, “Neurohistochemical evidence supporting an absence of adrenergic and cholinergic innervation in the human placenta and umbilical cord,” Anatomical Record, vol. 188, no. 3, pp. 277–286, 1977. View at Publisher · View at Google Scholar · View at PubMed
  108. G. Froldi, K. Varani, A. Chinellato, E. Ragazzi, L. Caparrotta, and P. A. Borea, “P2X-purinoceptors in the heart: actions of ATP and UTP,” Life Sciences, vol. 60, no. 17, pp. 1419–1430, 1997. View at Publisher · View at Google Scholar
  109. A. Chinellato, E. Ragazzi, L. Pandolfo, G. Froldi, L. Caparrotta, and G. Fassina, “Pharmacological characterization of ATP receptors mediating vasodilation on isolated rabbit aorta,” General Pharmacology, vol. 23, no. 5, pp. 861–865, 1992. View at Publisher · View at Google Scholar
  110. A. Chinellato, E. Ragazzi, L. Pandolfo, G. Froldi, L. Caparrotta, and G. Fassina, “Pharmacological characterization of a new purinergic receptor site in rabbit aorta,” General Pharmacology, vol. 23, no. 6, pp. 1067–1071, 1992. View at Publisher · View at Google Scholar
  111. A. Chinellato, E. Ragazzi, L. Pandolfo, G. Froldi, L. Caparrotta, and G. Fassina, “Purine- and nucleotide-mediated relaxation of rabbit thoracic aorta: common and different sites of action,” Journal of Pharmacy and Pharmacology, vol. 46, no. 5, pp. 337–341, 1994. View at Google Scholar
  112. W. A. Thomas, J. M. Reiner, R. A. Florentin, K. T. Lee, and W. M. Lee, “Population dynamics of arterial smooth muscle cells: V. Cell proliferation and cell death during initial 3 months in atherosclerotic lesions induced in swine by hypercholesterolemic diet and intimal trauma,” Experimental and Molecular Pathology, vol. 24, no. 3, pp. 360–374, 1976. View at Publisher · View at Google Scholar
  113. Z. Mallat and A. Tedgui, “Apoptosis in the vasculature: mechanisms and functional importance,” British Journal of Pharmacology, vol. 130, no. 5, pp. 947–962, 2000. View at Publisher · View at Google Scholar · View at PubMed
  114. G. Burnstock, “Release of vasoactive substances from endothelial cells by shear stress and purinergic mechanosensory transduction,” Journal of Anatomy, vol. 194, no. 3, pp. 335–342, 1999. View at Publisher · View at Google Scholar
  115. D. Kaiser, M.-A. Freyberg, and P. Friedl, “Lack of hemodynamic forces triggers apoptosis in vascular endothelial cells,” Biochemical and Biophysical Research Communications, vol. 231, no. 3, pp. 586–590, 1997. View at Publisher · View at Google Scholar · View at PubMed
  116. G. H. Gibbons, “Autocrine-paracrine factors and vascular remodeling in hypertension,” Current Opinion in Nephrology and Hypertension, vol. 2, no. 2, pp. 291–298, 1993. View at Publisher · View at Google Scholar
  117. M. Baroni, C. Pizzirani, M. Pinotti et al., “Stimulation of P2 (P2X7) receptors in human dendritic cells induces the release of tissue factor-bearing microparticles,” The FASEB Journal, vol. 21, no. 8, pp. 1926–1933, 2007. View at Publisher · View at Google Scholar · View at PubMed
  118. C.-W. Chiao, R. C. Tostes, and R. C. Webb, “P2X7 receptor activation amplifies lipopolysaccharide-induced vascular hyporeactivity via interleukin-1β release,” Journal of Pharmacology and Experimental Therapeutics, vol. 326, no. 3, pp. 864–870, 2008. View at Publisher · View at Google Scholar · View at PubMed
  119. J. Palomino-Doza, T. J. Rahman, P. J. Avery et al., “Ambulatory blood pressure is associated with polymorphic variation in P2X receptor genes,” Hypertension, vol. 52, no. 5, pp. 980–985, 2008. View at Publisher · View at Google Scholar · View at PubMed
  120. A. Pelleg and G. Burnstock, “Physiological importance of ATP released from nerve terminals and its degradation to adenosine in humans,” Circulation, vol. 82, no. 6, pp. 2269–2272, 1990. View at Google Scholar
  121. C. Cario-Toumaniantz, G. Loirand, A. Ladoux, and P. Pacaud, “P2X7 receptor activation-induced contraction and lysis in human saphenous vein smooth muscle,” Circulation Research, vol. 83, no. 2, pp. 196–203, 1998. View at Google Scholar
  122. C. Michiels, T. Arnould, and J. Remacle, “Hypoxia-induced activation of endothelial cells as a possible cause of venous diseases: hypothesis,” Angiology, vol. 44, no. 8, pp. 639–646, 1993. View at Publisher · View at Google Scholar
  123. S. C. Robson, E. Kaczmarek, J. B. Siegel et al., “Loss of ATP diphosphohydrolase activity with endothelial cell activation,” Journal of Experimental Medicine, vol. 185, no. 1, pp. 153–163, 1997. View at Publisher · View at Google Scholar
  124. J. A. Brock and T. C. Cunnane, “Effects of Ca2+ concentration and Ca2+ channel blockers on noradrenaline release and purinergic neuroeffector transmission in rat tail artery,” British Journal of Pharmacology, vol. 126, no. 1, pp. 11–18, 1999. View at Publisher · View at Google Scholar · View at PubMed
  125. D. Ramme, J. T. Regenold, K. Starke, R. Busse, and P. Illes, “Identification of the neuroeffector transmitter in jejunal branches of the rabbit mesenteric artery,” Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 336, no. 3, pp. 267–273, 1987. View at Publisher · View at Google Scholar
  126. N. M. Rummery, J. A. Brock, P. Pakdeechote, V. Ralevic, and W. R. Dunn, “ATP is the predominant sympathetic neurotransmitter in rat mesenteric arteries at high pressure,” The Journal of Physiology, vol. 582, no. 2, pp. 745–754, 2007. View at Publisher · View at Google Scholar · View at PubMed
  127. J. N. Wilcox and N. A. Scott, “Potential role of the adventitia in arteritis and atherosclerosis,” International Journal of Cardiology, vol. 54, pp. S21–S35, 1996. View at Google Scholar
  128. C. D. Buckley, D. Pilling, J. M. Lord, A. N. Akbar, D. Scheel-Toellner, and M. Salmon, “Fibroblasts regulate the switch from acute resolving to chronic persistent inflammation,” Trends in Immunology, vol. 22, no. 4, pp. 199–204, 2001. View at Publisher · View at Google Scholar
  129. D. Strehlow and J. H. Korn, “Biology of the scleroderma fibroblast,” Current Opinion in Rheumatology, vol. 10, no. 6, pp. 572–578, 1998. View at Publisher · View at Google Scholar
  130. E. Chiquette and R. Chilton, “Cardiovascular disease: much more aggressive in patients with type 2 diabetes,” Current Atherosclerosis Reports, vol. 4, no. 2, pp. 134–142, 2002. View at Publisher · View at Google Scholar
  131. M. A. M. Loots, S. B. Kenter, F. L. Au et al., “Fibroblasts derived from chronic diabetic ulcers differ in their response to stimulation with EGF, IGF-I, bFGF and PDGF-AB compared to controls,” European Journal of Cell Biology, vol. 81, no. 3, pp. 153–160, 2002. View at Publisher · View at Google Scholar
  132. F. Di Virgilio and A. Solini, “P2 receptors: new potential players in atherosclerosis,” The British Journal of Pharmacology, vol. 135, no. 4, pp. 831–842, 2002. View at Publisher · View at Google Scholar · View at PubMed
  133. A. Solini, P. Chiozzi, A. Morelli et al., “Enhanced P2X7 activity in human fibroblasts from diabetic patients: a possible pathogenetic mechanism for vascular damage in diabetes,” Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 24, no. 7, pp. 1240–1245, 2004. View at Publisher · View at Google Scholar · View at PubMed
  134. J. L. Andersen, L. M. Rasmussen, and J. P. Ledet, “Diabetic macroangiopathy and atherosclerosis,” Diabetes, vol. 45, pp. S91–S94, 1996. View at Google Scholar
  135. T. Sugiyama, H. Oku, A. Komori, and T. Ikeda, “Effect of P2X7 receptor activation on the retinal blood velocity of diabetic rabbits,” Archives of Ophthalmology, vol. 124, no. 8, pp. 1143–1149, 2006. View at Publisher · View at Google Scholar · View at PubMed
  136. M. Monif, C. A. Reid, K. L. Powell, M. L. Smart, and D. A. Williams, “The P2X7 receptor drives microglial activation and proliferation: a trophic role for P2X7R pore,” The Journal of Neuroscience, vol. 29, no. 12, pp. 3781–3791, 2009. View at Publisher · View at Google Scholar · View at PubMed
  137. B. Sperlágh, E. S. Vizi, K. Wirkner, and P. Illes, “P2X7 receptors in the nervous system,” Progress in Neurobiology, vol. 78, no. 6, pp. 327–346, 2006. View at Publisher · View at Google Scholar · View at PubMed
  138. A. Witting, L. Chen, E. Cudaback et al., “Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 16, pp. 6362–6367, 2006. View at Publisher · View at Google Scholar · View at PubMed
  139. D. Ferrari, C. Pizzirani, E. Adinolfi et al., “The P2X7 receptor: a key player in IL-1 processing and release,” The Journal of Immunology, vol. 176, no. 7, pp. 3877–3883, 2006. View at Google Scholar
  140. V. Ralevic and G. Burnstock, “Involvement of purinergic signaling in cardiovascular diseases,” Drug News and Perspectives, vol. 16, no. 3, pp. 133–140, 2003. View at Publisher · View at Google Scholar