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P2rx7  -  purinergic receptor P2X, ligand-gated ion...

Rattus norvegicus

Synonyms: ATP receptor, P2X purinoceptor 7, P2X7, P2Z receptor, Purinergic receptor
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Disease relevance of P2rx7


Psychiatry related information on P2rx7


High impact information on P2rx7

  • P2X7 receptor inhibition improves recovery after spinal cord injury [6].
  • Thus, the P2X7 (or P2Z) receptor is a bifunctional molecule that could function in both fast synaptic transmission and the ATP-mediated lysis of antigen-presenting cells [7].
  • The P2Z receptor is responsible for adenosine triphosphate (ATP)-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules [7].
  • When either the capsaicin receptor, TRPV1, the menthol receptor, TRPM8, or the ionotropic purinergic receptor P2X(2) was introduced into hippocampal neurons, the cells responded to pulsed applications of agonist with characteristic sequences of depolarization, spiking, and repolarization [8].
  • Infusion of ATP by way of the portal vein directly activated hepatic JNK signaling, while infusion of a P2 purinergic receptor antagonist prior to partial hepatectomy inhibited JNK activation [9].

Chemical compound and disease context of P2rx7

  • Both Brilliant Blue G and oxidized ATP inhibited the release of [3H]GABA caused by ATP application; the Brilliant Blue G-sensitive, P2X7 receptor-mediated fraction, was much larger after ischemia than after normoxia [10].
  • When compared with normoxia, ischemia appears to markedly increase P2X7 receptor-mediated GABA release, which may limit the severity of the ischemic damage [10].
  • Short-term hyperthyroidism modulates the fat-cell adenylate cyclase system at the receptor level (beta-receptor number increased, R-site purinergic-receptor number decreased) and the catalytic subunit of adenylate cyclase [11].
  • Reactive blue 2 inhibition of cyclic AMP-dependent differentiation of rat C6 glioma cells by purinergic receptor-independent inactivation of phosphatidylinositol 3-kinase [12].
  • The stimulation of prostaglandin E2 production and Ca2+ influx by ATP is inhibited by pertussis toxin treatment, indicating that ATP mediates its effect by binding to a G-protein-coupled purinergic receptor [13].

Biological context of P2rx7

  • Although the pharmacology and channel properties of the P2X7 receptors have been studied intensively, signal transduction pathways are relatively unknown [14].
  • Most important, we found that treatment of the microglia in neuron-microglia cocultures with the P2X7 agonist 2'-3'-O-(benzoyl-benzoyl) ATP led to significant reductions in glutamate-induced neuronal cell death, and that either TNF-alpha converting enzyme inhibitor or anti-TNF readily suppressed the protective effect implied by this result [1].
  • In conclusion, the present data demonstrate a postischemic, time-dependent upregulation of the P2X7 receptor-subtype on neurons and glial cells and suggest a role for this receptor in the pathophysiology of cerebral ischemia in vivo [2].
  • We first examined rats, but staining patterns were inconsistent among antibodies; we therefore studied mice for which there are two P2X7 knock-out mice constructs available, one expressing the LacZ transgene [15].
  • Together, these findings indicate that AA mediates a complex regulation of [Ca(2+)](i) dynamics also through P2X7-mediated Ca(2+) entry, suggesting that variations in AA production may be relevant to the control of both the temporal and spatial kinetics of [Ca(2+)](i) signaling in astroglial cells [16].

Anatomical context of P2rx7

  • EGFP-P2X7 receptors localized to the plasma membrane, clusters within the membrane and intracellularly [14].
  • P2X7 nucleotide receptors modulate a spectrum of cellular events in various cells including epithelia, such as exocrine pancreas [14].
  • In cell suspensions prepared from rat pancreas we show that P2X7 receptors also activate ERK1 and ERK2, indicating that these signalling pathways are also turned on in native epithelium [14].
  • P2X7 and GABRP identified in this study could be used as potential AEC I and AEC II markers for studying lung epithelial cell biology and monitoring lung injury [17].
  • Immunostaining on cultured cells and rat lung tissue indicated that GABRP and P2X7 proteins were specifically expressed in AEC II and AEC I, respectively [17].

Associations of P2rx7 with chemical compounds


Physical interactions of P2rx7

  • In pure ductal suspensions, ATP activated a metabotropic P2Y1 purinergic receptor coupled to phospholipase C and opened a non-specific cation channel coupled to a P2X7 receptor [21].

Regulatory relationships of P2rx7

  • P2X7 receptors activate protein kinase D and p42/p44 mitogen-activated protein kinase (MAPK) downstream of protein kinase C [22].
  • P2X7 receptor immunoreactivity was also expressed in epithelial cells and colocalised with caspase 9 (an apoptotic marker), suggesting an association with apoptosis and epithelial turnover [23].

Other interactions of P2rx7

  • Exogenously added NGF then augmented hypoglycemic neuronal death by about 60%, increasing the percentage of Höechst-positive nuclei (from approximately 62 to 95%), reducing lactate dehydrogenase (LDH) release (from about 50 to 14%) and significantly overstimulating the hypoglycemia-induced expression of P2X7 and P2Y4 [24].
  • Bz-ATP also increased MCP-1 expression in cultured astrocytes, and again P2X7 antagonists prevented this increase [25].
  • Somatic and axonal effects of ATP via P2X2 but not P2X7 receptors in rat thoracolumbar sympathetic neurones [26].
  • Double immunofluorescence visualized with confooal laser scanning microscopy indicated the localization of the P2X7 receptor after ischemia on microglial cells (after 1 and 4 days), on tubulin betaIII-labeled neurons (after 4 and 7 days), and on glial fibrillary acidic protein (GFAP)-positive astrocytes (after 4 days) [2].
  • Almost all the microglial cells that were positive for the marker ED1, expressed P2X1 and P2X4 receptors, whereas only about 30% of the cells with ED1-immunoreactivity were found to express the P2X7 receptor [27].

Analytical, diagnostic and therapeutic context of P2rx7

  • Astrocytes in primary cell culture and acutely isolated from the hippocampus were immunopositive for P2X7 receptors [25].
  • Western blot analysis of the cortical tissue around the area of necrosis indicated an increase in the P2X7 receptor protein [2].
  • By using microfluorometry, we investigated the action of extracellular AA in the modulation of the purinoceptor P2X7-mediated elevation of [Ca(2+)](i) in cultured neocortical type-1 astrocytes and P2X7-, P2X2-transfected human embryonic kidney (HEK) 293 cells [16].
  • Reverse transcription-polymerase chain reaction (RT-PCR) was used to characterize the expression of P2X receptor subunits (P2X1-P2X7) in different inner ear tissues [28].
  • Procedures to characterize and study P2Z/P2X7 purinoceptor: flow cytometry as a promising practical, reliable tool [29].


  1. Production and release of neuroprotective tumor necrosis factor by P2X7 receptor-activated microglia. Suzuki, T., Hide, I., Ido, K., Kohsaka, S., Inoue, K., Nakata, Y. J. Neurosci. (2004) [Pubmed]
  2. P2X7 receptor expression after ischemia in the cerebral cortex of rats. Franke, H., Günther, A., Grosche, J., Schmidt, R., Rossner, S., Reinhardt, R., Faber-Zuschratter, H., Schneider, D., Illes, P. J. Neuropathol. Exp. Neurol. (2004) [Pubmed]
  3. ATP-induced non-neuronal cell permeabilization in the rat inner retina. Innocenti, B., Pfeiffer, S., Zrenner, E., Kohler, K., Guenther, E. J. Neurosci. (2004) [Pubmed]
  4. Identification of P2X7 (P2Z) receptor in N18TG-2 cells and NG108-15 cells. Kaiho, H., Matsuoka, I., Kimura, J., Nakanishi, H. J. Neurochem. (1998) [Pubmed]
  5. P2X7 mediates superoxide production in primary microglia and is up-regulated in a transgenic mouse model of Alzheimer's disease. Parvathenani, L.K., Tertyshnikova, S., Greco, C.R., Roberts, S.B., Robertson, B., Posmantur, R. J. Biol. Chem. (2003) [Pubmed]
  6. P2X7 receptor inhibition improves recovery after spinal cord injury. Wang, X., Arcuino, G., Takano, T., Lin, J., Peng, W.G., Wan, P., Li, P., Xu, Q., Liu, Q.S., Goldman, S.A., Nedergaard, M. Nat. Med. (2004) [Pubmed]
  7. The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Surprenant, A., Rassendren, F., Kawashima, E., North, R.A., Buell, G. Science (1996) [Pubmed]
  8. Photochemical gating of heterologous ion channels: remote control over genetically designated populations of neurons. Zemelman, B.V., Nesnas, N., Lee, G.A., Miesenbock, G. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  9. Extracellular ATP activates c-jun N-terminal kinase signaling and cell cycle progression in hepatocytes. Thevananther, S., Sun, H., Li, D., Arjunan, V., Awad, S.S., Wyllie, S., Zimmerman, T.L., Goss, J.A., Karpen, S.J. Hepatology (2004) [Pubmed]
  10. Supersensitivity of P2X receptors in cerebrocortical cell cultures after in vitro ischemia. Wirkner, K., Köfalvi, A., Fischer, W., Günther, A., Franke, H., Gröger-Arndt, H., Nörenberg, W., Madarász, E., Vizi, E.S., Schneider, D., Sperlágh, B., Illes, P. J. Neurochem. (2005) [Pubmed]
  11. Short-term hyperthyroidism modulates adenosine receptors and catalytic activity of adenylate cyclase in adipocytes. Rapiejko, P.J., Malbon, C.C. Biochem. J. (1987) [Pubmed]
  12. Reactive blue 2 inhibition of cyclic AMP-dependent differentiation of rat C6 glioma cells by purinergic receptor-independent inactivation of phosphatidylinositol 3-kinase. Claes, P., Van Kolen, K., Roymans, D., Blero, D., Vissenberg, K., Erneux, C., Verbelen, J.P., Esmans, E.L., Slegers, H. Biochem. Pharmacol. (2004) [Pubmed]
  13. Regulation of arachidonic acid release and prostaglandin E2 production in thymic epithelial cells by ATPgammaS and transforming growth factor-alpha. Liu, P., Lalor, D., Bowser, S.S., Hayden, J.H., Wen, M., Hayashi, J. Cell. Immunol. (1998) [Pubmed]
  14. P2X7 receptor activates extracellular signal-regulated kinases ERK1 and ERK2 independently of Ca2+ influx. Amstrup, J., Novak, I. Biochem. J. (2003) [Pubmed]
  15. Reanalysis of P2X7 receptor expression in rodent brain. Sim, J.A., Young, M.T., Sung, H.Y., North, R.A., Surprenant, A. J. Neurosci. (2004) [Pubmed]
  16. Potentiation of native and recombinant P2X7-mediated calcium signaling by arachidonic acid in cultured cortical astrocytes and human embryonic kidney 293 cells. Alloisio, S., Aiello, R., Ferroni, S., Nobile, M. Mol. Pharmacol. (2006) [Pubmed]
  17. Identification of two novel markers for alveolar epithelial type I and II cells. Chen, Z., Jin, N., Narasaraju, T., Chen, J., McFarland, L.R., Scott, M., Liu, L. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  18. Involvement of chloride in apoptotic cell death induced by activation of ATP-sensitive P2X7 purinoceptor. Tsukimoto, M., Harada, H., Ikari, A., Takagi, K. J. Biol. Chem. (2005) [Pubmed]
  19. Bi-functional effects of ATP/P2 receptor activation on tumor necrosis factor-alpha release in lipopolysaccharide-stimulated astrocytes. Kucher, B.M., Neary, J.T. J. Neurochem. (2005) [Pubmed]
  20. Expression of P2X7 receptor immunoreactivity in distinct subsets of synaptic terminals in the ventral horn of rat lumbar spinal cord. Deng, Z., Fyffe, R.E. Brain Res. (2004) [Pubmed]
  21. Purines, a new class of agonists in salivary glands? Dehaye, J.P., Moran, A., Marino, A. Arch. Oral Biol. (1999) [Pubmed]
  22. P2X7 receptors activate protein kinase D and p42/p44 mitogen-activated protein kinase (MAPK) downstream of protein kinase C. Bradford, M.D., Soltoff, S.P. Biochem. J. (2002) [Pubmed]
  23. Immunolocalisation of P2X and P2Y nucleotide receptors in the rat nasal mucosa. Gayle, S., Burnstock, G. Cell Tissue Res. (2005) [Pubmed]
  24. Extracellular ATP and nerve growth factor intensify hypoglycemia-induced cell death in primary neurons: role of P2 and NGFRp75 receptors. Cavaliere, F., Sancesario, G., Bernardi, G., Volonté, C. J. Neurochem. (2002) [Pubmed]
  25. P2X7-like receptor activation in astrocytes increases chemokine monocyte chemoattractant protein-1 expression via mitogen-activated protein kinase. Panenka, W., Jijon, H., Herx, L.M., Armstrong, J.N., Feighan, D., Wei, T., Yong, V.W., Ransohoff, R.M., MacVicar, B.A. J. Neurosci. (2001) [Pubmed]
  26. Somatic and axonal effects of ATP via P2X2 but not P2X7 receptors in rat thoracolumbar sympathetic neurones. Allgaier, C., Reinhardt, R., Schädlich, H., Rubini, P., Bauer, S., Reichenbach, A., Illes, P. J. Neurochem. (2004) [Pubmed]
  27. Expression of P2X receptors on rat microglial cells during early development. Xiang, Z., Burnstock, G. Glia (2005) [Pubmed]
  28. Gene expression of P2X-receptors in the developing inner ear of the rat. Brändle, U., Zenner, H.P., Ruppersberg, J.P. Neurosci. Lett. (1999) [Pubmed]
  29. Procedures to characterize and study P2Z/P2X7 purinoceptor: flow cytometry as a promising practical, reliable tool. Nihei, O.K., Savino, W., Alves, L.A. Mem. Inst. Oswaldo Cruz (2000) [Pubmed]
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