The Cytolytic P 2Z Receptor for Extracellular ATP Identified as a P 2X Receptor (P2X 7 )
Abstract
The P 2Z receptor is responsible for adenosine triphosphate (ATP)-dependent lysis of macrophages through the formation of membrane pores permeable to large molecules. Other ATP-gated channels, the P 2X receptors, are permeable only to small cations. Here, an ATP receptor, the P2X 7 receptor, was cloned from rat brain and exhibited both these properties. This protein is homologous to other P 2X receptors but has a unique carboxyl-terminal domain that was required for the lytic actions of ATP. Thus, the P2X 7 (or P 2Z ) receptor is a bifunctional molecule that could function in both fast synaptic transmission and the ATP-mediated lysis of antigen-presenting cells.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Activation of P2X7 needs high concentrations of ATP (mM level), much higher than concentrations for other purinergic receptors (μM level).
“Activation of P2X7 needs a high concentrations of ATP (mM level), which is much higher than the concentrations for other purinergic receptors (μM level).376”
From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [376]
Cited by
Sorted by citations
The NLRP3 inflammasome: molecular activation and regulation to therapeutics
Swanson, K. V., Deng, M., & Ting, J. P.-Y. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0165-0 · Cited by 4,884 · see citing works
Molecular Physiology of P2X Receptors
North, R. A. (2002) · Physiological Reviews · doi:10.1152/physrev.00015.2002 · Cited by 2,919 · see citing works
Self-citationRole of neuroinflammation in neurodegeneration development
Zhang, W., Xiao, D., Mao, Q., & Xia, H. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01486-5 · Cited by 1,668 · see citing works
The P2X7 Receptor in Infection and Inflammation
Di Virgilio, F., Dal Ben, D., Sarti, A. C., Giuliani, A. L., & Falzoni, S. (2017) · Immunity · doi:10.1016/j.immuni.2017.06.020 · Cited by 1,267 · see citing works
Bours, M. J. L., Swennen, E. L. R., Di Virgilio, F., Cronstein, B. N., & Dagnelie, P. C. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.04.013 · Cited by 1,030 · see citing works
The P2X7 Receptor: A Key Player in IL-1 Processing and Release
Ferrari, D., Pizzirani, C., Adinolfi, E., Lemoli, R. M., Curti, A., Idzko, M., Panther, E., & Di Virgilio, F. (2006) · The Journal of Immunology · doi:10.4049/jimmunol.176.7.3877 · Cited by 1,025 · see citing works
The ectonucleotidases <scp>CD</scp> 39 and <scp>CD</scp> 73: Novel checkpoint inhibitor targets
Allard, B., Longhi, M. S., Robson, S. C., & Stagg, J. (2017) · Immunological Reviews · doi:10.1111/imr.12528 · Cited by 927 · see citing works
Initiation and perpetuation of <scp>NLRP</scp> 3 inflammasome activation and assembly
Elliott, E. I., & Sutterwala, F. S. (2015) · Immunological Reviews · doi:10.1111/imr.12286 · Cited by 821 · see citing works
Yiangou, Y., Facer, P., Durrenberger, P., Chessell, I. P., Naylor, A., Bountra, C., Banati, R. R., & Anand, P. (2006) · BMC Neurology · doi:10.1186/1471-2377-6-12 · Cited by 509 · see citing works
Liaisons dangereuses: P2X7 and the inflammasome
Di Virgilio, F. (2007) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2007.07.002 · Cited by 493 · see citing works
P2X <sub>7</sub> Receptor-Mediated Release of Excitatory Amino Acids from Astrocytes
Duan, S., Anderson, C. M., Keung, E. C., Chen, Y., Chen, Y., & Swanson, R. A. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-04-01320.2003 · Cited by 489 · see citing works
Neutrophil P2X7 receptors mediate NLRP3 inflammasome-dependent IL-1β secretion in response to ATP
Karmakar, M., Katsnelson, M. A., Dubyak, G. R., & Pearlman, E. (2016) · Nature Communications · doi:10.1038/ncomms10555 · Cited by 450 · see citing works
The P2X7 Receptor in Inflammatory Diseases: Angel or Demon?
Savio, L. E. B., de Andrade Mello, P., da Silva, C. G., & Coutinho-Silva, R. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.00052 · Cited by 437 · see citing works
The P2X7 receptor: A main player in inflammation
Adinolfi, E., Giuliani, A. L., De Marchi, E., Pegoraro, A., Orioli, E., & Di Virgilio, F. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2017.12.021 · Cited by 385 · see citing works
Immune regulation by microbiome metabolites
Kim, C. H. (2018) · Immunology · doi:10.1111/imm.12930 · Cited by 375 · see citing works
Monif, M., Reid, C. A., Powell, K. L., Smart, M. L., & Williams, D. A. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5512-08.2009 · Cited by 374 · see citing works
Cytokines and the central nervous system
Szelényi, J. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00428-2 · Cited by 358 · see citing works
Franchi, L., Kanneganti, T.-D., Dubyak, G. R., & Núñez, G. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m610762200 · Cited by 356 · see citing works
Deuchars, S. A., Atkinson, L., Brooke, R. E., Musa, H., Milligan, C. J., Batten, T. F. C., Buckley, N. J., Parson, S. H., & Deuchars, J. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-18-07143.2001 · Cited by 287 · see citing works
Di Virgilio, F., Schmalzing, G., & Markwardt, F. (2018) · Trends in Cell Biology · doi:10.1016/j.tcb.2018.01.005 · Cited by 279 · see citing works
Sperlágh, B., Köfalvi, A., Deuchars, J., Atkinson, L., J. Milligan, C., Buckley, N. J., & Vizi, E. S. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00920.x · Cited by 264 · see citing works
Lucae, S., Salyakina, D., Barden, N., Harvey, M., Gagné, B., Labbé, M., Binder, E. B., Uhr, M., Paez-Pereda, M., Sillaber, I., et al. (2006) · Human Molecular Genetics · doi:10.1093/hmg/ddl166 · Cited by 261 · see citing works
Ritter, M., Gross, O., Kays, S., Ruland, J., Nimmerjahn, F., Saijo, S., Tschopp, J., Layland, L. E., & Prazeres da Costa, C. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1010337107 · Cited by 243 · see citing works
Sluyter, R. (2017) · Advances in Experimental Medicine and Biology · doi:10.1007/5584_2017_59 · Cited by 235 · see citing works
Nucleoside reverse transcriptase inhibitors possess intrinsic anti-inflammatory activity
Fowler, B. J., Gelfand, B. D., Kim, Y., Kerur, N., Tarallo, V., Hirano, Y., Amarnath, S., Fowler, D. H., Radwan, M., Young, M. T., et al. (2014) · Science · doi:10.1126/science.1261754 · Cited by 225 · see citing works
P2X7 receptors mediate ischemic damage to oligodendrocytes
Domercq, M., Perez‐Samartin, A., Aparicio, D., Alberdi, E., Pampliega, O., & Matute, C. (2010) · Glia · doi:10.1002/glia.20958 · Cited by 221 · see citing works
The microglial ATP‐gated ion channel P2X7 as a CNS drug target
Bhattacharya, A., & Biber, K. (2016) · Glia · doi:10.1002/glia.23001 · Cited by 221 · see citing works
P2X7 Interactions and Signaling – Making Head or Tail of It
Kopp, R., Krautloher, A., Ramírez-Fernández, A., & Nicke, A. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00183 · Cited by 217 · see citing works
P2X Receptors in Health and Disease
Burnstock, G., & Kennedy, C. (2011) · Advances in Pharmacology · doi:10.1016/b978-0-12-385526-8.00011-4 · Cited by 213 · see citing works
Shieh, C., Heinrich, A., Serchov, T., van Calker, D., & Biber, K. (2014) · Glia · doi:10.1002/glia.22628 · Cited by 179 · see citing works
Neuronal P2X7 Receptors Revisited: Do They Really Exist?
Illes, P., Khan, T. M., & Rubini, P. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.3103-16.2017 · Cited by 179 · see citing works
Smart, M. L., Gu, B., Panchal, R. G., Wiley, J., Cromer, B., Williams, D. A., & Petrou, S. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211094200 · Cited by 170 · see citing works
Connexins: Key Mediators of Endocrine Function
Bosco, D., Haefliger, J.-A., & Meda, P. (2011) · Physiological Reviews · doi:10.1152/physrev.00027.2010 · Cited by 169 · see citing works
The P2X7 Receptor-Interleukin-1 Liaison
Giuliani, A. L., Sarti, A. C., Falzoni, S., & Di Virgilio, F. (2017) · Frontiers in Pharmacology · doi:10.3389/fphar.2017.00123 · Cited by 166 · see citing works
The P2X7 Receptor: Central Hub of Brain Diseases
Andrejew, R., Oliveira-Giacomelli, Á., Ribeiro, D. E., Glaser, T., Arnaud-Sampaio, V. F., Lameu, C., & Ulrich, H. (2020) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2020.00124 · Cited by 162 · see citing works
Significance of P2X7 Receptor Variants to Human Health and Disease
Sluyter, R., & Stokes, L. (2011) · Recent Patents on DNA & Gene Sequences · doi:10.2174/187221511794839219 · Cited by 147 · see citing works
Cellular localization of P2X7 receptor mRNA in the rat brain
Yu, Y., Ugawa, S., Ueda, T., Ishida, Y., Inoue, K., Kyaw Nyunt, A., Umemura, A., Mase, M., Yamada, K., & Shimada, S. (2008) · Brain Research · doi:10.1016/j.brainres.2007.11.064 · Cited by 132 · see citing works
P2X7 Receptor Signaling in Stress and Depression
Ribeiro, D. E., Roncalho, A. L., Glaser, T., Ulrich, H., Wegener, G., & Joca, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20112778 · Cited by 129 · see citing works
Properties of the pore‐forming P2X<sub>7</sub> purinoceptor in mouse NTW8 microglial cells
Chessell, I. P., Michel, A. D., & Humphrey, P. P. A. (1997) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701278 · Cited by 126 · see citing works
Effects of antagonists at the human recombinant P2X<sub>7</sub> receptor
Chessell, I. P., Michel, A. D., & Humphrey, P. P. A. (1998) · British Journal of Pharmacology · doi:10.1038/sj.bjp.0701958 · Cited by 115 · see citing works
Csölle, C., Andó, R. D., Kittel, Á., Gölöncsér, F., Baranyi, M., Soproni, K., Zelena, D., Haller, J., Németh, T., Mócsai, A., et al. (2013) · International Journal of Neuropsychopharmacology · doi:10.1017/s1461145711001933 · Cited by 108 · see citing works
“The homo-oligomeric P2rx7 (Surprenant et al. 1996) has distinct structural, functional and pharmacological features within the P2X receptor family (Jarvis & Khakh, 2009 ; Sperlagh et al. 2006) : (1) its intracellular carboxyl-terminal domain is longer than those of other P2X receptor subunits ; (2)…”
BackgroundLack of ATP-evoked GABA and glutamate release in the hippocampus of P2X7 receptor-/- mice
Papp, L., Vizi, E. S., & Sperlágh, B. (2004) · Neuroreport · doi:10.1097/00001756-200410250-00017 · Cited by 102 · see citing works
P2X7 Receptor: A Potential Therapeutic Target for Depression?
Deussing, J. M., & Arzt, E. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.07.005 · Cited by 97 · see citing works
Wirkner, K., Köfalvi, A., Fischer, W., Günther, A., Franke, H., Gröger‐Arndt, H., Nörenberg, W., Madarász, E., Vizi, E. S., Schneider, D., et al. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03465.x · Cited by 89 · see citing works
Masuch, A., Shieh, C., van Rooijen, N., van Calker, D., & Biber, K. (2016) · Glia · doi:10.1002/glia.22904 · Cited by 81 · see citing works
The role of p2x7 receptor in infectious inflammatory diseases and the influence of ectonucleotidases
Coutinho-Silva, R., Morandini, A., & Savio, L. B. (2014) · Biomedical Journal · doi:10.4103/2319-4170.127803 · Cited by 81 · see citing works
Metzger, M. W., Walser, S. M., Dedic, N., Aprile-Garcia, F., Jakubcakova, V., Adamczyk, M., Webb, K. J., Uhr, M., Refojo, D., Schmidt, M. V., et al. (2017) · The Journal of Neuroscience · doi:10.1523/jneurosci.3487-16.2017 · Cited by 59 · see citing works
León, D., Sánchez-Nogueiro, J., Marín-García, P., & Miras-Portugal, M. T. (2008) · Neurochemistry International · doi:10.1016/j.neuint.2007.12.004 · Cited by 53 · see citing works
The role of P2X7 receptors in a rodent PCP-induced schizophrenia model
Koványi, B., Csölle, C., Calovi, S., Hanuska, A., Kató, E., Köles, L., Bhattacharya, A., Haller, J., & Sperlágh, B. (2016) · Scientific Reports · doi:10.1038/srep36680 · Cited by 52 · see citing works
Lahne, M., & Gale, J. E. (2010) · Purinergic Signalling · doi:10.1007/s11302-010-9193-8 · Cited by 36 · see citing works
Duan, L., Hu, G.-H., Li, Y.-J., Zhang, C.-L., & Jiang, M. (2018) · Molecular Immunology · doi:10.1016/j.molimm.2018.07.027 · Cited by 23 · see citing works
- Authors
- Surprenant, A., Rassendren, F., Kawashima, E., North, R. A., & Buell, G.
- Affiliations
- Glaxo Institute for Molecular Biology, Plan-les-Ouates, 1228 Geneva, Switzerland.
- Corresponding author
- Surprenant, A.
- ORCID
- North, R. A.
- Venue
- Science
- Published
- 1996-05-03
- Volume
- 272
- Issue
- 5262
- Pages
- 735-738
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2066784771
- Cited by
- 1,739
- References
- 0
- Citations by year
- 2026: 19 · 2025: 40 · 2024: 49 · 2023: 61 · 2022: 63 · 2021: 67 · 2020: 61 · 2019: 34 · 2018: 52 · 2017: 52 · 2016: 46 · 2015: 54 · 2014: 52 · 2013: 52 · 2012: 70
- FWCI
- 35.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Neuroscience › Sensory Systems › Ion Channels and Receptors
- Keywords
- P2X7 receptor, P2Z receptor, extracellular ATP, ATP-gated ion channels, macrophage lysis, membrane pores, receptor cloning, C-terminal domain, synaptic transmission, antigen-presenting cells, purinergic signaling
- MeSH terms
- Adenosine Triphosphate, Amino Acid Sequence, Animals, Base Sequence, Cations, Divalent, Cell Line, Cloning, Molecular, Electric Conductivity, Humans, Ion Channels, Molecular Sequence Data, Transfection, Cell Death, Receptors, Purinergic P2, DNA, Complementary, Patch-Clamp Techniques, Mice, Rats, Receptors, Purinergic P2X7
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
