Affinage

P2RX7

P2X purinoceptor 7 · UniProt Q99572

Length
595 aa
Mass
68.6 kDa
Annotated
2026-06-10
100 papers in source corpus 18 papers cited in narrative 19 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

P2RX7 (P2X7R) is an ATP-gated cation channel whose activation couples extracellular nucleotide sensing to membrane permeabilization and a broad program of inflammatory, metabolic, and proliferative signaling (PMID:25690658, PMID:26542019). Its cytoplasmic C-terminus serves as a signaling hub: an SH3 death domain engages Src kinase to drive Pannexin-1 large-conductance currents and dye-permeable membrane permeabilization (PMID:18596211), and upon ATP/BzATP stimulation the receptor is recruited to subplasmalemmal sites where localized Ca2+ rises promote its direct association with the NLRP3 inflammasome scaffold (PMID:25690658). Paxillin bridges P2X7R and NLRP3 into a ternary complex and enables USP13-mediated NLRP3 deubiquitination, a step required for ATP-induced inflammasome activation in macrophages, dendritic cells, and human monocytes (PMID:33243234). Through macropore formation the receptor drives unconventional secretion of transglutaminase-2 and vesicular shedding of CD14, the latter dampening LPS responsiveness and limiting bacterial burden in sepsis (PMID:26542019, PMID:33135636). P2X7R also localizes to mitochondria and is required for normal respiration, mitochondrial Ca2+ loading, and cardiac/physical fitness in vivo (PMID:35330818). In the tumor context it promotes tumor growth via NFATc1-dependent VEGF secretion and neoangiogenesis (PMID:22505653), yet in tumor-infiltrating CD8+ T cells it imposes mitochondrial-ROS/p38/p21-dependent senescence that restrains anti-tumor immunity (PMID:32699136). Receptor abundance is set epigenetically by Tet1/Tet2-dependent demethylation of the P2rX7 promoter, which controls exosome release and Runx2 signaling in mesenchymal stem cells (PMID:29858571), and post-transcriptionally by miR-211-5p (PMID:38191407). P2X7R further mediates paracrine UV-induced melanogenesis (PMID:30926287), macrophage multinucleated giant cell formation (PMID:10982408), and modulates seizure, autophagy, and radiation-response phenotypes across neural and tumor tissues (PMID:29749377, PMID:38191407, PMID:26358881).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 2000 Medium

    Established that P2X7R is not merely a channel but a driver of macrophage fusion, linking receptor activity to multinucleated giant cell formation and a cell-death effector.

    Evidence Monoclonal antibody blockade, P2X7-high/low cell selection, caspase-3 activity assay, and immunolocalization at cell contacts

    PMID:10982408

    Open questions at the time
    • Molecular fusion machinery downstream of P2X7R not identified
    • Direct caspase-3 substrate at contact sites unknown
  2. 2008 Medium

    Defined how the P2X7R C-terminus transduces signal beyond ion flux, showing its SH3 death domain recruits Src to activate Pannexin-1 and membrane permeabilization.

    Evidence Whole-cell patch-clamp, Panx1 siRNA, competing TAT-P2X7 C-terminal peptides, and pharmacological inhibition in a dye-uptake assay

    PMID:18596211

    Open questions at the time
    • Direct structural basis of SH3-Src binding not resolved
    • Whether Src acts directly on Panx1 not established
  3. 2012 High

    Showed P2X7R expression is sufficient to promote tumor growth, connecting receptor activity to NFATc1-driven VEGF secretion and neoangiogenesis.

    Evidence HEK293 xenografts with in vivo P2X7 silencing, oxidized-ATP and anti-VEGF (bevacizumab) intervention, immunohistochemistry

    PMID:22505653

    Open questions at the time
    • Link from P2X7R activation to NFATc1 activation not biochemically mapped
    • Endogenous tumor relevance vs. HEK overexpression
  4. 2015 High

    Identified the direct physical interaction between P2X7R and the NLRP3 scaffold, providing a spatial mechanism (subplasmalemmal Ca2+) for inflammasome assembly.

    Evidence Reciprocal Co-IP, confocal co-localization, calcium imaging, and P2X7R-/- primary cells with NLRP3 mRNA quantification

    PMID:25690658

    Open questions at the time
    • Interaction interface residues not mapped
    • Mechanism of Ca2+-driven recruitment unresolved
  5. 2015 High

    Demonstrated that P2X7R macropore formation, not Ca2+ or depolarization alone, drives unconventional TG2 secretion, dissecting pore activity from other receptor outputs.

    Evidence Heterologous HEK293 reconstitution, pharmacological dissection separating secretion from vesicle shedding, gain-of-function disease-mutant analysis

    PMID:26542019

    Open questions at the time
    • Molecular identity of the secretory route downstream of pore formation unknown
    • How TG2 accesses the pore not defined
  6. 2017 Medium

    Tested whether P2X4 and P2X7 form functional heteromers, finding physical association by FRET but no electrophysiologically distinct heteromeric channel.

    Evidence FRET between tagged subunits in Xenopus oocytes and two-electrode voltage clamp with subtype-selective pharmacology

    PMID:29213241

    Open questions at the time
    • Physiological significance of P2X4-P2X7 association unclear
    • Heteromer behavior in native cells untested
  7. 2018 High

    Revealed epigenetic control of P2rX7 abundance, placing the receptor downstream of Tet1/Tet2 demethylation in mesenchymal stem cell and bone homeostasis.

    Evidence Tet1/Tet2 DKO mice, promoter methylation analysis, exosome/miRNA profiling, and P2rX7 overexpression rescue of osteoporotic phenotype

    PMID:29858571

    Open questions at the time
    • How P2X7R activity controls exosome release mechanistically unclear
    • Direct miR-297/Runx2 link to receptor pore vs. signaling untested
  8. 2018 High

    Connected P2X7R to innate immune tuning by showing it sheds membrane CD14 in vesicles to attenuate LPS responses and limit bacterial load in sepsis.

    Evidence EV isolation, flow cytometry of membrane CD14, LPS stimulation, and P2X7-/- mouse sepsis model with bacterial load measurement

    PMID:33135636

    Open questions at the time
    • Mechanism coupling pore formation to CD14 vesicle loading not defined
    • Whether shedding is direct or via downstream proteases unknown
  9. 2018 Medium

    Linked P2X7R loss to dysregulated astroglial autophagy, defining a MAPK1/2-SP1-HSPB1 signaling axis after status epilepticus.

    Evidence P2rx7-/- mice in kainic acid model with phosphorylation analysis of SP1 and MAPK1/2 and autophagy pathway Western blots

    PMID:29749377

    Open questions at the time
    • Direct receptor-to-MAPK1/2 coupling not established
    • Single-lab in vivo correlative pathway data
  10. 2019 High

    Showed P2X7R mediates a paracrine keratinocyte-melanocyte signaling loop driving UV-induced melanogenesis via Ca2+/PKC/CREB and MITF.

    Evidence CRISPR/Cas9 P2X7 knockout melanocytes co-cultured with UV-irradiated keratinocytes, pharmacological blockade, MITF and melanin assays

    PMID:30926287

    Open questions at the time
    • Direct CREB target genes downstream not mapped
    • Relevance to human pigmentation in vivo untested
  11. 2020 High

    Defined paxillin as the molecular bridge linking P2X7R to NLRP3, with USP13-mediated deubiquitination as a required activation step.

    Evidence Co-IP of P2X7R-Paxillin-NLRP3 ternary complex, deubiquitination assay identifying USP13, and functional validation in mouse and human primary cells

    PMID:33243234

    Open questions at the time
    • How ATP triggers paxillin phosphorylation upstream unclear
    • Stoichiometry/order of ternary complex assembly unknown
  12. 2020 High

    Uncovered an immunosuppressive cell-intrinsic role: P2X7R drives senescence in tumor-infiltrating CD8+ T cells, identifying a target to enhance anti-tumor immunity.

    Evidence P2rx7-/- adoptive T cell transfer, mitochondrial ROS measurement, p38 MAPK inhibition, p21 upregulation, and in vivo tumor growth

    PMID:32699136

    Open questions at the time
    • How receptor signaling generates mitochondrial ROS not resolved
    • Whether senescence is reversible by transient blockade untested
  13. 2021 High

    Established a non-canonical mitochondrial localization for P2X7R essential for respiration, mitochondrial Ca2+, and organismal cardiac and physical fitness.

    Evidence Subcellular fractionation/confocal localization, Seahorse respirometry, mitochondrial Ca2+ measurement, and cardiac ultrasound plus fitness testing in P2rx7-/- mice

    PMID:35330818

    Open questions at the time
    • How P2X7R traffics to and functions within mitochondria unknown
    • Whether mitochondrial pool is channel-active not established
  14. 2022 Medium

    Showed P2X7R isoform balance shapes tumor radiation response, with irradiation switching from P2X7A to a growth-promoting P2X7B variant in glioblastoma.

    Evidence Isoform-specific RT-PCR/Western blot before and after irradiation with P2X7 blockade and viability assays

    PMID:35075119

    Open questions at the time
    • Mechanism of the trophic P2X7B signal not defined
    • Low-resolution dissection of isoform-specific function
  15. 2022 Medium

    Demonstrated pore-activity-dependent P2X7R function is required for glioma radiosensitivity in vitro and in vivo, framing the receptor as a radiotherapy modifier.

    Evidence P2X7R siRNA silencing, ethidium bromide pore uptake, annexin V apoptosis, and in vivo GL261 radiotherapy model

    PMID:26358881

    Open questions at the time
    • How pore activity links to radiation-induced death pathway unclear
    • Single-lab in vivo data
  16. 2022 Medium

    Showed P2X7R activation drives radiation-induced hyposalivation through PGE2 release, identifying a tissue-protection rationale for antagonism.

    Evidence P2X7R-/- mice, gamma-irradiation, salivary flow measurement, PGE2 assay from primary parotid cells, and A438079 antagonism

    PMID:30892913

    Open questions at the time
    • Coupling of receptor activation to PGE2 synthesis not mapped
    • Cell type responsible within gland unresolved
  17. 2024 Medium

    Placed P2RX7 within a miR-211-5p-controlled circuit that drives neuronal ferroptosis via GPX4/HO-1 and MAPK/ERK in epilepsy.

    Evidence Patient blood samples, PTZ and KA mouse models, miR-211-5p overexpression, P2RX7 silencing, GPX4/HO-1/ERK Western blots, and seizure scoring

    PMID:38191407

    Open questions at the time
    • Direct miR-211-5p binding to P2RX7 transcript needs confirmation
    • How receptor activity modulates ERK/GPX4 mechanistically unclear
  18. 2015 Medium

    Characterized species-specific pharmacological inhibitors of human P2X7R acting outside the known F95 site, with functional suppression of IL-1beta secretion.

    Evidence Recombinant human P2X7 in HEK-293, dye uptake, patch clamp, F95L mutagenesis, species comparison, and primary monocyte IL-1beta assay

    PMID:26341077

    Open questions at the time
    • Actual binding site of paroxetine/trifluoperazine not identified
    • Whether inhibition is allosteric or competitive unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single receptor coordinates its distinct outputs (channel, macropore, mitochondrial, scaffolding) at the structural and trafficking level, and whether these are spatially segregated receptor pools or sequential conformational states.
  • No structural model connecting pore dilation to scaffolding functions
  • Mechanism of mitochondrial targeting unknown
  • Determinants of context-specific signaling output undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0005215 transporter activity 2 GO:0060089 molecular transducer activity 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005886 plasma membrane 3 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9612973 Autophagy 1
Partners
NLRP3P2RX4PANX1PXNSRCUSP13
Complex memberships
P2X4-P2X7 heterotrimerP2X7R-Paxillin-NLRP3 ternary complex

Evidence

Reading pass · 19 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2008 P2X7 receptor C-terminal SH3 death domain interacts with Src tyrosine kinase, and this interaction mediates downstream Pannexin-1 (Panx1) activation. TAT-peptides spanning the P2X7R C-terminus competed with Src binding, reducing Panx1-dependent large-conductance currents and membrane permeabilization to dye. Src tyrosine phosphorylation following BzATP stimulation was blocked by KN-62, TAT-P2X7 peptide, and Src inhibitor PP2. Whole-cell patch-clamp electrophysiology, siRNA knockdown of Panx1, competition assay with membrane-permeant TAT-P2X7 peptides, pharmacological inhibition (KN-62, PP2, carbenoxolone, mefloquine), dye uptake permeabilization assay American journal of physiology. Cell physiology Medium 18596211
2015 P2X7 receptor directly interacts with NLRP3 inflammasome scaffold protein at discrete subplasmalemmal sites. ATP or BzATP stimulation caused localized cytoplasmic Ca2+ increases that drove P2X7R recruitment and a 4-fold increase in P2X7R/NLRP3 co-immunoprecipitation within 1–2 min. P2X7R down-modulation also caused 2–8-fold up-regulation of NLRP3 mRNA in microglial cells and primary macrophages from P2X7R-/- mice. Coimmunoprecipitation, confocal microscopy, RT-PCR, Western blot, calcium imaging, P2X7R-/- primary cells FASEB journal : official publication of the Federation of American Societies for Experimental Biology High 25690658
2020 Paxillin acts as a molecular bridge between P2X7 receptor and NLRP3 inflammasome. Extracellular ATP induces paxillin phosphorylation and promotes formation of a P2X7R-Paxillin-NLRP3 ternary complex at the plasma membrane. Paxillin facilitates NLRP3 deubiquitination via USP13, and paxillin is required for ATP-induced NLRP3 inflammasome activation in mouse BMDMs, BMDCs, and human PBMCs/THP-1 macrophages. Co-immunoprecipitation, confocal microscopy showing membrane translocation, genetic knockdown/knockout, deubiquitination assay, USP13 identification, human primary cell functional assays BMC biology High 33243234
2015 P2X7 receptor activation regulates rapid unconventional secretion of transglutaminase-2 (TG2). Extracellular ATP promotes TG2 secretion from macrophages via P2X7R; introduction of functional P2X7R into HEK293 cells is sufficient to confer TG2 export. TG2 release requires receptor membrane pore formation (not Ca2+ signaling alone or membrane depolarization), does not involve pannexin channels, and is pharmacologically separable from microvesicle shedding. A gain-of-function P2X7R mutation associated with autoimmune disease caused enhanced TG2 externalization correlating with increased pore activity. Pharmacological antagonism, heterologous expression in HEK293 cells, gain-of-function mutation analysis, separation of vesicle shedding from secretion by pharmacological agents, pore formation assay Journal of cell science High 26542019
2017 P2X4 and P2X7 receptor subunits can physically associate to form heterotrimeric channels, detected by FRET between fluorophore-labeled subunits in Xenopus oocytes. However, electrophysiological analysis of ATP-induced whole-cell currents, concentration-response curves, and effects of subtype-specific drugs (ivermectin, PSB-15417, oATP, A438079) were consistent with homomeric P2X4 and P2X7 channels coexisting, with no electrophysiologically distinct heteromeric phenotype. FRET between fluorophore-tagged subunits expressed in Xenopus oocytes, two-electrode voltage clamp electrophysiology, pharmacological dissection with subtype-selective agents Frontiers in pharmacology Medium 29213241
2021 P2X7 receptor localizes to mitochondria in fibroblasts, microglial cells, and heart tissue. Loss of P2X7R decreases basal respiratory rate, ATP-coupled respiration, maximal uncoupled respiration, resting mitochondrial potential, and mitochondrial matrix Ca2+ levels. P2X7R-null mice have larger hearts with smaller mitochondria, reduced stroke volume, ejection fraction, fractional shortening, and cardiac output, and severely reduced physical fitness. Subcellular fractionation and confocal localization to mitochondria, mitochondrial respirometry (Seahorse), mitochondrial Ca2+ measurement, cardiac ultrasound in P2rx7-/- mice, treadmill fitness testing Function (Oxford, England) High 35330818
2000 P2X7 receptor participates in multinucleated giant cell (MGC) formation. Blockade with a specific monoclonal antibody prevents macrophage fusion in vitro. P2X7-high expressing phagocytes fuse only with other P2X7-high cells. During MGC formation, caspase-3 is activated (a P2X7-stimulated enzyme), and P2X7R is preferentially localized at cell-to-cell contact sites. Monoclonal antibody blockade, cell selection for high/low P2X7 expression, caspase-3 activity assay, immunolocalization at cell contacts, ATP-degrading enzyme controls (apyrase/hexokinase) Molecular biology of the cell Medium 10982408
2012 P2X7 receptor expression promotes tumor growth in vivo. HEK293 cells expressing P2X7 showed increased tumorigenicity, proliferation, reduced apoptosis, elevated NFATc1 activation, enhanced vascular network, and elevated VEGF secretion compared to controls. Tumor growth and neoangiogenesis were blocked by intratumoral oxidized-ATP (P2X7 inhibitor), VEGF-blocking antibody bevacizumab, or P2X7 silencing in vivo. In vivo xenograft tumor model, intratumoral inhibitor injection, P2X7 silencing (siRNA in vivo), anti-VEGF antibody treatment, immunohistochemistry, VEGF measurement Cancer research High 22505653
2018 Tet1 and Tet2 methylcytosine dioxygenases maintain mesenchymal stem cell (MSC) homeostasis via demethylation of the P2rX7 promoter. Tet1/Tet2 double knockout reduces P2rX7 expression, decreasing exosome release and causing intracellular accumulation of miR-297a-5p, miR-297b-5p, and miR-297c-5p, which inhibit Runx2 signaling and impair BMMSC function. Overexpression of P2rX7 in Tet1/2 double KO mice rescues the impaired BMMSCs and osteoporotic phenotype. Genetic knockout (Tet1/Tet2 DKO mice), promoter methylation analysis, exosome quantification, miRNA profiling, Runx2 signaling assay, P2rX7 overexpression rescue experiment Nature communications High 29858571
2018 P2X7 receptor activation induces release of CD14 (a GPI-anchored LPS co-receptor) in extracellular vesicles from macrophages, resulting in net reduction of membrane CD14 and functionally attenuating LPS-induced (but not monophosphoryl lipid A-induced) pro-inflammatory cytokine production. In a murine sepsis model, P2X7 activity maintained elevated circulating CD14 levels; reduced P2X7 activity correlated with higher bacterial load, exacerbated organ damage, and premature death. Extracellular vesicle isolation, flow cytometry for CD14 membrane levels, LPS stimulation assay, P2X7-/- mice in a sepsis model, bacterial load measurement eLife High 33135636
2020 P2X7 stimulation of tumor-infiltrating effector CD8+ T cells induces cellular senescence via mitochondrial reactive oxygen species generation and p38 MAPK-dependent upregulation of Cdkn1a (p21Waf1/Cip1), impairing cell cycling. Adoptive transfer of P2rx7-/- tumor-specific CD8+ T cells significantly reduced tumor growth and extended survival compared to wild-type T cells in mice. Genetic KO (P2rx7-/-) adoptive T cell transfer, cell cycle analysis, mitochondrial ROS measurement, p38 MAPK inhibition, p21 upregulation assay, in vivo tumor growth measurement Cancer research High 32699136
2018 P2X7 receptor regulates astroglial autophagy (clasmatodendrosis) after status epilepticus through a MAPK1/2-SP1-HSPB1 signaling axis. Loss of P2rx7 leads to prolonged HSPB1 induction due to impaired MAPK1/2-mediated SP1 phosphorylation; upregulated HSPB1 then triggers ER stress and PRKAA1(AMPK1)/ULK1- and AKT1/GSK3B/SH3GLB1-mediated autophagic pathways independently of mTOR. P2rx7-/- mice, kainic acid-induced status epilepticus model, Western blot for pathway components, phosphorylation analysis of SP1 and MAPK1/2 Cell death & disease Medium 29749377
2019 ATP-P2X7 receptor axis promotes UV-induced melanogenesis. Extracellular ATP released from UVB-irradiated keratinocytes activates P2X7R on melanocytes to promote melanin production via intracellular Ca2+ and PKC/CREB signaling. CRISPR/Cas9 P2X7 knockout melanocytes (MNT1) failed to upregulate MITF when co-cultured with UV-irradiated keratinocytes, confirming P2X7R is required for this paracrine signaling. P2X7R pharmacological blockade, CRISPR/Cas9 knockout of P2X7 in melanocytes, co-culture with UV-irradiated keratinocytes, MITF expression assay, melanin measurement, Ca2+ signaling and PKC/CREB pathway analysis The Journal of investigative dermatology High 30926287
2022 Irradiation of glioblastoma (GBM) cells causes a dramatic isoform switch: P2X7A splice variant is down-regulated and P2X7B is up-regulated. P2X7B activation by extracellular ATP after irradiation generates a trophic/growth-promoting stimulus, as P2X7 blockers during post-irradiation recovery potentiated irradiation-dependent cytotoxicity. Isoform-specific RT-PCR/Western blot before and after irradiation, P2X7 pharmacological blockade post-irradiation, cell viability assays Cell death & disease Medium 35075119
2022 P2X7 receptor deletion in mice suppresses gamma-radiation-induced hyposalivation. Irradiated P2X7R-/- mice maintained normal stimulated salivary flow rates, whereas wild-type irradiated mice showed significant decreases. P2X7R activation elevated PGE2 release from parotid cells following gamma-radiation, and pharmacological P2X7R antagonism (A438079) preserved salivary flow rates in wild-type mice. P2X7R-/- mouse model, gamma-irradiation, stimulated salivary flow rate measurement, PGE2 release assay from primary parotid cells, pharmacological antagonism (A438079), apoptosis assay American journal of physiology. Regulatory, integrative and comparative physiology Medium 30892913
2024 microRNA-211-5p targets P2RX7 mRNA; downregulation of miR-211-5p in epilepsy causes P2RX7 upregulation. P2RX7 regulates GPX4/HO-1 by alleviating lipid peroxidation through suppression of MAPK/ERK signaling, contributing to neuronal ferroptosis. Genetic silencing of P2RX7 or induction of miR-211-5p significantly reduced seizure score and duration in murine models. Bioinformatics, epilepsy patient blood samples, mouse epilepsy models (PTZ and KA), miR-211-5p overexpression, P2RX7 genetic silencing, GPX4/HO-1/ERK pathway Western blot, seizure behavioral scoring Journal of neuroinflammation Medium 38191407
2022 P2X7 receptor expression is required for glioma radiosensitivity. P2X7R silencing blocked gamma-radiation (2 Gy)-induced cytotoxicity in glioma cells in a time-dependent pore-activity-dependent manner (measured by ethidium bromide uptake). In vivo, P2X7R-silenced GL261-bearing mice failed to respond to radiotherapy (8 Gy), while wild-type P2X7R-expressing mice showed significant tumor volume reduction. ATP acted synergistically with radiotherapy to increase annexin V incorporation. P2X7R siRNA silencing, pharmacological antagonism, ethidium bromide pore uptake assay, annexin V apoptosis assay, in vivo GL261 tumor model with radiotherapy, tumor volume measurement The international journal of biochemistry & cell biology Medium 26358881
2015 Paroxetine inhibits human P2X7 receptor responses in a concentration-dependent manner (IC50 ~24 µM), reducing ATP-induced dye uptake and inward currents. Trifluoperazine also suppresses human P2X7 responses (IC50 ~6.4 µM). Neither drug inhibited rodent P2X7, and mutation of residue F95L did not alter the inhibitory effect of either drug, indicating they do not bind at this known site. Both drugs suppressed P2X7-induced IL-1β secretion from LPS-primed human CD14+ monocytes. Recombinant human P2X7 in HEK-293 cells, dye uptake assay, whole-cell patch clamp, site-directed mutagenesis (F95L), primary human monocyte IL-1β secretion assay, species comparison (human vs. rodent P2X7) Purinergic signalling Medium 26341077
2022 P2X7 receptor activation by P2RX7 stimulation in glioblastoma cells promotes pore formation as measured by ethidium bromide uptake, and this activity is essential for radiation-induced cytotoxicity. Both P2X7A (full-length) and P2X7B (truncated C-terminus) isoforms are expressed in GBM, with distinct contributions to cell survival versus death responses. Isoform-specific expression analysis, ethidium bromide pore uptake assay, pharmacological blockade, irradiation experiments, cell viability Cell death & disease Low 35075119

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2017 The P2X7 Receptor in Infection and Inflammation. Immunity 1026 28723547
2007 Liaisons dangereuses: P2X(7) and the inflammasome. Trends in pharmacological sciences 414 17692395
2018 The P2X7 Receptor in Inflammatory Diseases: Angel or Demon? Frontiers in pharmacology 352 29467654
2014 The P2X7 receptor channel: recent developments and the use of P2X7 antagonists in models of disease. Pharmacological reviews 344 24928329
2017 The P2X7 receptor: A main player in inflammation. Biochemical pharmacology 331 29288626
2012 Expression of P2X7 receptor increases in vivo tumor growth. Cancer research 319 22505653
2008 P2X7 receptor-Pannexin1 complex: pharmacology and signaling. American journal of physiology. Cell physiology 294 18596211
2018 The Elusive P2X7 Macropore. Trends in cell biology 230 29439897
2012 P2X7 receptors: channels, pores and more. CNS & neurological disorders drug targets 217 22963440
2017 The P2X7 Receptor. Advances in experimental medicine and biology 202 28676924
2015 The P2X7 receptor directly interacts with the NLRP3 inflammasome scaffold protein. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 194 25690658
2019 P2X7 Interactions and Signaling - Making Head or Tail of It. Frontiers in molecular neuroscience 186 31440138
2020 P2X7 receptor and the NLRP3 inflammasome: Partners in crime. Biochemical pharmacology 185 33359010
2011 The human P2X7 receptor and its role in innate immunity. Tissue antigens 164 21988719
2010 Microglia: proliferation and activation driven by the P2X7 receptor. The international journal of biochemistry & cell biology 164 20599520
2017 The P2X7 Receptor-Interleukin-1 Liaison. Frontiers in pharmacology 146 28360855
2017 Neuronal P2X7 Receptors Revisited: Do They Really Exist? The Journal of neuroscience : the official journal of the Society for Neuroscience 142 28747388
2020 P2X7 in Cancer: From Molecular Mechanisms to Therapeutics. Frontiers in pharmacology 138 32581786
2020 The P2X7 Receptor: Central Hub of Brain Diseases. Frontiers in molecular neuroscience 126 32848594
2020 Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology. Molecular psychiatry 122 33328588
2019 P2X7 Receptor Signaling in Stress and Depression. International journal of molecular sciences 115 31174279
2020 P2X7 receptor mediates NLRP3 inflammasome activation in depression and diabetes. Cell & bioscience 114 32166013
2011 Significance of P2X7 receptor variants to human health and disease. Recent patents on DNA & gene sequences 112 21303345
2011 The role of the P2X₇ receptor in infectious diseases. PLoS pathogens 112 22102807
2020 P2X7 Receptors Amplify CNS Damage in Neurodegenerative Diseases. International journal of molecular sciences 106 32825423
2018 Tet1 and Tet2 maintain mesenchymal stem cell homeostasis via demethylation of the P2rX7 promoter. Nature communications 99 29858571
2015 P2X7 on Mouse T Cells: One Channel, Many Functions. Frontiers in immunology 99 26042119
2016 P2X7 Receptor as a Therapeutic Target. Advances in protein chemistry and structural biology 94 27038372
2016 P2X7 receptor antagonists: a patent review (2010-2015). Expert opinion on therapeutic patents 84 27724045
2016 Targeting of the P2X7 receptor in pancreatic cancer and stellate cells. International journal of cancer 80 27513892
2018 P2X7 Receptor: A Potential Therapeutic Target for Depression? Trends in molecular medicine 78 30093269
2008 The P2X7 receptor as a therapeutic target. Expert opinion on therapeutic targets 77 18410246
2020 Paxillin mediates ATP-induced activation of P2X7 receptor and NLRP3 inflammasome. BMC biology 75 33243234
2018 P2RX7 Purinoceptor as a Therapeutic Target-The Second Coming? Frontiers in chemistry 74 30003075
2017 P2X7 receptor antagonism: Implications in diabetic retinopathy. Biochemical pharmacology 72 28479300
2017 Interaction of Purinergic P2X4 and P2X7 Receptor Subunits. Frontiers in pharmacology 70 29213241
2004 Agonists and antagonists acting at P2X7 receptor. Current topics in medicinal chemistry 69 15579103
2014 P2X7 receptor modulates inflammatory and functional pulmonary changes induced by silica. PloS one 61 25310682
2013 P2X7 blockade attenuates mouse liver fibrosis. Molecular medicine reports 61 24247209
2018 P2X7 as a scavenger receptor for innate phagocytosis in the brain. British journal of pharmacology 59 30098011
2015 P2X7 receptors: role in bone cell formation and function. Journal of molecular endocrinology 59 25591582
2020 The Role of P2X7 Receptor in Alzheimer's Disease. Frontiers in molecular neuroscience 58 32581707
2018 Regulation of P2X7 receptor expression and function in the brain. Brain research bulletin 58 30593878
2021 Role of P2X7 Receptors in Immune Responses During Neurodegeneration. Frontiers in cellular neuroscience 57 34122013
2011 P2X7 receptor antagonism in the treatment of cancers. Expert opinion on investigational drugs 56 21619470
2022 Irradiation causes senescence, ATP release, and P2X7 receptor isoform switch in glioblastoma. Cell death & disease 52 35075119
2020 P2X7 Receptor Activity Limits Accumulation of T Cells within Tumors. Cancer research 52 32699136
2019 The role and pharmacological properties of the P2X7 receptor in neuropathic pain. Brain research bulletin 52 31778766
2019 Role of the P2X7 receptor in tumor-associated inflammation. Current opinion in pharmacology 51 30921559
2000 P2X(7) receptor and polykarion formation. Molecular biology of the cell 51 10982408
2021 Involvement of P2X7 receptors in chronic pain disorders. Purinergic signalling 50 34799827
2020 Effect of P2X7 receptor on tumorigenesis and its pharmacological properties. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 50 32004973
2021 Mitochondrial P2X7 Receptor Localization Modulates Energy Metabolism Enhancing Physical Performance. Function (Oxford, England) 48 35330818
2020 The effect of P2X7 on cadmium-induced osteoporosis in mice. Journal of hazardous materials 48 33168313
2013 Associations between depression severity and purinergic receptor P2RX7 gene polymorphisms. Journal of affective disorders 48 23602648
2021 P2X7 Variants in Oncogenesis. Cells 47 33477845
2018 P2RX7-MAPK1/2-SP1 axis inhibits MTOR independent HSPB1-mediated astroglial autophagy. Cell death & disease 47 29749377
2021 P2X7 Receptor-Mediated Inflammation in Cardiovascular Disease. Frontiers in pharmacology 45 33995071
2017 The P2RX7 polymorphism rs2230912 is associated with depression: A meta-analysis. Progress in neuro-psychopharmacology & biological psychiatry 45 29122639
2020 P2X7 Receptor at the Crossroads of T Cell Fate. International journal of molecular sciences 44 32668623
2015 P2X7 receptor as predictor gene for glioma radiosensitivity and median survival. The international journal of biochemistry & cell biology 43 26358881
2020 The P2X7 Receptor as Regulator of T Cell Development and Function. Frontiers in immunology 42 32587592
2014 Lack of association of P2RX7 gene rs2230912 polymorphism with mood disorders: a meta-analysis. PloS one 41 24533115
2022 P2X7 receptor in inflammation and pain. Brain research bulletin 40 35850190
2018 Genetic variation in P2RX7 and pain tolerance. Pain 40 29470314
2015 P2X7 receptor activation regulates rapid unconventional export of transglutaminase-2. Journal of cell science 40 26542019
2019 Pleiotropic Roles of P2X7 in the Central Nervous System. Frontiers in cellular neuroscience 39 31551714
2007 Molecular probes for P2X7 receptor studies. Current medicinal chemistry 39 17584060
2024 The microRNA-211-5p/P2RX7/ERK/GPX4 axis regulates epilepsy-associated neuronal ferroptosis and oxidative stress. Journal of neuroinflammation 38 38191407
2020 CD14 release induced by P2X7 receptor restricts inflammation and increases survival during sepsis. eLife 38 33135636
2019 P2X7 receptor in cardiovascular disease: The heart side. Clinical and experimental pharmacology & physiology 37 30834550
2019 Novel biologics targeting the P2X7 ion channel. Current opinion in pharmacology 37 30986625
2019 Targeting P2X4 and P2X7 receptors in multiple sclerosis. Current opinion in pharmacology 37 31015145
2019 Alternative splicing of P2RX7 pre-messenger RNA in health and diseases: Myth or reality? Biomedical journal 35 31466708
2021 The P2X7 Receptor in Tumor Immunity. Frontiers in cell and developmental biology 34 34239877
2022 Gallic Acid Alleviates Visceral Pain and Depression via Inhibition of P2X7 Receptor. International journal of molecular sciences 33 35682841
2022 Aluminum induces neuroinflammation via P2X7 receptor activating NLRP3 inflammasome pathway. Ecotoxicology and environmental safety 33 36508838
2021 The P2X7 Receptor in Osteoarthritis. Frontiers in cell and developmental biology 33 33644066
2020 P2X7 Receptor Upregulation in Huntington's Disease Brains. Frontiers in molecular neuroscience 33 33122998
2019 Association of purinergic receptor P2RX7 gene polymorphisms with depression symptoms. Progress in neuro-psychopharmacology & biological psychiatry 31 30664971
2024 Role and therapeutic targets of P2X7 receptors in neurodegenerative diseases. Frontiers in immunology 30 38370420
2022 P2RX7 Enhances Tumor Control by CD8+ T Cells in Adoptive Cell Therapy. Cancer immunology research 29 35588154
2019 P2X7 receptor deletion suppresses γ-radiation-induced hyposalivation. American journal of physiology. Regulatory, integrative and comparative physiology 29 30892913
2018 Mechanosensitive Ion Channels: TRPV4 and P2X7 in Disseminating Cancer Cells. Cancer journal (Sudbury, Mass.) 29 29601335
2022 P2X7 Receptor and Purinergic Signaling: Orchestrating Mitochondrial Dysfunction in Neurodegenerative Diseases. eNeuro 28 36376084
2010 Metaanalysis of P2X7 gene polymorphisms and tuberculosis susceptibility. FEMS immunology and medical microbiology 28 20846359
2022 The P2X7 receptor as a new pharmacological target for retinal diseases. Biochemical pharmacology 27 35134386
2019 A Mechanism-Based Approach to P2X7 Receptor Action. Molecular pharmacology 27 30737253
2019 Targeting P2X7 receptors as a means for treating retinal disease. Drug discovery today 27 30954685
2019 The role of microglia and P2X7 receptors in gliomas. Journal of neuroimmunology 27 31031209
2019 Immunomodulatory effects of P2X7 receptor in intracellular parasite infections. Current opinion in pharmacology 26 30901737
2019 P2X7 receptor signaling during adult hippocampal neurogenesis. Neural regeneration research 26 31169175
2013 Natural compounds with P2X7 receptor-modulating properties. Purinergic signalling 25 24163006
2019 P2X7 purinoceptor as a therapeutic target in muscular dystrophies. Current opinion in pharmacology 24 30901735
2019 Critical Role of ATP-P2X7 Axis in UV-Induced Melanogenesis. The Journal of investigative dermatology 24 30926287
2015 Paroxetine suppresses recombinant human P2X7 responses. Purinergic signalling 24 26341077
2023 The P2X7 Receptor, a Multifaceted Receptor in Alzheimer's Disease. International journal of molecular sciences 23 37511507
2021 P2RX7 at the Host-Pathogen Interface of Infectious Diseases. Microbiology and molecular biology reviews : MMBR 23 33441488
2023 The P2X7 Receptor as a Mechanistic Biomarker for Epilepsy. International journal of molecular sciences 22 36982485
2021 The P2X7 Receptor: A Promising Pharmacological Target in Diabetic Retinopathy. International journal of molecular sciences 22 34281162

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