Abstract
The P2X7 receptor is a trimeric ion channel gated by extracellular adenosine 5′-triphosphate. The receptor is present on an increasing number of different cells types including stem, blood, glial, neural, ocular, bone, dental, exocrine, endothelial, muscle, renal and skin cells. The P2X7 receptor induces various downstream events in a cell-specific manner, including inflammatory molecule release, cell proliferation and death, metabolic events, and phagocytosis. As such this receptor plays important roles in heath and disease. Increasing knowledge about the P2X7 receptor has been gained from studies of, but not limited to, protein chemistry including cloning, site-directed mutagenesis, crystal structures and atomic modeling, as well as from studies of primary tissues and transgenic mice. This chapter focuses on the P2X7 receptor itself. This includes the P2RX7 gene and its products including splice and polymorphic variants. This chapter also reviews modulators of P2X7 receptor activation and inhibition, as well as the transcriptional regulation of the P2RX7 gene via its promoter and enhancer regions, and by microRNA and long-coding RNA. Furthermore, this chapter discusses the post-translational modification of the P2X7 receptor by N-linked glycosylation, adenosine 5′-diphosphate ribosylation and palmitoylation. Finally, this chapter reviews interaction partners of the P2X7 receptor, and its cellular localisation and trafficking within cells.
Abbreviations
- ADP:
-
adenosine 5′-diphosphate
- Ano6:
-
anoctamin 6
- ART:
-
ADP-ribosyltransferase
- ATP:
-
adenosine 5′-triphosphate
- BzATP:
-
2′(3′)-O-(4-benzoylbenzoyl) ATP
- HEK:
-
human embryonic kidney
- HSP90:
-
heat shock protein HSP90-β
- IL:
-
interleukin
- lncRNA:
-
long-coding RNA
- LPS:
-
lipopolysaccharide
- miRNA:
-
microRNA
- NAD:
-
nicotinamide adenine dinucleotide
- NMDG+ :
-
N-methyl-D-glucamine
- rs:
-
reference SNP
- SNP:
-
single nucleotide polymorphism
References
Acuna-Castillo C, Coddou C, Bull P, Brito J, Huidobro-Toro JP (2007) Differential role of extracellular histidines in copper, zinc, magnesium and proton modulation of the P2X7 purinergic receptor. J Neurochem 101(1):17–26
Adamczyk M, Griffiths R, Dewitt S, Knauper V, Aeschlimann D (2015) P2X7 receptor activation regulates rapid unconventional export of transglutaminase-2. J Cell Sci 128(24):4615–4628
Adinolfi E, Kim M, Young MT, Di Virgilio F, Surprenant A (2003) Tyrosine phosphorylation of HSP90 within the P2X7 receptor complex negatively regulates P2X7 receptors. J Biol Chem 278(39):37344–37351
Adinolfi E, Pizzirani C, Idzko M, Panther E, Norgauer J, Di Virgilio F, Ferrari D (2005) P2X7 receptor: death or life? Purinergic Signal 1(3):219–227
Adinolfi E, Cirillo M, Woltersdorf R, Falzoni S, Chiozzi P, Pellegatti P, Callegari MG, Sandona D, Markwardt F, Schmalzing G, Di Virgilio F (2010) Trophic activity of a naturally occurring truncated isoform of the P2X7 receptor. FASEB J 24(9):3393–3404
Adriouch S, Dox C, Welge V, Seman M, Koch-Nolte F, Haag F (2002) Cutting edge: a natural P451L mutation in the cytoplasmic domain impairs the function of the mouse P2X7 receptor. J Immunol 169(8):4108–4112
Adriouch S, Dubberke G, Diessenbacher P, Rassendren F, Seman M, Haag F, Koch-Nolte F (2005) Probing the expression and function of the P2X7 purinoceptor with antibodies raised by genetic immunization. Cell Immunol 236(1–2):72–77
Adriouch S, Bannas P, Schwarz N, Fliegert R, Guse AH, Seman M, Haag F, Koch-Nolte F (2008) ADP-ribosylation at R125 gates the P2X7 ion channel by presenting a covalent ligand to its nucleotide binding site. FASEB J 22(3):861–869
Adriouch S, Scheuplein F, Bahring R, Seman M, Boyer O, Koch-Nolte F, Haag F (2009) Characterisation of the R276A gain-of-function mutation in the ectodomain of murine P2X7. Purinergic Signal 5(2):151–161
Agrawal A, Gartland A (2015) P2X7 receptors: role in bone cell formation and function. J Mol Endocrinol 54(2):R75–R88
Ahmadi M, Nowroozi A, Shahlaei M (2015) Constructing an atomic-resolution model of human P2X7 receptor followed by pharmacophore modeling to identify potential inhibitors. J Mol Graph Model 61:243–261
Allsopp RC, Evans RJ (2015) Contribution of the juxtatransmembrane intracellular regions to the time course and permeation of ATP-gated P2X7 receptor ion channels. J Biol Chem 290(23):14556–14566
Allsopp RC, Dayl S, Schmid R, Evans RJ (2017) Unique residues in the ATP gated human P2X7 receptor define a novel allosteric binding pocket for the selective antagonist AZ10606120. Sci Rep 7(1):725
Alves LA, de Melo Reis RA, de Souza CA, de Freitas MS, Teixeira PC, Neto Moreira Ferreira D, Xavier RF (2014) The P2X7 receptor: shifting from a low- to a high-conductance channel – an enigmatic phenomenon? Biochim Biophys Acta 1838(10):2578–2587
Amoroso F, Falzoni S, Adinolfi E, Ferrari D, Di Virgilio F (2012) The P2X7 receptor is a key modulator of aerobic glycolysis. Cell Death Dis 3:e370
Amstrup J, Novak I (2003) P2X7 receptor activates extracellular signal-regulated kinases ERK1 and ERK2 independently of Ca2+ influx. Biochem J 374(Pt 1):51–61
Anderson CM, Nedergaard M (2006) Emerging challenges of assigning P2X7 receptor function and immunoreactivity in neurons. Trends Neurosci 29(5):257–262
Antonio LS, Stewart AP, Xu XJ, Varanda WA, Murrell-Lagnado RD, Edwardson JM (2011) P2X4 receptors interact with both P2X2 and P2X7 receptors in the form of homotrimers. Br J Pharmacol 163(5):1069–1077
Apolloni S, Amadio S, Parisi C, Matteucci A, Potenza RL, Armida M, Popoli P, D’Ambrosi N, Volonte C (2014) Spinal cord pathology is ameliorated by P2X7 antagonism in a SOD1-mutant mouse model of amyotrophic lateral sclerosis. Dis Model Mech 7(9):1101–1109
Aprile-Garcia F, Metzger MW, Paez-Pereda M, Stadler H, Acuna M, Liberman AC, Senin SA, Gerez J, Hoijman E, Refojo D, Mitkovski M, Panhuysen M, Stuhmer W, Holsboer F, Deussing JM, Arzt E (2016) Co-Expression of Wild-Type P2X7R with Gln460Arg Variant Alters Receptor Function. PLoS One 11(3):e0151862
Assandri R, Mazzanti M (1997) Ionic permeability on isolated mouse liver nuclei: influence of ATP and Ca2+. J Membr Biol 157(3):301–309
Atkinson L, Milligan CJ, Buckley NJ, Deuchars J (2002) An ATP-gated ion channel at the cell nucleus. Nature 420(6911):42
Babelova A, Moreth K, Tsalastra-Greul W, Zeng-Brouwers J, Eickelberg O, Young MF, Bruckner P, Pfeilschifter J, Schaefer RM, Grone HJ, Schaefer L (2009) Biglycan, a danger signal that activates the NLRP3 inflammasome via toll-like and P2X receptors. J Biol Chem 284(36):24035–24048
Backlund L, Lavebratt C, Frisen L, Nikamo P, Hukic Sudic D, Traskman-Bendz L, Landen M, Edman G, Vawter MP, Osby U, Schalling M (2012) P2RX7: expression responds to sleep deprivation and associates with rapid cycling in bipolar disorder type 1. PLoS One 7(8):e43057
Bannas P, Adriouch S, Kahl S, Braasch F, Haag F, Koch-Nolte F (2005) Activity and specificity of toxin-related mouse T cell ecto-ADP-ribosyltransferase ART2.2 depends on its association with lipid rafts. Blood 105(9):3663–3670
Barbera-Cremades M, Baroja-Mazo A, Gomez AI, Machado F, Di Virgilio F, Pelegrin P (2012) P2X7 receptor-stimulation causes fever via PGE2 and IL-1beta release. FASEB J 26(7):2951–2962
Barden JA, Sluyter R, Gu BJ, Wiley JS (2003) Specific detection of non-functional human P2X7 receptors in HEK293 cells and B-lymphocytes. FEBS Lett 538(1–3):159–162
Baroni M, Pizzirani C, Pinotti M, Ferrari D, Adinolfi E, Calzavarini S, Caruso P, Bernardi F, Di Virgilio F (2007) Stimulation of P2 (P2X7) receptors in human dendritic cells induces the release of tissue factor-bearing microparticles. FASEB J 21(8):1926–1933
Barth K, Weinhold K, Guenther A, Young MT, Schnittler H, Kasper M (2007) Caveolin-1 influences P2X7 receptor expression and localization in mouse lung alveolar epithelial cells. FEBS J 274(12):3021–3033
Barth K, Weinhold K, Guenther A, Linge A, Gereke M, Kasper M (2008) Characterization of the molecular interaction between caveolin-1 and the P2X receptors 4 and 7 in E10 mouse lung alveolar epithelial cells. Int J Biochem Cell Biol 40(10):2230–2239
Bartlett R, Stokes L, Sluyter R (2014) The P2X7 receptor channel: recent developments and the use of P2X7 antagonists in models of disease. Pharmacol Rev 66(3):638–675
Bartlett R, Sluyter V, Watson D, Sluyter R, Yerbury JJ (2017) P2X7 antagonism using Brilliant Blue G reduces body weight loss and prolongs survival in female SOD1G93A amyotrophic lateral sclerosis mice. PeerJ 5:e3064
Basso AM, Bratcher NA, Harris RR, Jarvis MF, Decker MW, Rueter LE (2009) Behavioral profile of P2X7 receptor knockout mice in animal models of depression and anxiety: relevance for neuropsychiatric disorders. Behav Brain Res 198(1):83–90
Bauernfeind FG, Horvath G, Stutz A, Alnemri ES, MacDonald K, Speert D, Fernandes-Alnemri T, Wu J, Monks BG, Fitzgerald KA, Hornung V, Latz E (2009) Cutting edge: NF-kappaB activating pattern recognition and cytokine receptors license NLRP3 inflammasome activation by regulating NLRP3 expression. J Immunol 183(2):787–791
Beaucage KL, Xiao A, Pollmann SI, Grol MW, Beach RJ, Holdsworth DW, Sims SM, Darling MR, Dixon SJ (2014) Loss of P2X7 nucleotide receptor function leads to abnormal fat distribution in mice. Purinergic Signal 10(2):291–304
Beigi RD, Kertesy SB, Aquilina G, Dubyak GR (2003) Oxidized ATP (oATP) attenuates proinflammatory signaling via P2 receptor-independent mechanisms. Br J Pharmacol 140(3):507–519
Bhaskaracharya A, Dao-Ung P, Jalilian I, Spildrejorde M, Skarratt KK, Fuller SJ, Sluyter R, Stokes L (2014) Probenecid blocks human P2X7 receptor-induced dye uptake via a pannexin-1 independent mechanism. PLoS One 9(3):e93058
Bhattacharya A, Biber K (2016) The microglial ATP-gated ion channel P2X7 as a CNS drug target. Glia 64(10):1772–1787
Bhattacharya A, Wang Q, Ao H, Shoblock JR, Lord B, Aluisio L, Fraser I, Nepomuceno D, Neff RA, Welty N, Lovenberg TW, Bonaventure P, Wickenden AD, Letavic MA (2013) Pharmacological characterization of a novel centrally permeable P2X7 receptor antagonist: JNJ-47965567. Br J Pharmacol 170(3):624–640
Bianchi BR, Lynch KJ, Touma E, Niforatos W, Burgard EC, Alexander KM, Park HS, Yu H, Metzger R, Kowaluk E, Jarvis MF, van Biesen T (1999) Pharmacological characterization of recombinant human and rat P2X receptor subtypes. Eur J Pharmacol 376(1–2):127–138
Bilodeau MS, Arguin G, Gendron FP (2015) C/EBPbeta regulates P2X7 receptor expression in response to glucose challenge in intestinal epithelial cells. Biochem Cell Biol 93(1):38–46
Biswas D, Qureshi OS, Lee WY, Croudace JE, Mura M, Lammas DA (2008) ATP-induced autophagy is associated with rapid killing of intracellular mycobacteria within human monocytes/macrophages. BMC Immunol 9:35
Bo X, Jiang LH, Wilson HL, Kim M, Burnstock G, Surprenant A, North RA (2003) Pharmacological and biophysical properties of the human P2X5 receptor. Mol Pharmacol 63(6):1407–1416
Boldrini L, Giordano M, Ali G, Melfi F, Romano G, Lucchi M, Fontanini G (2015) P2X7 mRNA expression in non-small cell lung cancer: microRNA regulation and prognostic value. Oncol Lett 9(1):449–453
Booth JW, Tam FW, Unwin RJ (2012) P2 purinoceptors: renal pathophysiology and therapeutic potential. Clin Nephrol 78(2):154–163
Boue-Grabot E, Archambault V, Seguela P (2000) A protein kinase C site highly conserved in P2X subunits controls the desensitization kinetics of P2X2 ATP-gated channels. J Biol Chem 275(14):10190–10195
Boumechache M, Masin M, Edwardson JM, Gorecki DC, Murrell-Lagnado R (2009) Analysis of assembly and trafficking of native P2X4 and P2X7 receptor complexes in rodent immune cells. J Biol Chem 284(20):13446–13454
Boyce AK, Kim MS, Wicki-Stordeur LE, Swayne LA (2015) ATP stimulates pannexin 1 internalization to endosomal compartments. Biochem J 470(3):319–330
Bradley HJ, Liu X, Collins V, Owide J, Goli GR, Smith M, Surprenant A, White SJ, Jiang LH (2010) Identification of an intracellular microdomain of the P2X7 receptor that is crucial in basolateral membrane targeting in epithelial cells. FEBS Lett 584(23):4740–4744
Bradley HJ, Browne LE, Yang W, Jiang LH (2011a) Pharmacological properties of the rhesus macaque monkey P2X7 receptor. Br J Pharmacol 164(2b):743–754
Bradley HJ, Baldwin JM, Goli GR, Johnson B, Zou J, Sivaprasadarao A, Baldwin SA, Jiang LH (2011b) Residues 155 and 348 contribute to the determination of P2X7 receptor function via distinct mechanisms revealed by single-nucleotide polymorphisms. J Biol Chem 286(10):8176–8187
Browne LE, Compan V, Bragg L, North RA (2013) P2X7 receptor channels allow direct permeation of nanometer-sized dyes. J Neurosci 33(8):3557–3566
Buell GN, Talabot F, Gos A, Lorenz J, Lai E, Morris MA, Antonarakis SE (1998a) Gene structure and chromosomal localization of the human P2X7 receptor. Receptors Channels 5(6):347–354
Buell G, Chessell IP, Michel AD, Collo G, Salazzo M, Herren S, Gretener D, Grahames C, Kaur R, Kosco-Vilbois MH, Humphrey PP (1998b) Blockade of human P2X7 receptor function with a monoclonal antibody. Blood 92(10):3521–3528
Burnstock G (2015) Intracellular expression of purinoceptors. Purinergic Signal 11(3):275–276
Burnstock G, Kennedy C (2011) P2X receptors in health and disease. Adv Pharmacol 61:333–372
Burnstock G, Ralevic V (2014) Purinergic signaling and blood vessels in health and disease. Pharmacol Rev 66(1):102–192
Cabrini G, Falzoni S, Forchap SL, Pellegatti P, Balboni A, Agostini P, Cuneo A, Castoldi G, Baricordi OR, Di Virgilio F (2005) A His-155 to Tyr polymorphism confers gain-of-function to the human P2X7 receptor of human leukemic lymphocytes. J Immunol 175(1):82–89
Caseley EA, Muench SP, Roger S, Mao HJ, Baldwin SA, Jiang LH (2014) Non-synonymous single nucleotide polymorphisms in the P2X receptor genes: association with diseases, impact on receptor functions and potential use as diagnosis biomarkers. Int J Mol Sci 15(8):13344–13371
Cesaro A, Brest P, Hofman V, Hebuterne X, Wildman S, Ferrua B, Marchetti S, Doglio A, Vouret-Craviari V, Galland F, Naquet P, Mograbi B, Unwin R, Hofman P (2010) Amplification loop of the inflammatory process is induced by P2X7R activation in intestinal epithelial cells in response to neutrophil transepithelial migration. Am J Physiol Gastrointest Liver Physiol 299(1):G32–G42
Chakfe Y, Seguin R, Antel JP, Morissette C, Malo D, Henderson D, Seguela P (2002) ADP and AMP induce interleukin-1beta release from microglial cells through activation of ATP-primed P2X7 receptor channels. J Neurosci 22(8):3061–3069
Chaumont S, Jiang LH, Penna A, North RA, Rassendren F (2004) Identification of a trafficking motif involved in the stabilization and polarization of P2X receptors. J Biol Chem 279(28):29628–29638
Cheewatrakoolpong B, Gilchrest H, Anthes JC, Greenfeder S (2005) Identification and characterization of splice variants of the human P2X7 ATP channel. Biochem Biophys Res Commun 332(1):17–27
Chekeni FB, Elliott MR, Sandilos JK, Walk SF, Kinchen JM, Lazarowski ER, Armstrong AJ, Penuela S, Laird DW, Salvesen GS, Isakson BE, Bayliss DA, Ravichandran KS (2010) Pannexin 1 channels mediate ‘find-me’ signal release and membrane permeability during apoptosis. Nature 467(7317):863–867
Chen Q, Jin Y, Zhang K, Li H, Chen W, Meng G, Fang X (2014) Alarmin HNP-1 promotes pyroptosis and IL-1beta release through different roles of NLRP3 inflammasome via P2X7 in LPS-primed macrophages. Innate Immun 20(3):290–300
Chessell IP, Simon J, Hibell AD, Michel AD, Barnard EA, Humphrey PP (1998) Cloning and functional characterisation of the mouse P2X7 receptor. FEBS Lett 439(1–2):26–30
Chessell IP, Hatcher JP, Bountra C, Michel AD, Hughes JP, Green P, Egerton J, Murfin M, Richardson J, Peck WL, Grahames CB, Casula MA, Yiangou Y, Birch R, Anand P, Buell GN (2005) Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain. Pain 114(3):386–396
Chong JH, Zheng GG, Ma YY, Zhang HY, Nie K, Lin YM, Wu KF (2010) The hyposensitive N187D P2X7 mutant promotes malignant progression in nude mice. J Biol Chem 285(46):36179–36187
Cockcroft S, Gomperts BD (1979) ATP induces nucleotide permeability in rat mast cells. Nature 279(5713):541–542
Cockcroft S, Gomperts BD (1980) The ATP4- receptor of rat mast cells. Biochem J 188(3):789–798
Collo G, Neidhart S, Kawashima E, Kosco-Vilbois M, North RA, Buell G (1997) Tissue distribution of the P2X7 receptor. Neuropharmacology 36(9):1277–1283
Compan V, Ulmann L, Stelmashenko O, Chemin J, Chaumont S, Rassendren F (2012) P2X2 and P2X5 subunits define a new heteromeric receptor with P2X7-like properties. J Neurosci 32(12):4284–4296
Connon CJ, Young RD, Kidd EJ (2003) P2X7 receptors are redistributed on human monocytes after pore formation in response to prolonged agonist exposure. Pharmacology 67(3):163–168
Costa-Junior HM, Sarmento Vieira F, Coutinho-Silva R (2011) C terminus of the P2X7 receptor: treasure hunting. Purinergic Signal 7(1):7–19
Dagvadorj J, Shimada K, Chen S, Jones HD, Tumurkhuu G, Zhang W, Wawrowsky KA, Crother TR, Arditi M (2015) Lipopolysaccharide induces alveolar macrophage necrosis via CD14 and the P2X7 receptor leading to interleukin-1alpha release. Immunity 42(4):640–653
Danquah W, Meyer-Schwesinger C, Rissiek B, Pinto C, Serracant-Prat A, Amadi M, Iacenda D, Knop JH, Hammel A, Bergmann P, Schwarz N, Assuncao J, Rotthier W, Haag F, Tolosa E, Bannas P, Boue-Grabot E, Magnus T, Laeremans T, Stortelers C, Koch-Nolte F (2016) Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation. Sci Transl Med 8(366):366ra162
De Marchi E, Orioli E, Dal Ben D, Adinolfi E (2016) P2X7 eceptor as a therapeutic target. Adv Protein Chem Struct Biol 104:39–79
Deniz E, Erman B (2017) Long noncoding RNA (lincRNA), a new paradigm in gene expression control. Funct Integr Genomics 17(2–3):135–143
Denlinger LC, Fisette PL, Sommer JA, Watters JJ, Prabhu U, Dubyak GR, Proctor RA, Bertics PJ (2001) Cutting edge: the nucleotide receptor P2X7 contains multiple protein- and lipid-interaction motifs including a potential binding site for bacterial lipopolysaccharide. J Immunol 167(4):1871–1876
Denlinger LC, Sommer JA, Parker K, Gudipaty L, Fisette PL, Watters JW, Proctor RA, Dubyak GR, Bertics PJ (2003) Mutation of a dibasic amino acid motif within the C terminus of the P2X7 nucleotide receptor results in trafficking defects and impaired function. J Immunol 171(3):1304–1311
Denlinger LC, Coursin DB, Schell K, Angelini G, Green DN, Guadarrama AG, Halsey J, Prabhu U, Hogan KJ, Bertics PJ (2006) Human P2X7 pore function predicts allele linkage disequilibrium. Clin Chem 52(6):995–1004
Donnelly-Roberts DL, Namovic MT, Han P, Jarvis MF (2009a) Mammalian P2X7 receptor pharmacology: comparison of recombinant mouse, rat and human P2X7 receptors. Br J Pharmacol 157(7):1203–1214
Donnelly-Roberts DL, Namovic MT, Surber B, Vaidyanathan SX, Perez-Medrano A, Wang Y, Carroll WA, Jarvis MF (2009b) [3H]A-804598 ([3H]2-cyano-1-[(1S)-1-phenylethyl]-3-quinolin-5-ylguanidine) is a novel, potent, and selective antagonist radioligand for P2X7 receptors. Neuropharmacology 56(1):223–229
Dubyak GR (2009) Both sides now: multiple interactions of ATP with pannexin-1 hemichannels. Focus on “A permeant regulating its permeation pore: inhibition of pannexin 1 channels by ATP”. Am J Physiol Cell Physiol 296(2):C235–C241
Dubyak GR (2012) P2X7 receptor regulation of non-classical secretion from immune effector cells. Cell Microbiol 14(11):1697–1706
Elssner A, Duncan M, Gavrilin M, Wewers MD (2004) A novel P2X7 receptor activator, the human cathelicidin-derived peptide LL37, induces IL-1 beta processing and release. J Immunol 172(8):4987–4994
Engel T, Brennan GP, Sanz-Rodriguez A, Alves M, Beamer E, Watters O, Henshall DC, Jimenez-Mateos EM (2017) A calcium-sensitive feed-forward loop regulating the expression of the ATP-gated purinergic P2X7 receptor via specificity protein 1 and microRNA-22. Biochim Biophys Acta 1864(2):255–266
Eser A, Colombel JF, Rutgeerts P, Vermeire S, Vogelsang H, Braddock M, Persson T, Reinisch W (2015) Safety and efficacy of an oral inhibitor of the purinergic receptor P2X7 in adult patients with moderately to severely active Crohn’s disease: a randomized placebo-controlled, double-blind, phase IIa study. Inflamm Bowel Dis 21(10):2247–2253
Evans RJ, Lewis C, Buell G, Valera S, North RA, Surprenant A (1995) Pharmacological characterization of heterologously expressed ATP-gated cation channels (P2x purinoceptors). Mol Pharmacol 48(2):178–183
Fairbairn IP, Stober CB, Kumararatne DS, Lammas DA (2001) ATP-mediated killing of intracellular mycobacteria by macrophages is a P2X7-dependent process inducing bacterial death by phagosome-lysosome fusion. J Immunol 167(6):3300–3307
Fang KM, Yang CS, Sun SH, Tzeng SF (2009) Microglial phagocytosis attenuated by short-term exposure to exogenous ATP through P2X receptor action. J Neurochem 111(5):1225–1237
Faulks M, Kuit TA, Sophocleous RA, Curtis BL, Curtis SJ, Jurak LM, Sluyter R (2016) P2X7 receptor activation causes phosphatidylserine exposure in canine erythrocytes. World J Hematol 5(4):88–93
Feng YH, Wang L, Wang Q, Li X, Zeng R, Gorodeski GI (2005) ATP stimulates GRK-3 phosphorylation and beta-arrestin-2-dependent internalization of P2X7 receptor. Am J Physiol Cell Physiol 288(6):C1342–C1356
Feng YH, Li X, Wang L, Zhou L, Gorodeski GI (2006) A truncated P2X7 receptor variant (P2X7-j) endogenously expressed in cervical cancer cells antagonizes the full-length P2X7 receptor through hetero-oligomerization. J Biol Chem 281(25):17228–17237
Feng JF, Gao XF, Pu YY, Burnstock G, Xiang Z, He C (2015) P2X7 receptors and Fyn kinase mediate ATP-induced oligodendrocyte progenitor cell migration. Purinergic Signal 11(3):361–369
Ferrari D, Pizzirani C, Adinolfi E, Forchap S, Sitta B, Turchet L, Falzoni S, Minelli M, Baricordi R, Di Virgilio F (2004) The antibiotic polymyxin B modulates P2X7 receptor function. J Immunol 173(7):4652–4660
Ferrari D, Bianchi N, Eltzschig HK, Gambari R (2016) MicroRNAs Modulate the Purinergic Signaling Network. Trends Mol Med 22(10):905–918
Fonfria E, Clay WC, Levy DS, Goodwin JA, Roman S, Smith GD, Condreay JP, Michel AD (2008) Cloning and pharmacological characterization of the guinea pig P2X7 receptor orthologue. Br J Pharmacol 153(3):544–556
Franceschini A, Capece M, Chiozzi P, Falzoni S, Sanz JM, Sarti AC, Bonora M, Pinton P, Di Virgilio F (2015) The P2X7 receptor directly interacts with the NLRP3 inflammasome scaffold protein. FASEB J 29(6):2450–2461
Franco MC, Ye Y, Refakis CA, Feldman JL, Stokes AL, Basso M, Melero Fernandez de Mera RM, Sparrow NA, Calingasan NY, Kiaei M, Rhoads TW, Ma TC, Grumet M, Barnes S, Beal MF, Beckman JS, Mehl R, Estevez AG (2013) Nitration of Hsp90 induces cell death. Proc Natl Acad Sci U S A 110(12):E1102–E1111
Fuller SJ, Stokes L, Skarratt KK, Gu BJ, Wiley JS (2009) Genetics of the P2X7 receptor and human disease. Purinergic Signal 5(2):257–262
Furlan-Freguia C, Marchese P, Gruber A, Ruggeri ZM, Ruf W (2011) P2X7 receptor signaling contributes to tissue factor-dependent thrombosis in mice. J Clin Invest 121(7):2932–2944
Gangadharan V, Nohe A, Caplan J, Czymmek K, Duncan RL (2015) Caveolin-1 regulates P2X7 receptor signaling in osteoblasts. Am J Physiol Cell Physiol 308(1):C41–C50
Garcia-Huerta P, Diaz-Hernandez M, Delicado EG, Pimentel-Santillana M, Miras-Portugal MT, Gomez-Villafuertes R (2012) The specificity protein factor Sp1 mediates transcriptional regulation of P2X7 receptors in the nervous system. J Biol Chem 287(53):44628–44644
Garcia-Marcos M, Pochet S, Tandel S, Fontanils U, Astigarraga E, Fernandez-Gonzalez JA, Kumps A, Marino A, Dehaye JP (2006a) Characterization and comparison of raft-like membranes isolated by two different methods from rat submandibular gland cells. Biochim Biophys Acta 1758(6):796–806
Garcia-Marcos M, Perez-Andres E, Tandel S, Fontanils U, Kumps A, Kabre E, Gomez-Munoz A, Marino A, Dehaye JP, Pochet S (2006b) Coupling of two pools of P2X7 receptors to distinct intracellular signaling pathways in rat submandibular gland. J Lipid Res 47(4):705–714
Garcia-Marcos M, Dehaye JP, Marino A (2009) Membrane compartments and purinergic signalling: the role of plasma membrane microdomains in the modulation of P2XR-mediated signalling. FEBS J 276(2):330–340
Geraghty NJ, Watson D, Adhikary SR, Sluyter R (2016) P2X7 receptor in skin biology and diseases. World J Dermatol 5(2):72–83
Gilbert SM, Gidley Baird A, Glazer S, Barden JA, Glazer A, Teh LC, King J (2017) A Phase 1 clinical trial demonstrates nfP2X7 targeted antibodies provide a novel, safe and tolerable topical therapy for BCC. Br J Dermatol doi: 10.1111/bjd.15364
Giuliani AL, Sarti AC, Falzoni S, Di Virgilio F (2017) The P2X7 Receptor-Interleukin-1 Liaison. Front Pharmacol 8:123
Glaser T, de Oliveira SL, Cheffer A, Beco R, Martins P, Fornazari M, Lameu C, Junior HM, Coutinho-Silva R, Ulrich H (2014) Modulation of mouse embryonic stem cell proliferation and neural differentiation by the P2X7 receptor. PLoS One 9(5):e96281
Gomez-Villafuertes R, Garcia-Huerta P, Diaz-Hernandez JI, Miras-Portugal MT (2015) PI3K/Akt signaling pathway triggers P2X7 receptor expression as a pro-survival factor of neuroblastoma cells under limiting growth conditions. Sci Rep 5:18417
Gonnord P, Delarasse C, Auger R, Benihoud K, Prigent M, Cuif MH, Lamaze C, Kanellopoulos JM (2009) Palmitoylation of the P2X7 receptor, an ATP-gated channel, controls its expression and association with lipid rafts. FASEB J 23(3):795–805
Gordon JL (1986) Extracellular ATP: effects, sources and fate. Biochem J 233(2):309–319
Grol MW, Zelner I, Dixon SJ (2012) P2X7-mediated calcium influx triggers a sustained, PI3K-dependent increase in metabolic acid production by osteoblast-like cells. Am J Physiol Endocrinol Metab 302(5):E561–E575
Groschel-Stewart U, Bardini M, Robson T, Burnstock G (1999) Localisation of P2X5 and P2X7 receptors by immunohistochemistry in rat stratified squamous epithelia. Cell Tissue Res 296(3):599–605
Gu BJ, Wiley JS (2006) Rapid ATP-induced release of matrix metalloproteinase 9 is mediated by the P2X7 receptor. Blood 107(12):4946–4953
Gu BJ, Zhang WY, Bendall LJ, Chessell IP, Buell GN, Wiley JS (2000) Expression of P2X7 purinoceptors on human lymphocytes and monocytes: evidence for nonfunctional P2X7 receptors. Am J Physiol Cell Physiol 279(4):C1189–C1197
Gu BJ, Zhang W, Worthington RA, Sluyter R, Dao-Ung P, Petrou S, Barden JA, Wiley JS (2001) A Glu-496 to Ala polymorphism leads to loss of function of the human P2X7 receptor. J Biol Chem 276(14):11135–11142
Gu BJ, Rathsam C, Stokes L, McGeachie AB, Wiley JS (2009) Extracellular ATP dissociates nonmuscle myosin from P2X7 complex: this dissociation regulates P2X7 pore formation. Am J Physiol Cell Physiol 297(2):C430–C439
Gu BJ, Saunders BM, Jursik C, Wiley JS (2010) The P2X7-nonmuscle myosin membrane complex regulates phagocytosis of nonopsonized particles and bacteria by a pathway attenuated by extracellular ATP. Blood 115(8):1621–1631
Gu BJ, Saunders BM, Petrou S, Wiley JS (2011) P2X7 is a scavenger receptor for apoptotic cells in the absence of its ligand, extracellular ATP. J Immunol 187(5):2365–2375
Gu BJ, Baird PN, Vessey KA, Skarratt KK, Fletcher EL, Fuller SJ, Richardson AJ, Guymer RH, Wiley JS (2013) A rare functional haplotype of the P2RX4 and P2RX7 genes leads to loss of innate phagocytosis and confers increased risk of age-related macular degeneration. FASEB J 27(4):1479–1487
Gu BJ, Field J, Dutertre S, Ou A, Kilpatrick TJ, Lechner-Scott J, Scott R, Lea R, Taylor BV, Stankovich J, Butzkueven H, Gresle M, Laws SM, Petrou S, Hoffjan S, Akkad DA, Graham CA, Hawkins S, Glaser A, Bedri SK, Hillert J, Matute C, Antiguedad A, Wiley JS (2015a) A rare P2X7 variant Arg307Gln with absent pore formation function protects against neuroinflammation in multiple sclerosis. Hum Mol Genet 24(19):5644–5654
Gu BJ, Lovelace MD, Weible MW, 2nd, Allen DG, Eamegdool SS, Chan-Ling T, Wiley JS (2015b) P2X7 is an archaic scavenger receptor recognizing apoptotic neuroblasts in early human neurogenesis. Recept Clin Investig 2:e699
Gudipaty L, Humphreys BD, Buell G, Dubyak GR (2001) Regulation of P2X7 nucleotide receptor function in human monocytes by extracellular ions and receptor density. Am J Physiol Cell Physiol 280(4):C943–C953
Guo C, Masin M, Qureshi OS, Murrell-Lagnado RD (2007) Evidence for functional P2X4/P2X7 heteromeric receptors. Mol Pharmacol 72(6):1447–1456
Guzman-Aranguez A, Perez de Lara MJ, Pintor J (2017) Hyperosmotic stress induces ATP release and changes in P2X7 receptor levels in human corneal and conjunctival epithelial cells. Purinergic Signal 13(2):249–258
Haanes KA, Schwab A, Novak I (2012) The P2X7 receptor supports both life and death in fibrogenic pancreatic stellate cells. PLoS One 7(12):e51164
Hanley PJ, Kronlage M, Kirschning C, del Rey A, Di Virgilio F, Leipziger J, Chessell IP, Sargin S, Filippov MA, Lindemann O, Mohr S, Konigs V, Schillers H, Bahler M, Schwab A (2012) Transient P2X7 receptor activation triggers macrophage death independent of Toll-like receptors 2 and 4, caspase-1, and pannexin-1 proteins. J Biol Chem 287(13):10650–10663
Hashimoto-Hill S, Friesen L, Kim M, Kim CH (2017) Contraction of intestinal effector T cells by retinoic acid-induced purinergic receptor P2X7. Mucosal Immunol 10(4):912–923
Hattori M, Gouaux E (2012) Molecular mechanism of ATP binding and ion channel activation in P2X receptors. Nature 485(7397):207–212
He YQ, Chen J, Lu XJ, Shi YH (2013) Characterization of P2X7R and its function in the macrophages of ayu, Plecoglossus altivelis. PLoS One 8(2):e57505
Hedden L, Benes CH, Soltoff SP (2011) P2X7 receptor antagonists display agonist-like effects on cell signaling proteins. Biochim Biophys Acta 1810(5):532–542
Heiss K, Janner N, Mahnss B, Schumacher V, Koch-Nolte F, Haag F, Mittrucker HW (2008) High sensitivity of intestinal CD8+ T cells to nucleotides indicates P2X7 as a regulator for intestinal T cell responses. J Immunol 181(6):3861–3869
Helliwell RM, ShioukHuey CO, Dhuna K, Molero JC, Ye JM, Xue CC, Stokes L (2015) Selected ginsenosides of the protopanaxdiol series are novel positive allosteric modulators of P2X7 receptors. Br J Pharmacol 172(13):3326–3340
Hibell AD, Thompson KM, Xing M, Humphrey PP, Michel AD (2001) Complexities of measuring antagonist potency at P2X7 receptor orthologs. J Pharmacol Exp Ther 296(3):947–957
Hong S, Schwarz N, Brass A, Seman M, Haag F, Koch-Nolte F, Schilling WP, Dubyak GR (2009) Differential regulation of P2X7 receptor activation by extracellular nicotinamide adenine dinucleotide and ecto-ADP-ribosyltransferases in murine macrophages and T cells. J Immunol 183(1):578–592
Honore P, Donnelly-Roberts D, Namovic MT, Hsieh G, Zhu CZ, Mikusa JP, Hernandez G, Zhong C, Gauvin DM, Chandran P, Harris R, Medrano AP, Carroll W, Marsh K, Sullivan JP, Faltynek CR, Jarvis MF (2006) 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. J Pharmacol Exp Ther 319(3):1376–1385
Huang S, Chen Y, Wu W, Ouyang N, Chen J, Li H, Liu X, Su F, Lin L, Yao Y (2013) miR-150 promotes human breast cancer growth and malignant behavior by targeting the pro-apoptotic purinergic P2X7 receptor. PLoS One 8(12):e80707
Hung SC, Choi CH, Said-Sadier N, Johnson L, Atanasova KR, Sellami H, Yilmaz O, Ojcius DM (2013) P2X4 assembles with P2X7 and pannexin-1 in gingival epithelial cells and modulates ATP-induced reactive oxygen species production and inflammasome activation. PLoS One 8(7):e70210
Husted LB, Harslof T, Stenkjaer L, Carstens M, Jorgensen NR, Langdahl BL (2013) Functional polymorphisms in the P2X7 receptor gene are associated with osteoporosis. Osteoporos Int 24(3):949–959
Ide S, Nishizawa D, Fukuda K, Kasai S, Hasegawa J, Hayashida M, Minami M, Ikeda K (2014) Haplotypes of P2RX7 gene polymorphisms are associated with both cold pain sensitivity and analgesic effect of fentanyl. Mol Pain 10:75
Iglesias R, Locovei S, Roque A, Alberto AP, Dahl G, Spray DC, Scemes E (2008) P2X7 receptor-Pannexin1 complex: pharmacology and signaling. Am J Physiol Cell Physiol 295(3):C752–C760
Jacob F, Perez Novo C, Bachert C, Van Crombruggen K (2013) Purinergic signaling in inflammatory cells: P2 receptor expression, functional effects, and modulation of inflammatory responses. Purinergic Signal 9(3):285–306
Jiang LH, Mackenzie AB, North RA, Surprenant A (2000) Brilliant blue G selectively blocks ATP-gated rat P2X7 receptors. Mol Pharmacol 58(1):82–88
Jiang LH, Rassendren F, Mackenzie A, Zhang YH, Surprenant A, North RA (2005) N-methyl-D-glucamine and propidium dyes utilize different permeation pathways at rat P2X7 receptors. Am J Physiol Cell Physiol 289(5):C1295–C1302
Jiang H, Zhu AG, Mamczur M, Falck JR, Lerea KM, McGiff JC (2007) Stimulation of rat erythrocyte P2X7 receptor induces the release of epoxyeicosatrienoic acids. Br J Pharmacol 151(7):1033–1040
Jiang LH, Baldwin JM, Roger S, Baldwin SA (2013) Insights into the molecular mechanisms underlying mammalian P2X7 receptor functions and contributions in diseases, revealed by structural modeling and single nucleotide polymorphisms. Front Pharmacol 4:55
Jiang W, Lv H, Wang H, Wang D, Sun S, Jia Q, Wang P, Song B, Ni L (2015a) Activation of the NLRP3/caspase-1 inflammasome in human dental pulp tissue and human dental pulp fibroblasts. Cell Tissue Res 361(2):541–555
Jiang T, Hoekstra J, Heng X, Kang W, Ding J, Liu J, Chen S, Zhang J (2015b) P2X7 receptor is critical in alpha-synuclein--mediated microglial NADPH oxidase activation. Neurobiol Aging 36(7):2304–2318
Jiang LH, Hao Y, Mousawi F, Peng H, Yang X (2017) Expression of P2 purinergic receptors in mesenchymal stem cells and their roles in extracellular nucleotide regulation of cell functions. J Cell Physiol 232(2):287–297
Jimenez-Mateos EM, Arribas-Blazquez M, Sanz-Rodriguez A, Concannon C, Olivos-Ore LA, Reschke CR, Mooney CM, Mooney C, Lugara E, Morgan J, Langa E, Jimenez-Pacheco A, Silva LF, Mesuret G, Boison D, Miras-Portugal MT, Letavic M, Artalejo AR, Bhattacharya A, Diaz-Hernandez M, Henshall DC, Engel T (2015) microRNA targeting of the P2X7 purinoceptor opposes a contralateral epileptogenic focus in the hippocampus. Sci Rep 5:17486
Jindrichova M, Kuzyk P, Li S, Stojilkovic SS, Zemkova H (2012) Conserved ectodomain cysteines are essential for rat P2X7 receptor trafficking. Purinergic Signal 8(2):317–325
Jorgensen NR, Husted LB, Skarratt KK, Stokes L, Tofteng CL, Kvist T, Jensen JE, Eiken P, Brixen K, Fuller S, Clifton-Bligh R, Gartland A, Schwarz P, Langdahl BL, Wiley JS (2012) Single-nucleotide polymorphisms in the P2X7 receptor gene are associated with post-menopausal bone loss and vertebral fractures. Eur J Hum Genet 20(6):675–681
Kanjanamekanant K, Luckprom P, Pavasant P (2014) P2X7 receptor-Pannexin1 interaction mediates stress-induced interleukin-1 beta expression in human periodontal ligament cells. J Periodontal Res 49(5):595–602
Karasawa A, Kawate T (2016) Structural basis for subtype-specific inhibition of the P2X7 receptor. elife 5:e22153
Kasuya G, Fujiwara Y, Takemoto M, Dohmae N, Nakada-Nakura Y, Ishitani R, Hattori M, Nureki O (2016) Structural insights into divalent cation modulations of ATP-gated P2X receptor channels. Cell Rep 14(4):932–944
Kawano A, Tsukimoto M, Mori D, Noguchi T, Harada H, Takenouchi T, Kitani H, Kojima S (2012a) Regulation of P2X7-dependent inflammatory functions by P2X4 receptor in mouse macrophages. Biochem Biophys Res Commun 420(1):102–107
Kawano A, Tsukimoto M, Noguchi T, Hotta N, Harada H, Takenouchi T, Kitani H, Kojima S (2012b) Involvement of P2X4 receptor in P2X7 receptor-dependent cell death of mouse macrophages. Biochem Biophys Res Commun 419(2):374–380
Kawate T, Michel JC, Birdsong WT, Gouaux E (2009) Crystal structure of the ATP-gated P2X4 ion channel in the closed state. Nature 460(7255):592–598
Keller R (1966) Tissue mast cells in immune reactions. Monogr Allergy 2:1–144
Keystone EC, Wang MM, Layton M, Hollis S, McInnes IB (2012) Clinical evaluation of the efficacy of the P2X7 purinergic receptor antagonist AZD9056 on the signs and symptoms of rheumatoid arthritis in patients with active disease despite treatment with methotrexate or sulphasalazine. Ann Rheum Dis 71(10):1630–1635
Khadra A, Tomic M, Yan Z, Zemkova H, Sherman A, Stojilkovic SS (2013) Dual gating mechanism and function of P2X7 receptor channels. Biophys J 104(12):2612–2621
Khakh BS, Bao XR, Labarca C, Lester HA (1999) Neuronal P2X transmitter-gated cation channels change their ion selectivity in seconds. Nat Neurosci 2(4):322–330
Kido Y, Kawahara C, Terai Y, Ohishi A, Kobayashi S, Hayakawa M, Kamatsuka Y, Nishida K, Nagasawa K (2014) Regulation of activity of P2X7 receptor by its splice variants in cultured mouse astrocytes. Glia 62(3):440–451
Kim M, Jiang LH, Wilson HL, North RA, Surprenant A (2001) Proteomic and functional evidence for a P2X7 receptor signalling complex. EMBO J 20(22):6347–6358
Klapperstuck M, Buttner C, Nickel P, Schmalzing G, Lambrecht G, Markwardt F (2000) Antagonism by the suramin analogue NF279 on human P2X1 and P2X7 receptors. Eur J Pharmacol 387(3):245–252
Kucenas S, Li Z, Cox JA, Egan TM, Voigt MM (2003) Molecular characterization of the zebrafish P2X receptor subunit gene family. Neuroscience 121(4):935–945
Kuehnel MP, Rybin V, Anand PK, Anes E, Griffiths G (2009a) Lipids regulate P2X7-receptor-dependent actin assembly by phagosomes via ADP translocation and ATP synthesis in the phagosome lumen. J Cell Sci 122(Pt 4):499–504
Kuehnel MP, Reiss M, Anand PK, Treede I, Holzer D, Hoffmann E, Klapperstueck M, Steinberg TH, Markwardt F, Griffiths G (2009b) Sphingosine-1-phosphate receptors stimulate macrophage plasma-membrane actin assembly via ADP release, ATP synthesis and P2X7R activation. J Cell Sci 122(Pt 4):505–512
Kunzelmann K, Nilius B, Owsianik G, Schreiber R, Ousingsawat J, Sirianant L, Wanitchakool P, Bevers EM, Heemskerk JW (2014) Molecular functions of anoctamin 6 (TMEM16F): a chloride channel, cation channel, or phospholipid scramblase? Pflugers Arch 466(3):407–414
Kurashima Y, Amiya T, Nochi T, Fujisawa K, Haraguchi T, Iba H, Tsutsui H, Sato S, Nakajima S, Iijima H, Kubo M, Kunisawa J, Kiyono H (2012) Extracellular ATP mediates mast cell-dependent intestinal inflammation through P2X7 purinoceptors. Nat Commun 3:1034
Kurashima Y, Amiya T, Fujisawa K, Shibata N, Suzuki Y, Kogure Y, Hashimoto E, Otsuka A, Kabashima K, Sato S, Sato T, Kubo M, Akira S, Miyake K, Kunisawa J, Kiyono H (2014) The enzyme Cyp26b1 mediates inhibition of mast cell activation by fibroblasts to maintain skin-barrier homeostasis. Immunity 40(4):530–541
Lammas DA, Stober C, Harvey CJ, Kendrick N, Panchalingam S, Kumararatne DS (1997) ATP-induced killing of mycobacteria by human macrophages is mediated by purinergic P2Z(P2X7) receptors. Immunity 7(3):433–444
Lee HY, Bardini M, Burnstock G (2000) Distribution of P2X receptors in the urinary bladder and the ureter of the rat. J Urol 163(6):2002–2007
Lenertz LY, Wang Z, Guadarrama A, Hill LM, Gavala ML, Bertics PJ (2010) Mutation of putative N-linked glycosylation sites on the human nucleotide receptor P2X7 reveals a key residue important for receptor function. Biochemistry 49(22):4611–4619
Lenertz LY, Gavala ML, Zhu Y, Bertics PJ (2011) Transcriptional control mechanisms associated with the nucleotide receptor P2X7, a critical regulator of immunologic, osteogenic, and neurologic functions. Immunol Res 50(1):22–38
Li S, Tomic M, Stojilkovic SS (2011) Characterization of novel Pannexin 1 isoforms from rat pituitary cells and their association with ATP-gated P2X channels. Gen Comp Endocrinol 174(2):202–210
Li M, Silberberg SD, Swartz KJ (2013) Subtype-specific control of P2X receptor channel signaling by ATP and Mg2+. Proc Natl Acad Sci U S A 110(36):E3455–E3463
Li S, Li X, Coddou C, Geng X, Wei J, Sun J (2014) Molecular characterization and expression analysis of ATP-gated P2X7 receptor involved in Japanese flounder (Paralichthys olivaceus) innate immune response. PLoS One 9(5):e96625
Li G, Zou L, Xie W, Wen S, Xie Q, Gao Y, Xu C, Xu H, Liu S, Wang S, Xue Y, Wu B, Lv Q, Ying M, Zhang X, Liang S (2016) The effects of NONRATT021972 lncRNA siRNA on PC12 neuronal injury mediated by P2X7 receptor after exposure to oxygen-glucose deprivation. Purinergic Signal 12(3):479–487
Liang L, Schwiebert EM (2005) Large pore formation uniquely associated with P2X7 purinergic receptor channels. Focus on “Are second messengers crucial for opening the pore associated with P2X7 receptor?”. Am J Physiol Cell Physiol 288(2):C240–C242
Liang X, Samways DS, Wolf K, Bowles EA, Richards JP, Bruno J, Dutertre S, DiPaolo RJ, Egan TM (2015) Quantifying Ca2+ current and permeability in ATP-gated P2X7 receptors. J Biol Chem 290(12):7930–7942
Lin C, Ren S, Zhang L, Jin H, Sun J, Zuo Y (2012) Extracellular ATP induces CD44 shedding from macrophage-like P388D1 cells via the P2X7 receptor. Hematol Oncol 30(2):70–75
Liu X, Surprenant A, Mao HJ, Roger S, Xia R, Bradley H, Jiang LH (2008) Identification of key residues coordinating functional inhibition of P2X7 receptors by zinc and copper. Mol Pharmacol 73(1):252–259
Liu X, Ma W, Surprenant A, Jiang LH (2009) Identification of the amino acid residues in the extracellular domain of rat P2X7 receptor involved in functional inhibition by acidic pH. Br J Pharmacol 156(1):135–142
Liu Y, Xiao Y, Li Z (2011) P2X7 receptor positively regulates MyD88-dependent NF-kappaB activation. Cytokine 55(2):229–236
Liu S, Zou L, Xie J, Xie W, Wen S, Xie Q, Gao Y, Li G, Zhang C, Xu C, Xu H, Wu B, Lv Q, Zhang X, Wang S, Xue Y, Liang S (2016) LncRNA NONRATT021972 siRNA regulates neuropathic pain behaviors in type 2 diabetic rats through the P2X7 receptor in dorsal root ganglia. Mol Brain 9:44
Locovei S, Scemes E, Qiu F, Spray DC, Dahl G (2007) Pannexin1 is part of the pore forming unit of the P2X7 receptor death complex. FEBS Lett 581(3):483–488
Lopez-Castejon G, Young MT, Meseguer J, Surprenant A, Mulero V (2007) Characterization of ATP-gated P2X7 receptors in fish provides new insights into the mechanism of release of the leaderless cytokine interleukin-1 beta. Mol Immunol 44(6):1286–1299
Lopez-Castejon G, Theaker J, Pelegrin P, Clifton AD, Braddock M, Surprenant A (2010) P2X7 receptor-mediated release of cathepsins from macrophages is a cytokine-independent mechanism potentially involved in joint diseases. J Immunol 185(4):2611–2619
Lorden G, Sanjuan-Garcia I, de Pablo N, Meana C, Alvarez-Miguel I, Perez-Garcia MT, Pelegrin P, Balsinde J, Balboa MA (2017) Lipin-2 regulates NLRP3 inflammasome by affecting P2X7 receptor activation. J Exp Med 214(2):511–528
Lovelace MD, Gu BJ, Eamegdool SS, Weible MW 2nd, Wiley JS, Allen DG, Chan-Ling T (2015) P2X7 receptors mediate innate phagocytosis by human neural precursor cells and neuroblasts. Stem Cells 33(2):526–541
Mansoor SE, Lu W, Oosterheert W, Shekhar M, Tajkhorshid E, Gouaux E (2016) X-ray structures define human P2X3 receptor gating cycle and antagonist action. Nature 538(7623):66–71
Masin M, Young C, Lim K, Barnes SJ, Xu XJ, Marschall V, Brutkowski W, Mooney ER, Gorecki DC, Murrell-Lagnado R (2012) Expression, assembly and function of novel C-terminal truncated variants of the mouse P2X7 receptor: re-evaluation of P2X7 knockouts. Br J Pharmacol 165(4):978–993
Matute C (2011) Glutamate and ATP signalling in white matter pathology. J Anat 219(1):53–64
Mazzanti M, Innocenti B, Rigatelli M (1994) ATP-dependent ionic permeability on nuclear envelope in in situ nuclei of Xenopus oocytes. FASEB J 8(2):231–236
Mehta VB, Hart J, Wewers MD (2001) ATP-stimulated release of interleukin (IL)-1beta and IL-18 requires priming by lipopolysaccharide and is independent of caspase-1 cleavage. J Biol Chem 276(6):3820–3826
Menzies J, Paul A, Kennedy C (2003) P2X7 subunit-like immunoreactivity in the nucleus of visceral smooth muscle cells of the guinea pig. Auton Neurosci 106(2):103–109
Metzger MW, Walser SM, Aprile-Garcia F, Dedic N, Chen A, Holsboer F, Arzt E, Wurst W, Deussing JM (2017) Genetically dissecting P2rx7 expression within the central nervous system using conditional humanized mice. Purinergic Signal 13(2):153–170
Michel AD, Clay WC, Ng SW, Roman S, Thompson K, Condreay JP, Hall M, Holbrook J, Livermore D, Senger S (2008a) Identification of regions of the P2X7 receptor that contribute to human and rat species differences in antagonist effects. Br J Pharmacol 155(5):738–751
Michel AD, Chambers LJ, Walter DS (2008b) Negative and positive allosteric modulators of the P2X7 receptor. Br J Pharmacol 153(4):737–750
Michel AD, Ng SW, Roman S, Clay WC, Dean DK, Walter DS (2009) Mechanism of action of species-selective P2X7 receptor antagonists. Br J Pharmacol 156(8):1312–1325
Migita K, Ozaki T, Shimoyama S, Yamada J, Nikaido Y, Furukawa T, Shiba Y, Egan TM, Ueno S (2016) HSP90 regulation of P2X7 receptor function requires an intact cytoplasmic C-terminus. Mol Pharmacol 90(2):116–126
Miller CM, Boulter NR, Fuller SJ, Zakrzewski AM, Lees MP, Saunders BM, Wiley JS, Smith NC (2011) The role of the P2X7 receptor in infectious diseases. PLoS Pathog 7(11):e1002212
Minkiewicz J, de Rivero Vaccari JP, Keane RW (2013) Human astrocytes express a novel NLRP2 inflammasome. Glia 61(7):1113–1121
Moore SF, MacKenzie AB (2007) Murine macrophage P2X7 receptors support rapid prothrombotic responses. Cell Signal 19(4):855–866
Moura G, Lucena SV, Lima MA, Nascimento FD, Gesteira TF, Nader HB, Paredes-Gamero EJ, Tersariol I (2015a) Post-translational allosteric activation of the P2X7 receptor through glycosaminoglycan chains of CD44 proteoglycans. Cell Death Dis 1:15005
Moura GE, Lucena SV, Lima MA, Nascimento FD, Gesteira TF, Nader HB, Paredes-Gamero EJ, Tersariol IL (2015b) P2X7 receptor activity regulation: the role of CD44 proteoglycan GAG chains. Cell Death Dis 6:e1997
Nicke A (2008) Homotrimeric complexes are the dominant assembly state of native P2X7 subunits. Biochem Biophys Res Commun 377(3):803–808
Nicke A, Kuan YH, Masin M, Rettinger J, Marquez-Klaka B, Bender O, Gorecki DC, Murrell-Lagnado RD, Soto F (2009) A functional P2X7 splice variant with an alternative transmembrane domain 1 escapes gene inactivation in P2X7 knock-out mice. J Biol Chem 284(38):25813–25822
Norenberg W, Hempel C, Urban N, Sobottka H, Illes P, Schaefer M (2011) Clemastine potentiates the human P2X7 receptor by sensitizing it to lower ATP concentrations. J Biol Chem 286(13):11067–11081
Norenberg W, Sobottka H, Hempel C, Plotz T, Fischer W, Schmalzing G, Schaefer M (2012) Positive allosteric modulation by ivermectin of human but not murine P2X7 receptors. Br J Pharmacol 167(1):48–66
Norris PC, Gosselin D, Reichart D, Glass CK, Dennis EA (2014) Phospholipase A2 regulates eicosanoid class switching during inflammasome activation. Proc Natl Acad Sci U S A 111(35):12746–12751
North RA (2016) P2X receptors. Philos Trans R Soc Lond Ser B Biol Sci 371(1700):20150427
Novak I, Jans IM, Wohlfahrt L (2010) Effect of P2X7 receptor knockout on exocrine secretion of pancreas, salivary glands and lacrimal glands. J Physiol 588(Pt 18):3615–3627
Orellano EA, Rivera OJ, Chevres M, Chorna NE, Gonzalez FA (2010) Inhibition of neuronal cell death after retinoic acid-induced down-regulation of P2X7 nucleotide receptor expression. Mol Cell Biochem 337(1–2):83–99
Ousingsawat J, Wanitchakool P, Kmit A, Romao AM, Jantarajit W, Schreiber R, Kunzelmann K (2015) Anoctamin 6 mediates effects essential for innate immunity downstream of P2X7 receptors in macrophages. Nat Commun 6:6245
Park JH, Kim YC (2017) P2X7 receptor antagonists: a patent review (2010–2015). Expert Opin Ther Pat 27(3):257–267
Parker JC, Snow RL (1972) Influence of external ATP on permeability and metabolism of dog red blood cells. Am J Phys 223(4):888–893
Paukert M, Hidayat S, Grunder S (2002) The P2X7 receptor from Xenopus laevis: formation of a large pore in Xenopus oocytes. FEBS Lett 513(2–3):253–258
Pelegrin P, Surprenant A (2006) Pannexin-1 mediates large pore formation and interleukin-1beta release by the ATP-gated P2X7 receptor. EMBO J 25(21):5071–5082
Pelegrin P, Surprenant A (2007) Pannexin-1 couples to maitotoxin- and nigericin-induced interleukin-1beta release through a dye uptake-independent pathway. J Biol Chem 282(4):2386–2394
Peng W, Cotrina ML, Han X, Yu H, Bekar L, Blum L, Takano T, Tian GF, Goldman SA, Nedergaard M (2009) Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury. Proc Natl Acad Sci U S A 106(30):12489–12493
Pereira VS, Casarotto PC, Hiroaki-Sato VA, Sartim AG, Guimaraes FS, Joca SR (2013) Antidepressant- and anticompulsive-like effects of purinergic receptor blockade: involvement of nitric oxide. Eur Neuropsychopharmacol 23(12):1769–1778
Perez-Flores G, Levesque SA, Pacheco J, Vaca L, Lacroix S, Perez-Cornejo P, Arreola J (2015) The P2X7/P2X4 interaction shapes the purinergic response in murine macrophages. Biochem Biophys Res Commun 467(3):484–490
Perruzza L, Gargari G, Proietti M, Fosso B, D’Erchia AM, Faliti CE, Rezzonico-Jost T, Scribano D, Mauri L, Colombo D, Pellegrini G, Moregola A, Mooser C, Pesole G, Nicoletti M, Norata GD, Geuking MB, McCoy KD, Guglielmetti S, Grassi F (2017) T follicular helper cells promote a beneficial gut ecosystem for host metabolic homeostasis by sensing microbiota-derived extracellular ATP. Cell Rep 18(11):2566–2575
Pfleger C, Ebeling G, Blasche R, Patton M, Patel HH, Kasper M, Barth K (2012) Detection of caveolin-3/caveolin-1/P2X7R complexes in mice atrial cardiomyocytes in vivo and in vitro. Histochem Cell Biol 138(2):231–241
Pochet S, Tandel S, Querriere S, Tre-Hardy M, Garcia-Marcos M, De Lorenzi M, Vandenbranden M, Marino A, Devleeschouwer M, Dehaye JP (2006) Modulation by LL-37 of the responses of salivary glands to purinergic agonists. Mol Pharmacol 69(6):2037–2046
Poornima V, Madhupriya M, Kootar S, Sujatha G, Kumar A, Bera AK (2012) P2X7 receptor-pannexin 1 hemichannel association: effect of extracellular calcium on membrane permeabilization. J Mol Neurosci 46(3):585–594
Pupovac A, Sluyter R (2016) Roles of extracellular nucleotides and P2 receptors in ectodomain shedding. Cell Mol Life Sci 73(22):4159–4173
Pupovac A, Geraghty NJ, Watson D, Sluyter R (2015) Activation of the P2X7 receptor induces the rapid shedding of CD23 from human and murine B cells. Immunol Cell Biol 93(1):77–85
Qiu F, Dahl G (2009) A permeant regulating its permeation pore: inhibition of pannexin 1 channels by ATP. Am J Physiol Cell Physiol 296(2):C250–C255
Qu Y, Misaghi S, Newton K, Gilmour LL, Louie S, Cupp JE, Dubyak GR, Hackos D, Dixit VM (2011) Pannexin-1 is required for ATP release during apoptosis but not for inflammasome activation. J Immunol 186(11):6553–6561
Rahman OA, Sasvari-Szekely M, Szekely A, Faludi G, Guttman A, Nemoda Z (2010) Analysis of a polymorphic microRNA target site in the purinergic receptor P2RX7 gene. Electrophoresis 31(11):1790–1795
Rassendren F, Buell GN, Virginio C, Collo G, North RA, Surprenant A (1997) The permeabilizing ATP receptor, P2X7. Cloning and expression of a human cDNA. J Biol Chem 272(9):5482–5486
Rissiek B, Haag F, Boyer O, Koch-Nolte F, Adriouch S (2015) P2X7 on mouse T cells: one channel, many functions. Front Immunol 6:204
Robinson LE, Shridar M, Smith P, Murrell-Lagnado RD (2014) Plasma membrane cholesterol as a regulator of human and rodent P2X7 receptor activation and sensitization. J Biol Chem 289(46):31983–31994
Roger S, Pelegrin P, Surprenant A (2008) Facilitation of P2X7 receptor currents and membrane blebbing via constitutive and dynamic calmodulin binding. J Neurosci 28(25):6393–6401
Roger S, Mei ZZ, Baldwin JM, Dong L, Bradley H, Baldwin SA, Surprenant A, Jiang LH (2010a) Single nucleotide polymorphisms that were identified in affective mood disorders affect ATP-activated P2X7 receptor functions. J Psychiatr Res 44(6):347–355
Roger S, Gillet L, Baroja-Mazo A, Surprenant A, Pelegrin P (2010b) C-terminal calmodulin-binding motif differentially controls human and rat P2X7 receptor current facilitation. J Biol Chem 285(23):17514–17524
Roger S, Jelassi B, Couillin I, Pelegrin P, Besson P, Jiang LH (2015) Understanding the roles of the P2X7 receptor in solid tumour progression and therapeutic perspectives. Biochim Biophys Acta 1848(10 Pt B):2584–2602
Roman S, Cusdin FS, Fonfria E, Goodwin JA, Reeves J, Lappin SC, Chambers L, Walter DS, Clay WC, Michel AD (2009) Cloning and pharmacological characterization of the dog P2X7 receptor. Br J Pharmacol 158(6):1513–1526
Rorive G, Kleinzeller A (1972) The effect of ATP and Ca 2+ on the cell volume in isolated kidney tubules. Biochim Biophys Acta 274(1):226–239
Rossi L, Salvestrini V, Ferrari D, Di Virgilio F, Lemoli RM (2012) The sixth sense: hematopoietic stem cells detect danger through purinergic signaling. Blood 120(12):2365–2375
Royle SJ, Bobanovic LK, Murrell-Lagnado RD (2002) Identification of a non-canonical tyrosine-based endocytic motif in an ionotropic receptor. J Biol Chem 277(38):35378–35385
Rozengurt E, Heppel LA (1975) A specific effect of external ATP on the permeability of transformed 3T3 cells. Biochem Biophys Res Commun 67(4):1581–1588
Sakaki H, Fujiwaki T, Tsukimoto M, Kawano A, Harada H, Kojima S (2013) P2X4 receptor regulates P2X7 receptor-dependent IL-1beta and IL-18 release in mouse bone marrow-derived dendritic cells. Biochem Biophys Res Commun 432(3):406–411
Sanchez-Nogueiro J, Marin-Garcia P, Bustillo D, Olivos-Ore LA, Miras-Portugal MT, Artalejo AR (2014) Subcellular distribution and early signalling events of P2X7 receptors from mouse cerebellar granule neurons. Eur J Pharmacol 744:190–202
Sanderson J, Dartt DA, Trinkaus-Randall V, Pintor J, Civan MM, Delamere NA, Fletcher EL, Salt TE, Grosche A, Mitchell CH (2014) Purines in the eye: recent evidence for the physiological and pathological role of purines in the RPE, retinal neurons, astrocytes, Muller cells, lens, trabecular meshwork, cornea and lacrimal gland. Exp Eye Res 127:270–279
Sandilos JK, Chiu YH, Chekeni FB, Armstrong AJ, Walk SF, Ravichandran KS, Bayliss DA (2012) Pannexin 1, an ATP release channel, is activated by caspase cleavage of its pore-associated C-terminal autoinhibitory region. J Biol Chem 287(14):11303–11311
Sanz JM, Chiozzi P, Di Virgilio F (1998) Tenidap enhances P2Z/P2X7 receptor signalling in macrophages. Eur J Pharmacol 355(2–3):235–244
Sathanoori R, Sward K, Olde B, Erlinge D (2015) The ATP receptors P2X7 and P2X4 modulate high glucose and palmitate-induced inflammatory responses in endothelial cells. PLoS One 10(5):e0125111
Schilling E, Hauschildt S (2012) Extracellular ATP induces P2X7-dependent nicotinamide phosphoribosyltransferase release in LPS-activated human monocytes. Innate Immun 18(5):738–744
Schwarz N, Drouot L, Nicke A, Fliegert R, Boyer O, Guse AH, Haag F, Adriouch S, Koch-Nolte F (2012) Alternative splicing of the N-terminal cytosolic and transmembrane domains of P2X7 controls gating of the ion channel by ADP-ribosylation. PLoS One 7(7):e41269
Seman M, Adriouch S, Scheuplein F, Krebs C, Freese D, Glowacki G, Deterre P, Haag F, Koch-Nolte F (2003) NAD-induced T cell death: ADP-ribosylation of cell surface proteins by ART2 activates the cytolytic P2X7 purinoceptor. Immunity 19(4):571–582
Seyffert C, Schmalzing G, Markwardt F (2004) Dissecting individual current components of co-expressed human P2X1 and P2X7 receptors. Curr Top Med Chem 4(16):1719–1730
Sha WG, Shen L, Zhou L, Xu DY, Lu GY (2015) Down-regulation of miR-186 contributes to podocytes apoptosis in membranous nephropathy. Biomed Pharmacother 75:179–184
Shiozaki Y, Sato M, Kimura M, Sato T, Tazaki M, Shibukawa Y (2017) Ionotropic P2X ATP receptor channels mediate purinergic signaling in mouse odontoblasts. Front Physiol 8:3
Shoji KF, Saez PJ, Harcha PA, Aguila HL, Saez JC (2014) Pannexin1 channels act downstream of P2X 7 receptors in ATP-induced murine T-cell death. Channels (Austin) 8(2):142–156
Shrivastava AN, Rodriguez PC, Triller A, Renner M (2013) Dynamic micro-organization of P2X7 receptors revealed by PALM based single particle tracking. Front Cell Neurosci 7:232
Silverman WR, de Rivero Vaccari JP, Locovei S, Qiu F, Carlsson SK, Scemes E, Keane RW, Dahl G (2009) The pannexin 1 channel activates the inflammasome in neurons and astrocytes. J Biol Chem 284(27):18143–18151
Skarratt KK, Fuller SJ, Sluyter R, Dao-Ung LP, Gu BJ, Wiley JS (2005) A 5′ intronic splice site polymorphism leads to a null allele of the P2X7 gene in 1-2% of the Caucasian population. FEBS Lett 579(12):2675–2678
Slater M, Danieletto S, Barden JA (2005) Expression of the apoptotic calcium channel P2X7 in the glandular epithelium. J Mol Histol 36(3):159–165
Sluyter R (2015) P2X and P2Y receptor signaling in red blood cells. Front Mol Biosci 2:60
Sluyter R, Stokes L (2011) Significance of P2X7 receptor variants to human health and disease. Recent Pat DNA Gene Seq 5(1):41–54
Sluyter R, Stokes L (2014) Polymorphic variants of the P2X7 receptor in the domestic dog. JJ Vet Sci Res 1(1):008
Sluyter R, Barden JA, Wiley JS (2001) Detection of P2X purinergic receptors on human B lymphocytes. Cell Tissue Res 304(2):231–236
Smart ML, Panchal RG, Bowser DN, Williams DA, Petrou S (2002) Pore formation is not associated with macroscopic redistribution of P2X7 receptors. Am J Physiol Cell Physiol 283(1):C77–C84
Smart ML, Gu B, Panchal RG, Wiley J, Cromer B, Williams DA, Petrou S (2003) P2X7 receptor cell surface expression and cytolytic pore formation are regulated by a distal C-terminal region. J Biol Chem 278(10):8853–8860
Solle M, Labasi J, Perregaux DG, Stam E, Petrushova N, Koller BH, Griffiths RJ, Gabel CA (2001) Altered cytokine production in mice lacking P2X7 receptors. J Biol Chem 276(1):125–132
Sommer A, Fries A, Cornelsen I, Speck N, Koch-Nolte F, Gimpl G, Andra J, Bhakdi S, Reiss K (2012) Melittin modulates keratinocyte function through P2 receptor-dependent ADAM activation. J Biol Chem 287(28):23678–23689
Sophocleous RA, Mullany PR, Winter KM, Marks DC, Sluyter R (2015) Propensity of red blood cells to undergo P2X7 receptor-mediated phosphatidylserine exposure does not alter during in vivo or ex vivo aging. Transfusion 55(8):1946–1954
Sorge RE, Trang T, Dorfman R, Smith SB, Beggs S, Ritchie J, Austin JS, Zaykin DV, Vander Meulen H, Costigan M, Herbert TA, Yarkoni-Abitbul M, Tichauer D, Livneh J, Gershon E, Zheng M, Tan K, John SL, Slade GD, Jordan J, Woolf CJ, Peltz G, Maixner W, Diatchenko L, Seltzer Z, Salter MW, Mogil JS (2012) Genetically determined P2X7 receptor pore formation regulates variability in chronic pain sensitivity. Nat Med 18(4):595–599
Sperlagh B, Illes P (2014) P2X7 receptor: an emerging target in central nervous system diseases. Trends Pharmacol Sci 35(10):537–547
Spildrejorde M, Bartlett R, Stokes L, Jalilian I, Peranec M, Sluyter V, Curtis BL, Skarratt KK, Skora A, Bakhsh T, Seavers A, McArthur JD, Dowton M, Sluyter R (2014) R270C polymorphism leads to loss of function of the canine P2X7 receptor. Physiol Genomics 46(14):512–522
Stock TC, Bloom BJ, Wei N, Ishaq S, Park W, Wang X, Gupta P, Mebus CA (2012) Efficacy and safety of CE-224,535, an antagonist of P2X7 receptor, in treatment of patients with rheumatoid arthritis inadequately controlled by methotrexate. J Rheumatol 39(4):720–727
Stokes L, Jiang LH, Alcaraz L, Bent J, Bowers K, Fagura M, Furber M, Mortimore M, Lawson M, Theaker J, Laurent C, Braddock M, Surprenant A (2006) Characterization of a selective and potent antagonist of human P2X7 receptors, AZ11645373. Br J Pharmacol 149(7):880–887
Stokes L, Fuller SJ, Sluyter R, Skarratt KK, Gu BJ, Wiley JS (2010) Two haplotypes of the P2X7 receptor containing the Ala-348 to Thr polymorphism exhibit a gain-of-function effect and enhanced interleukin-1beta secretion. FASEB J 24(8):2916–2927
Stokes L, Spencer SJ, Jenkins TA (2015) Understanding the role of P2X7 in affective disorders-are glial cells the major players? Front Cell Neurosci 9:258
Stolz M, Klapperstuck M, Kendzierski T, Detro-Dassen S, Panning A, Schmalzing G, Markwardt F (2015) Homodimeric anoctamin-1, but not homodimeric anoctamin-6, is activated by calcium increases mediated by the P2Y1 and P2X7 receptors. Pflugers Arch 467(10):2121–2140
Sun C, Chu J, Singh S, Salter RD (2010) Identification and characterization of a novel variant of the human P2X7 receptor resulting in gain of function. Purinergic Signal 6(1):31–45
Surprenant A, Rassendren F, Kawashima E, North RA, Buell G (1996) The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7). Science 272(5262):735–738
Syberg S, Schwarz P, Petersen S, Steinberg TH, Jensen JE, Teilmann J, Jorgensen NR (2012a) Association between P2X7 receptor polymorphisms and bone status in mice. J Osteoporos 2012:637986
Syberg S, Petersen S, Beck Jensen JE, Gartland A, Teilmann J, Chessell I, Steinberg TH, Schwarz P, Jorgensen NR (2012b) Genetic background strongly influences the bone phenotype of P2X7 receptor knockout mice. J Osteoporos 2012:391097
Tang Y, Wang Y, Park KM, Hu Q, Teoh JP, Broskova Z, Ranganathan P, Jayakumar C, Li J, Su H, Tang Y, Ramesh G, Kim IM (2015) MicroRNA-150 protects the mouse heart from ischaemic injury by regulating cell death. Cardiovasc Res 106(3):387–397
Taylor SR, Gonzalez-Begne M, Sojka DK, Richardson JC, Sheardown SA, Harrison SM, Pusey CD, Tam FW, Elliott JI (2009) Lymphocytes from P2X7-deficient mice exhibit enhanced P2X7 responses. J Leukoc Biol 85(6):978–986
Tewari M, Seth P (2015) Emerging role of P2X7 receptors in CNS health and disease. Ageing Res Rev 24(Pt B):328–342
Todd JN, Poon W, Lyssenko V, Groop L, Nichols B, Wilmot M, Robson S, Enjyoji K, Herman MA, Hu C, Zhang R, Jia W, Ma R, Florez JC, Friedman DJ (2015) Variation in glucose homeostasis traits associated with P2RX7 polymorphisms in mice and humans. J Clin Endocrinol Metab 100(5):E688–E696
Tomasinsig L, Pizzirani C, Skerlavaj B, Pellegatti P, Gulinelli S, Tossi A, Di Virgilio F, Zanetti M (2008) The human cathelicidin LL-37 modulates the activities of the P2X7 receptor in a structure-dependent manner. J Biol Chem 283(45):30471–30481
Torres GE, Egan TM, Voigt MM (1999) Hetero-oligomeric assembly of P2X receptor subunits. Specificities exist with regard to possible partners. J Biol Chem 274(10):6653–6659
Trams EG (1974) Evidence for ATP action on the cell surface. Nature 252(5483):480–482
Truve K, Dickinson P, Xiong A, York D, Jayashankar K, Pielberg G, Koltookian M, Muren E, Fuxelius HH, Weishaupt H, Swartling FJ (2016) Utilizing the dog genome in the search for novel candidate genes involved in glioma development-genome wide association mapping followed by targeted massive parallel sequencing identifies a strongly associated locus. PLoS Genet 12(5):e1006000
Tu G, Zou L, Liu S, Wu B, Lv Q, Wang S, Xue Y, Zhang C, Yi Z, Zhang X, Li G, Liang S (2016) Long noncoding NONRATT021972 siRNA normalized abnormal sympathetic activity mediated by the upregulation of P2X7 receptor in superior cervical ganglia after myocardial ischemia. Purinergic Signal 12(3):521–535
Virginio C, MacKenzie A, Rassendren FA, North RA, Surprenant A (1999) Pore dilation of neuronal P2X receptor channels. Nat Neurosci 2(4):315–321
Wang X, Arcuino G, Takano T, Lin J, Peng WG, Wan P, Li P, Xu Q, Liu QS, Goldman SA, Nedergaard M (2004) P2X7 receptor inhibition improves recovery after spinal cord injury. Nat Med 10(8):821–827
Wang J, Huo K, Ma L, Tang L, Li D, Huang X, Yuan Y, Li C, Wang W, Guan W, Chen H, Jin C, Wei J, Zhang W, Yang Y, Liu Q, Zhou Y, Zhang C, Wu Z, Xu W, Zhang Y, Liu T, Yu D, Zhang Y, Chen L, Zhu D, Zhong X, Kang L, Gan X, Yu X, Ma Q, Yan J, Zhou L, Liu Z, Zhu Y, Zhou T, He F, Yang X (2011) Toward an understanding of the protein interaction network of the human liver. Mol Syst Biol 7:536
Wei L, Caseley E, Li D, Jiang LH (2016) ATP-induced P2X receptor-dependent large pore formation: how much do we know? Front Pharmacol 7:5
Weinhold K, Krause-Buchholz U, Rodel G, Kasper M, Barth K (2010) Interaction and interrelation of P2X7 and P2X4 receptor complexes in mouse lung epithelial cells. Cell Mol Life Sci 67(15):2631–2642
Weng T, Mishra A, Guo Y, Wang Y, Su L, Huang C, Zhao C, Xiao X, Liu L (2012) Regulation of lung surfactant secretion by microRNA-150. Biochem Biophys Res Commun 422(4):586–589
Wesselius A, Bours MJ, Henriksen Z, Syberg S, Petersen S, Schwarz P, Jorgensen NR, van Helden S, Dagnelie PC (2013) Association of P2X7 receptor polymorphisms with bone mineral density and osteoporosis risk in a cohort of Dutch fracture patients. Osteoporos Int 24(4):1235–1246
Wickert LE, Blanchette JB, Waldschmidt NV, Bertics PJ, Denu JM, Denlinger LC, Lenertz LY (2013) The C-terminus of human nucleotide receptor P2X7 is critical for receptor oligomerization and N-linked glycosylation. PLoS One 8(5):e63789
Wiley JS, Dubyak GR (1989) Extracellular adenosine triphosphate increases cation permeability of chronic lymphocytic leukemic lymphocytes. Blood 73(5):1316–1323
Wiley JS, Gu BJ (2012) A new role for the P2X7 receptor: a scavenger receptor for bacteria and apoptotic cells in the absence of serum and extracellular ATP. Purinergic Signal 8(3):579–586
Wiley JS, Chen R, Wiley MJ, Jamieson GP (1992) The ATP4- receptor-operated ion channel of human lymphocytes: inhibition of ion fluxes by amiloride analogs and by extracellular sodium ions. Arch Biochem Biophys 292(2):411–418
Wiley JS, Gargett CE, Zhang W, Snook MB, Jamieson GP (1998) Partial agonists and antagonists reveal a second permeability state of human lymphocyte P2Z/P2X7 channel. Am J Phys 275(5 Pt 1):C1224–C1231
Wiley JS, Dao-Ung LP, Li C, Shemon AN, Gu BJ, Smart ML, Fuller SJ, Barden JA, Petrou S, Sluyter R (2003) An Ile-568 to Asn polymorphism prevents normal trafficking and function of the human P2X7 receptor. J Biol Chem 278(19):17108–17113
Wilson HL, Wilson SA, Surprenant A, North RA (2002) Epithelial membrane proteins induce membrane blebbing and interact with the P2X7 receptor C terminus. J Biol Chem 277(37):34017–34023
Woods LT, Camden JM, Batek JM, Petris MJ, Erb L, Weisman GA (2012) P2X7 receptor activation induces inflammatory responses in salivary gland epithelium. Am J Physiol Cell Physiol 303(7):C790–C801
Wu C, Ma MH, Brown KR, Geisler M, Li L, Tzeng E, Jia CY, Jurisica I, Li SS (2007) Systematic identification of SH3 domain-mediated human protein-protein interactions by peptide array target screening. Proteomics 7(11):1775–1785
Wu PY, Lin YC, Chang CL, Lu HT, Chin CH, Hsu TT, Chu D, Sun SH (2009) Functional decreases in P2X7 receptors are associated with retinoic acid-induced neuronal differentiation of Neuro-2a neuroblastoma cells. Cell Signal 21(6):881–891
Wu B, Zhang C, Zou L, Ma Y, Huang K, Lv Q, Zhang X, Wang S, Xue Y, Yi Z, Jia T, Zhao S, Liu S, Xu H, Li G, Liang S (2016) LncRNA uc.48+ siRNA improved diabetic sympathetic neuropathy in type 2 diabetic rats mediated by P2X7 receptor in SCG. Auton Neurosci 197:14–18
Xu XJ, Boumechache M, Robinson LE, Marschall V, Gorecki DC, Masin M, Murrell-Lagnado RD (2012) Splice variants of the P2X7 receptor reveal differential agonist dependence and functional coupling with pannexin-1. J Cell Sci 125(Pt 16):3776–3789
Xu H, He L, Liu C, Tang L, Xu Y, Xiong M, Yang M, Fan Y, Hu F, Liu X, Ding L, Gao Y, Xu C, Li G, Liu S, Wu B, Zou L, Liang S (2016) LncRNA NONRATT021972 siRNA attenuates P2X7 receptor expression and inflammatory cytokine production induced by combined high glucose and free fatty acids in PC12 cells. Purinergic Signal 12(2):259–268
Yamamoto M, Kamatsuka Y, Ohishi A, Nishida K, Nagasawa K (2013) P2X7 receptors regulate engulfing activity of non-stimulated resting astrocytes. Biochem Biophys Res Commun 439(1):90–95
Yan Z, Li S, Liang Z, Tomic M, Stojilkovic SS (2008) The P2X7 receptor channel pore dilates under physiological ion conditions. J Gen Physiol 132(5):563–573
Yang D, He Y, Munoz-Planillo R, Liu Q, Nunez G (2015) Caspase-11 Requires the Pannexin-1 Channel and the Purinergic P2X7 Pore to Mediate Pyroptosis and Endotoxic Shock. Immunity 43(5):923–932
Young MT, Pelegrin P, Surprenant A (2006) Identification of Thr283 as a key determinant of P2X7 receptor function. Br J Pharmacol 149(3):261–268
Young MT, Pelegrin P, Surprenant A (2007) Amino acid residues in the P2X7 receptor that mediate differential sensitivity to ATP and BzATP. Mol Pharmacol 71(1):92–100
Young CN, Brutkowski W, Lien CF, Arkle S, Lochmuller H, Zablocki K, Gorecki DC (2012) P2X7 purinoceptor alterations in dystrophic mdx mouse muscles: relationship to pathology and potential target for treatment. J Cell Mol Med 16(5):1026–1037
Young CN, Sinadinos A, Lefebvre A, Chan P, Arkle S, Vaudry D, Gorecki DC (2015) A novel mechanism of autophagic cell death in dystrophic muscle regulated by P2RX7 receptor large-pore formation and HSP90. Autophagy 11(1):113–130
Zheng L, Zhang X, Yang F, Zhu J, Zhou P, Yu F, Hou L, Xiao L, He Q, Wang B (2014) Regulation of the P2X7R by microRNA-216b in human breast cancer. Biochem Biophys Res Commun 452(1):197–204
Zhou L, Qi X, Potashkin JA, Abdul-Karim FW, Gorodeski GI (2008) MicroRNAs miR-186 and miR-150 down-regulate expression of the pro-apoptotic purinergic P2X7 receptor by activation of instability sites at the 3′-untranslated region of the gene that decrease steady-state levels of the transcript. J Biol Chem 283(42):28274–28286
Zhou L, Luo L, Qi X, Li X, Gorodeski GI (2009) Regulation of P2X7 gene transcription. Purinergic Signal 5(3):409–426
Zou L, Tu G, Xie W, Wen S, Xie Q, Liu S, Li G, Gao Y, Xu H, Wang S, Xue Y, Wu B, Lv Q, Ying M, Zhang X, Liang S (2016) LncRNA NONRATT021972 involved the pathophysiologic processes mediated by P2X7 receptors in stellate ganglia after myocardial ischemic injury. Purinergic Signal 12(1):127–137
Compliance with Ethical Standards
Conflicts of Interest
The author declares that he has no conflicts of interest.
Ethical Approval
This article does not contain any studies with human participants or animals performed by the author.
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Sluyter, R. (2017). The P2X7 Receptor. In: Atassi, M. (eds) Protein Reviews. Advances in Experimental Medicine and Biology(), vol 1051. Springer, Singapore. https://doi.org/10.1007/5584_2017_59
Download citation
DOI: https://doi.org/10.1007/5584_2017_59
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-10-7610-7
Online ISBN: 978-981-10-7611-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)