P2RX7

{{Short description|Protein-coding gene in the species Homo sapiens}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Infobox_gene}} {{Purinergic signalling}} '''P2X purinoceptor 7''' is a protein that in humans is encoded by the ''P2RX7'' gene.<ref name="Rassendren_1997">{{cite journal | vauthors = Rassendren F, Buell GN, Virginio C, Collo G, North RA, Surprenant A | title = The permeabilizing ATP receptor, P2X7. Cloning and expression of a human cDNA | journal = The Journal of Biological Chemistry | volume = 272 | issue = 9 | pages = 5482–5486 | date = February 1997 | pmid = 9038151 | doi = 10.1074/jbc.272.9.5482 | doi-access = free }}</ref><ref name="Buell_1999">{{cite journal | vauthors = Buell GN, Talabot F, Gos A, Lorenz J, Lai E, Morris MA, Antonarakis SE | title = Gene structure and chromosomal localization of the human P2X7 receptor | journal = Receptors & Channels | volume = 5 | issue = 6 | pages = 347–354 | date = Feb 1999 | pmid = 9826911 }}</ref>

The product of this gene belongs to the family of purinoceptors for ATP. Multiple alternatively spliced variants which would encode different isoforms have been identified although some fit nonsense-mediated decay criteria.<ref>{{cite web | title = Entrez Gene: P2RX7 purinergic receptor P2X, ligand-gated ion channel, 7 | url = https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=5027 }}</ref>

The receptor is found in the central and peripheral nervous systems, in microglia, in macrophages, in uterine endometrium, and in the retina.<ref name="Faria_2017">{{cite journal | vauthors = Faria RX, Freitas HR, Reis RA | title = P2X7 receptor large pore signaling in avian Müller glial cells | journal = Journal of Bioenergetics and Biomembranes | volume = 49 | issue = 3 | pages = 215–229 | date = June 2017 | pmid = 28573491 | doi = 10.1007/s10863-017-9717-9 | s2cid = 4122579 }}</ref><ref name="Freitas_2017" /><ref name="Freitas_2016" /><ref name="Deuchars_2001">{{cite journal | vauthors = Deuchars SA, Atkinson L, Brooke RE, Musa H, Milligan CJ, Batten TF, Buckley NJ, Parson SH, Deuchars J | title = Neuronal P2X7 receptors are targeted to presynaptic terminals in the central and peripheral nervous systems | journal = The Journal of Neuroscience | volume = 21 | issue = 18 | pages = 7143–7152 | date = September 2001 | pmid = 11549725 | pmc = 6762981 | doi = 10.1523/JNEUROSCI.21-18-07143.2001 }}</ref><ref name="Collo_1997">{{cite journal | vauthors = Collo G, Neidhart S, Kawashima E, Kosco-Vilbois M, North RA, Buell G | title = Tissue distribution of the P2X7 receptor | journal = Neuropharmacology | volume = 36 | issue = 9 | pages = 1277–1283 | date = September 1997 | pmid = 9364482 | doi = 10.1016/S0028-3908(97)00140-8 | s2cid = 21491471 }}</ref><ref name="Slater_2000">{{cite journal | vauthors = Slater NM, Barden JA, Murphy CR | title = Distributional changes of purinergic receptor subtypes (P2X 1-7) in uterine epithelial cells during early pregnancy | journal = The Histochemical Journal | volume = 32 | issue = 6 | pages = 365–372 | date = June 2000 | pmid = 10943851 | doi = 10.1023/A:1004017714702 | s2cid = 40282870 }}</ref><ref name="Ishii_2003">{{cite journal | vauthors = Ishii K, Kaneda M, Li H, Rockland KS, Hashikawa T | title = Neuron-specific distribution of P2X7 purinergic receptors in the monkey retina | journal = The Journal of Comparative Neurology | volume = 459 | issue = 3 | pages = 267–277 | date = May 2003 | pmid = 12655509 | doi = 10.1002/cne.10608 | s2cid = 9692745 }}</ref> The P2X7 receptor also serves as a pattern recognition receptor for extracellular ATP-mediated apoptotic cell death,<ref>{{cite journal | vauthors = Freitas HR, Reis RA, Ventura AL, França GR | title = Interaction between cannabinoid and nucleotide systems as a new mechanism of signaling in retinal cell death | journal = Neural Regeneration Research | volume = 14 | issue = 12 | pages = 2093–2094 | date = December 2019 | pmid = 31397346 | pmc = 6788250 | doi = 10.4103/1673-5374.262585 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Freitas HR, Isaac AR, Silva TM, Diniz GO, Dos Santos Dabdab Y, Bockmann EC, Guimarães MZ, da Costa Calaza K, de Mello FG, Ventura AL, de Melo Reis RA, França GR | title = Cannabinoids Induce Cell Death and Promote P2X7 Receptor Signaling in Retinal Glial Progenitors in Culture | journal = Molecular Neurobiology | volume = 56 | issue = 9 | pages = 6472–6486 | date = September 2019 | pmid = 30838518 | doi = 10.1007/s12035-019-1537-y | s2cid = 71143662 }}</ref><ref name="Kawano_2012">{{cite journal | vauthors = Kawano A, Tsukimoto M, Noguchi T, Hotta N, Harada H, Takenouchi T, Kitani H, Kojima S | title = Involvement of P2X4 receptor in P2X7 receptor-dependent cell death of mouse macrophages | journal = Biochemical and Biophysical Research Communications | volume = 419 | issue = 2 | pages = 374–380 | date = March 2012 | pmid = 22349510 | doi = 10.1016/j.bbrc.2012.01.156 | bibcode = 2012BBRC..419..374K }}</ref> regulation of receptor trafficking,<ref name="Qu_2009">{{cite journal | vauthors = Qu Y, Dubyak GR | title = P2X7 receptors regulate multiple types of membrane trafficking responses and non-classical secretion pathways | journal = Purinergic Signalling | volume = 5 | issue = 2 | pages = 163–173 | date = June 2009 | pmid = 19189228 | pmc = 2686822 | doi = 10.1007/s11302-009-9132-8 }}</ref> mast cell degranulation,<ref name="P2x7 gastrointestinal MC review" /><ref name="Wareham_2016">{{cite journal | vauthors = Wareham KJ, Seward EP | title = P2X7 receptors induce degranulation in human mast cells | journal = Purinergic Signalling | volume = 12 | issue = 2 | pages = 235–246 | date = June 2016 | pmid = 26910735 | pmc = 4854833 | doi = 10.1007/s11302-016-9497-4 }}</ref> and inflammation.<ref>{{cite journal | vauthors = Gonzaga DT, Ferreira LB, Moreira Maramaldo Costa TE, von Ranke NL, Anastácio Furtado Pacheco P, Sposito Simões AP, Arruda JC, Dantas LP, de Freitas HR, de Melo Reis RA, Penido C, Bello ML, Castro HC, Rodrigues CR, Ferreira VF, Faria RX, da Silva FC | title = 1-Aryl-1H- and 2-aryl-2H-1,2,3-triazole derivatives blockade P2X7 receptor in vitro and inflammatory response in vivo | journal = European Journal of Medicinal Chemistry | volume = 139 | pages = 698–717 | date = October 2017 | pmid = 28858765 | doi = 10.1016/j.ejmech.2017.08.034 | url = http://www.sciencedirect.com/science/article/pii/S0223523417306372 | url-access = subscription }}</ref><ref name="P2x7 gastrointestinal MC review">{{cite journal | vauthors = Kurashima Y, Kiyono H | title = New era for mucosal mast cells: their roles in inflammation, allergic immune responses and adjuvant development | journal = Experimental & Molecular Medicine | volume = 46 | issue = 3 | pages = e83 | date = March 2014 | pmid = 24626169 | pmc = 3972796 | doi = 10.1038/emm.2014.7 }}</ref><ref name="Wareham_2016" /><ref name="DAMPs PAMPs and PRRs">{{cite journal | vauthors = Russo MV, McGavern DB | title = Immune Surveillance of the CNS following Infection and Injury | journal = Trends in Immunology | volume = 36 | issue = 10 | pages = 637–650 | date = October 2015 | pmid = 26431941 | pmc = 4592776 | doi = 10.1016/j.it.2015.08.002 }}</ref> Regarding inflammation, P2X7 receptor induces the NLRP3 inflammasome in myeloid cells and leads to interleukin-1beta release.<ref>{{cite journal | vauthors = Pelegrin P, Barroso-Gutierrez C, Surprenant A | title = P2X7 receptor differentially couples to distinct release pathways for IL-1beta in mouse macrophage | journal = Journal of Immunology | volume = 180 | issue = 11 | pages = 7147–7157 | date = June 2008 | pmid = 18490713 | doi = 10.4049/jimmunol.180.11.7147 }}</ref>

== Structure and kinetics ==

The P2X7 subunits can form homomeric receptors only with a typical P2X receptor structure.<ref name="Torres_1999">{{cite journal | vauthors = Torres GE, Egan TM, Voigt MM | title = Hetero-oligomeric assembly of P2X receptor subunits. Specificities exist with regard to possible partners | journal = The Journal of Biological Chemistry | volume = 274 | issue = 10 | pages = 6653–6659 | date = March 1999 | pmid = 10037762 | doi = 10.1074/jbc.274.10.6653 | doi-access = free }}</ref> The P2X7 receptor is a ligand-gated cation channel that opens in response to ATP binding and leads to cell depolarization. The P2X7 receptor requires higher levels of ATP than other P2X receptors; however, the response can be potentiated by reducing the concentration of divalent cations such as calcium or magnesium.<ref name="Faria_2017" /><ref name="North_2002" /> Continued binding leads to increased permeability to ''N''-methyl-D-glucamine (NMDG+).<ref name="North_2002">{{cite journal | vauthors = North RA | title = Molecular physiology of P2X receptors | journal = Physiological Reviews | volume = 82 | issue = 4 | pages = 1013–1067 | date = October 2002 | pmid = 12270951 | doi = 10.1152/physrev.00015.2002 }}</ref> P2X7 receptors do not become desensitized readily and continued signaling leads to the aforementioned increased permeability and an increase in current amplitude.<ref name="North_2002" />

== Pharmacology ==

=== Agonists === * P2X7 receptors respond to BzATP more readily than ATP.<ref name="North_2002" /> * ADP and AMP are weak agonists of P2X7 receptors, but a brief exposure to ATP can increase their effectiveness.<ref name="North_2002" /> * Glutathione has been proposed to act as a P2X7 receptor agonist when present at milimolar levels, inducing calcium transients and GABA release from retinal cells.<ref name="Freitas_2016">{{cite journal | vauthors = Freitas HR, Ferraz G, Ferreira GC, Ribeiro-Resende VT, Chiarini LB, do Nascimento JL, Matos Oliveira KR, de Lima Pereira T, Ferreira LG, Kubrusly RC, Faria RX, Herculano AM, Reis RA | title = Glutathione-Induced Calcium Shifts in Chick Retinal Glial Cells | journal = PLOS ONE | volume = 11 | issue = 4 | article-number = e0153677 | date = April 2016 | pmid = 27078878 | pmc = 4831842 | doi = 10.1371/journal.pone.0153677 | bibcode = 2016PLoSO..1153677F | doi-access = free }}</ref><ref name="Freitas_2017">{{cite journal | vauthors = Freitas HR, Reis RA | title = 7R activation on Müller glia | journal = Neurogenesis | volume = 4 | issue = 1 | article-number = e1283188 | date = February 2017 | pmid = 28229088 | pmc = 5305167 | doi = 10.1080/23262133.2017.1283188 }}</ref>

=== Antagonists === * The P2X7 receptor current can be blocked by zinc, calcium, magnesium, and copper.<ref name="North_2002" /> * P2X7 receptors are sensitive to pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) and relatively insensitive to suramin, but the suramin analog, NF279, is much more effective. * Oxidized ATP (OxATP) and Brilliant Blue G has also been used for blocking P2X7 in inflammation.<ref name="Wang_2004">{{cite journal | vauthors = Wang X, Arcuino G, Takano T, Lin J, Peng WG, Wan P, Li P, Xu Q, Liu QS, Goldman SA, Nedergaard M | title = P2X7 receptor inhibition improves recovery after spinal cord injury | journal = Nature Medicine | volume = 10 | issue = 8 | pages = 821–827 | date = August 2004 | pmid = 15258577 | doi = 10.1038/nm1082 | s2cid = 23685403 }}</ref><ref name="Peng_2009">{{cite journal | vauthors = Peng W, Cotrina ML, Han X, Yu H, Bekar L, Blum L, Takano T, Tian GF, Goldman SA, Nedergaard M | title = Systemic administration of an antagonist of the ATP-sensitive receptor P2X7 improves recovery after spinal cord injury | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 30 | pages = 12489–12493 | date = July 2009 | pmid = 19666625 | pmc = 2718350 | doi = 10.1073/pnas.0902531106 | doi-access = free }}</ref> * Other blockers include the large organic cations calmidazolium (a calmodulin antagonist) and KN-62 (a CaM kinase II antagonist).<ref name="North_2002" /> * JNJ-54175446 and JNJ-55308942 are selective antagonists

== Receptor trafficking ==

In microglia, P2X7 receptors are found mostly on the cell surface.<ref name="Boumechache_2009">{{cite journal | vauthors = Boumechache M, Masin M, Edwardson JM, Górecki DC, Murrell-Lagnado R | title = Analysis of assembly and trafficking of native P2X4 and P2X7 receptor complexes in rodent immune cells | journal = The Journal of Biological Chemistry | volume = 284 | issue = 20 | pages = 13446–13454 | date = May 2009 | pmid = 19304656 | pmc = 2679444 | doi = 10.1074/jbc.M901255200 | doi-access = free }}</ref> Conserved cysteine residues located in the carboxyl terminus seem to be important for receptor trafficking to the cell membrane.<ref name="Jindrichova_2012">{{cite journal | vauthors = Jindrichova M, Kuzyk P, Li S, Stojilkovic SS, Zemkova H | title = Conserved ectodomain cysteines are essential for rat P2X7 receptor trafficking | journal = Purinergic Signalling | volume = 8 | issue = 2 | pages = 317–325 | date = June 2012 | pmid = 22286664 | pmc = 3350585 | doi = 10.1007/s11302-012-9291-x }}</ref> These receptors are upregulated in response to peripheral nerve injury.<ref name="Kobayashi_2011">{{cite journal | vauthors = Kobayashi K, Takahashi E, Miyagawa Y, Yamanaka H, Noguchi K | title = Induction of the P2X7 receptor in spinal microglia in a neuropathic pain model | journal = Neuroscience Letters | volume = 504 | issue = 1 | pages = 57–61 | date = October 2011 | pmid = 21924325 | doi = 10.1016/j.neulet.2011.08.058 | s2cid = 32284927 }}</ref>

In melanocytic cells P2X7 gene expression may be regulated by MITF.<ref name="Hoek_2008">{{cite journal | vauthors = Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E | title = Novel MITF targets identified using a two-step DNA microarray strategy | journal = Pigment Cell & Melanoma Research | volume = 21 | issue = 6 | pages = 665–676 | date = December 2008 | pmid = 19067971 | doi = 10.1111/j.1755-148X.2008.00505.x | s2cid = 24698373 | doi-access = free }}</ref>

== Recruitment of pannexin ==

Activation of the P2X7 receptor by ATP leads to recruitment of pannexin pores<ref name="Iglesias_2008">{{cite journal | vauthors = Iglesias R, Locovei S, Roque A, Alberto AP, Dahl G, Spray DC, Scemes E | title = P2X7 receptor-Pannexin1 complex: pharmacology and signaling | journal = American Journal of Physiology. Cell Physiology | volume = 295 | issue = 3 | pages = C752–C760 | date = September 2008 | pmid = 18596211 | pmc = 2544446 | doi = 10.1152/ajpcell.00228.2008 }}</ref> which allow small molecules such as ATP to leak out of cells. This allows further activation of purinergic receptors and physiological responses such a spreading cytoplasmic waves of calcium.<ref name="Boison_2010">{{cite journal | vauthors = Boison D, Chen JF, Fredholm BB | title = Adenosine signaling and function in glial cells | journal = Cell Death and Differentiation | volume = 17 | issue = 7 | pages = 1071–1082 | date = July 2010 | pmid = 19763139 | pmc = 2885470 | doi = 10.1038/cdd.2009.131 }}</ref> Moreover, this could be responsible for ATP-dependent lysis of macrophages through the formation of membrane pores permeable to larger molecules.

== Clinical significance ==

=== Inflammation ===

On T cells activation of P2X7 receptors can activate the T cells or cause T cell differentiation, can affect T cell migration or (at high extracellular levels of ATP and/or NAD+) can induce cell death.<ref name="RivasYanez_2020">{{cite journal | vauthors = Rivas-Yáñez E, Barrera-Avalos C, Bono R, Sauma D | title = P2X7 Receptor at the Crossroads of T Cell Fate | journal = International Journal of Molecular Sciences | volume = 21 | issue = 14 | page = 4937 | date = 2020 | pmid = 32668623 | pmc = 7404255 | doi = 10.3390/ijms21144937 | doi-access = free }}</ref> The CD38 enzyme on B lymphocytes and macrophages reduces extracellular NAD+, promoting the survival of T cells.<ref name="Welsby_2012">{{cite journal | vauthors = Welsby I, Hutin D, Leo O | title = Complex roles of members of the ADP-ribosyl transferase super family in immune defences: looking beyond PARP1 | journal = biochemical Pharmacology | volume = 84 | issue = 1 | pages = 11–20 | date = 2012 | pmid = 22402301 | doi = 10.1016/j.bcp.2012.02.016 }}</ref>

=== Neuropathic pain ===

Microglial P2X7 receptors are thought to be involved in neuropathic pain because blockade or deletion of P2X7 receptors results in decreased responses to pain, as demonstrated ''in vivo''.<ref name="Honore_2006">{{cite journal | vauthors = 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 | title = A-740003 [N-(1-{[(cyanoimino)(5-quinolinylamino) methyl]amino}-2,2-dimethylpropyl)-2-(3,4-dimethoxyphenyl)acetamide], a novel and selective P2X7 receptor antagonist, dose-dependently reduces neuropathic pain in the rat | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 319 | issue = 3 | pages = 1376–1385 | date = December 2006 | pmid = 16982702 | doi = 10.1124/jpet.106.111559 | s2cid = 11352013}}</ref><ref name="Chessell_2005">{{cite journal | vauthors = 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 | title = Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain | journal = Pain | volume = 114 | issue = 3 | pages = 386–396 | date = April 2005 | pmid = 15777864 | doi = 10.1016/j.pain.2005.01.002 | s2cid = 21486673 }}</ref> Moreover, P2X7 receptor signaling increases the release of proinflammatory molecules such as IL-1β, IL-6, and TNF-α.<ref name="Clark_2010">{{cite journal | vauthors = Clark AK, Staniland AA, Marchand F, Kaan TK, McMahon SB, Malcangio M | title = P2X7-dependent release of interleukin-1beta and nociception in the spinal cord following lipopolysaccharide | journal = The Journal of Neuroscience | volume = 30 | issue = 2 | pages = 573–582 | date = January 2010 | pmid = 20071520 | pmc = 2880485 | doi = 10.1523/JNEUROSCI.3295-09.2010 }}</ref><ref name="ShigemotoMogami_2001">{{cite journal | vauthors = Shigemoto-Mogami Y, Koizumi S, Tsuda M, Ohsawa K, Kohsaka S, Inoue K | title = Mechanisms underlying extracellular ATP-evoked interleukin-6 release in mouse microglial cell line, MG-5 | journal = Journal of Neurochemistry | volume = 78 | issue = 6 | pages = 1339–1349 | date = September 2001 | pmid = 11579142 | doi = 10.1046/j.1471-4159.2001.00514.x | s2cid = 44660159 | doi-access = free }}</ref><ref name="Hide_2000">{{cite journal | vauthors = Hide I, Tanaka M, Inoue A, Nakajima K, Kohsaka S, Inoue K, Nakata Y | title = Extracellular ATP triggers tumor necrosis factor-alpha release from rat microglia | journal = Journal of Neurochemistry | volume = 75 | issue = 3 | pages = 965–972 | date = September 2000 | pmid = 10936177 | doi = 10.1046/j.1471-4159.2000.0750965.x | s2cid = 84445342 }}</ref> In addition, P2X7 receptors have been linked to increases in proinflammatory cytokines such as CXCL2 and CCL3.<ref name="Shiratori_2010">{{cite journal | vauthors = Shiratori M, Tozaki-Saitoh H, Yoshitake M, Tsuda M, Inoue K | title = P2X7 receptor activation induces CXCL2 production in microglia through NFAT and PKC/MAPK pathways | journal = Journal of Neurochemistry | volume = 114 | issue = 3 | pages = 810–819 | date = August 2010 | pmid = 20477948 | doi = 10.1111/j.1471-4159.2010.06809.x | s2cid = 25406755 | doi-access = free }}</ref><ref name="Kataoka_2009">{{cite journal | vauthors = Kataoka A, Tozaki-Saitoh H, Koga Y, Tsuda M, Inoue K | title = Activation of P2X7 receptors induces CCL3 production in microglial cells through transcription factor NFAT | journal = Journal of Neurochemistry | volume = 108 | issue = 1 | pages = 115–125 | date = January 2009 | pmid = 19014371 | doi = 10.1111/j.1471-4159.2008.05744.x | s2cid = 205619872 | doi-access = free }}</ref> P2X7 receptors are also linked to P2X4 receptors, which are also associated with neuropathic pain mediated by microglia.<ref name="Boumechache_2009" />

=== Osteoporosis ===

Mutations in this gene have been associated to low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women.<ref name="Gartland_2012">{{cite journal | vauthors = Gartland A, Skarratt KK, Hocking LJ, Parsons C, Stokes L, Jørgensen NR, Fraser WD, Reid DM, Gallagher JA, Wiley JS | title = Polymorphisms in the P2X7 receptor gene are associated with low lumbar spine bone mineral density and accelerated bone loss in post-menopausal women | journal = European Journal of Human Genetics | volume = 20 | issue = 5 | pages = 559–564 | date = May 2012 | pmid = 22234152 | pmc = 3330223 | doi = 10.1038/ejhg.2011.245 }}</ref>

=== Diabetes ===

The ATP/P2X7R pathway may trigger T-cell attacks on the pancreas, rendering it unable to produce insulin. This autoimmune response may be an early mechanism by which the onset of diabetes is caused.<ref>{{cite web | title = Silencing immune attacks in type 1 diabetes | date = June 10, 2013 | url = http://vectorblog.org/2013/06/silencing-immune-attacks-in-type-1-diabetes-without/#more-8597 | access-date = June 15, 2013 }}</ref><ref>{{cite web | title = Boston Children's Hospital Finds Root Cause of Diabetes | date = June 13, 2013 | url = http://www.bostonmagazine.com/health/blog/2013/06/13/boston-childrens-hospital-found-the-root-cause-of-diabetes/ | access-date = June 15, 2013 }}</ref>

==Research==

=== Possible link to hepatic fibrosis ===

One study in mice showed that blockade of P2X7 receptors attenuates onset of liver fibrosis.<ref name=" pmid = 24247209 ">{{cite journal | vauthors = Huang C, Yu W, Cui H, Wang Y, Zhang L, Han F, Huang T | title = P2X7 blockade attenuates mouse liver fibrosis | journal = Molecular Medicine Reports | volume = 9 | issue = 1 | pages = 57–62 | date = January 2014 | pmid = 24247209 | doi = 10.3892/mmr.2013.1807 | url = http://www.spandidos-publications.com/mmr/9/1/57 | doi-access = free }}</ref>

== See also == * Purinergic receptor * P2X receptor

== References == {{Reflist|35em}}

== Further reading == {{refbegin|35em}} * {{cite journal | vauthors = Gartland A, Buckley KA, Hipskind RA, Bowler WB, Gallagher JA | title = P2 receptors in bone--modulation of osteoclast formation and activity via P2X7 activation | journal = Critical Reviews in Eukaryotic Gene Expression | volume = 13 | issue = 2–4 | pages = 237–242 | year = 2003 | pmid = 14696970 | doi = 10.1615/CritRevEukaryotGeneExpr.v13.i24.150 }} * {{cite journal | vauthors = Gartland A, Buckley KA, Bowler WB, Gallagher JA | title = Blockade of the pore-forming P2X7 receptor inhibits formation of multinucleated human osteoclasts in vitro | journal = Calcified Tissue International | volume = 73 | issue = 4 | pages = 361–369 | date = October 2003 | pmid = 12874700 | doi = 10.1007/s00223-002-2098-y | s2cid = 23793221 }} * {{cite journal | vauthors = Bowler WB, Buckley KA, Gartland A, Hipskind RA, Bilbe G, Gallagher JA | title = Extracellular nucleotide signaling: a mechanism for integrating local and systemic responses in the activation of bone remodeling | journal = Bone | volume = 28 | issue = 5 | pages = 507–512 | date = May 2001 | pmid = 11344050 | doi = 10.1016/S8756-3282(01)00430-6 }} * {{cite journal | vauthors = Gartland A, Hipskind RA, Gallagher JA, Bowler WB | title = Expression of a P2X7 receptor by a subpopulation of human osteoblasts | journal = Journal of Bone and Mineral Research | volume = 16 | issue = 5 | pages = 846–856 | date = May 2001 | pmid = 11341329 | doi = 10.1359/jbmr.2001.16.5.846 | s2cid = 37561770 | doi-access = free }} * {{cite journal | vauthors = Gartland A, Buckley KA, Hipskind RA, Perry MJ, Tobias JH, Buell G, Chessell I, Bowler WB, Gallagher JA | title = Multinucleated osteoclast formation in vivo and in vitro by P2X7 receptor-deficient mice | journal = Critical Reviews in Eukaryotic Gene Expression | volume = 13 | issue = 2–4 | pages = 243–253 | year = 2003 | pmid = 14696971 | doi = 10.1615/CritRevEukaryotGeneExpr.v13.i24.160 }} * {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1–2 | pages = 171–174 | date = January 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }} * {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1–2 | pages = 149–156 | date = October 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }} * {{cite journal | vauthors = Gu BJ, Zhang W, Worthington RA, Sluyter R, Dao-Ung P, Petrou S, Barden JA, Wiley JS | title = A Glu-496 to Ala polymorphism leads to loss of function of the human P2X7 receptor | journal = The Journal of Biological Chemistry | volume = 276 | issue = 14 | pages = 11135–11142 | date = April 2001 | pmid = 11150303 | doi = 10.1074/jbc.M010353200 | doi-access = free }} * {{cite journal | vauthors = Kim M, Jiang LH, Wilson HL, North RA, Surprenant A | title = Proteomic and functional evidence for a P2X7 receptor signalling complex | journal = The EMBO Journal | volume = 20 | issue = 22 | pages = 6347–6358 | date = November 2001 | pmid = 11707406 | pmc = 125721 | doi = 10.1093/emboj/20.22.6347 }} * {{cite journal | vauthors = Worthington RA, Smart ML, Gu BJ, Williams DA, Petrou S, Wiley JS, Barden JA | title = Point mutations confer loss of ATP-induced human P2X(7) receptor function | journal = FEBS Letters | volume = 512 | issue = 1–3 | pages = 43–46 | date = February 2002 | pmid = 11852049 | doi = 10.1016/S0014-5793(01)03311-7 | s2cid = 35680551 | bibcode = 2002FEBSL.512...43W }} * {{cite journal | vauthors = Wiley JS, Dao-Ung LP, Gu BJ, Sluyter R, Shemon AN, Li C, Taper J, Gallo J, Manoharan A | title = A loss-of-function polymorphic mutation in the cytolytic P2X7 receptor gene and chronic lymphocytic leukaemia: a molecular study | journal = Lancet | volume = 359 | issue = 9312 | pages = 1114–1119 | date = March 2002 | pmid = 11943260 | doi = 10.1016/S0140-6736(02)08156-4 | s2cid = 6019286 }} * {{cite journal | vauthors = Wilson HL, Wilson SA, Surprenant A, North RA | title = Epithelial membrane proteins induce membrane blebbing and interact with the P2X7 receptor C terminus | journal = The Journal of Biological Chemistry | volume = 277 | issue = 37 | pages = 34017–34023 | date = September 2002 | pmid = 12107182 | doi = 10.1074/jbc.M205120200 | doi-access = free }} * {{cite journal | vauthors = Atkinson L, Milligan CJ, Buckley NJ, Deuchars J | title = An ATP-gated ion channel at the cell nucleus | journal = Nature | volume = 420 | issue = 6911 | page = 42 | date = November 2002 | pmid = 12422208 | doi = 10.1038/420042a | s2cid = 4313025 | doi-access = free }} * {{cite journal | vauthors = Sluyter R, Wiley JS | title = Extracellular adenosine 5'-triphosphate induces a loss of CD23 from human dendritic cells via activation of P2X7 receptors | journal = International Immunology | volume = 14 | issue = 12 | pages = 1415–1421 | date = December 2002 | pmid = 12456589 | doi = 10.1093/intimm/dxf111 | doi-access = free }} * {{cite journal | vauthors = Wiley JS, Dao-Ung LP, Li C, Shemon AN, Gu BJ, Smart ML, Fuller SJ, Barden JA, Petrou S, Sluyter R | title = An Ile-568 to Asn polymorphism prevents normal trafficking and function of the human P2X7 receptor | journal = The Journal of Biological Chemistry | volume = 278 | issue = 19 | pages = 17108–17113 | date = May 2003 | pmid = 12586825 | doi = 10.1074/jbc.M212759200 | doi-access = free }} * {{cite journal | vauthors = Barden JA, Sluyter R, Gu BJ, Wiley JS | title = Specific detection of non-functional human P2X(7) receptors in HEK293 cells and B-lymphocytes | journal = FEBS Letters | volume = 538 | issue = 1–3 | pages = 159–162 | date = March 2003 | pmid = 12633871 | doi = 10.1016/S0014-5793(03)00172-8 | s2cid = 9252812 | doi-access = free | bibcode = 2003FEBSL.538..159B }} * {{cite journal | vauthors = Verhoef PA, Estacion M, Schilling W, Dubyak GR | title = P2X7 receptor-dependent blebbing and the activation of Rho-effector kinases, caspases, and IL-1 beta release | journal = Journal of Immunology | volume = 170 | issue = 11 | pages = 5728–5738 | date = June 2003 | pmid = 12759456 | doi = 10.4049/jimmunol.170.11.5728 | doi-access = free }} * {{cite journal | vauthors = Greig AV, Linge C, Terenghi G, McGrouther DA, Burnstock G | title = Purinergic receptors are part of a functional signaling system for proliferation and differentiation of human epidermal keratinocytes | journal = The Journal of Investigative Dermatology | volume = 120 | issue = 6 | pages = 1007–1015 | date = June 2003 | pmid = 12787128 | doi = 10.1046/j.1523-1747.2003.12261.x }} * {{cite journal | vauthors = Denlinger LC, Sommer JA, Parker K, Gudipaty L, Fisette PL, Watters JW, Proctor RA, Dubyak GR, Bertics PJ | title = Mutation of a dibasic amino acid motif within the C terminus of the P2X7 nucleotide receptor results in trafficking defects and impaired function | journal = Journal of Immunology | volume = 171 | issue = 3 | pages = 1304–1311 | date = August 2003 | pmid = 12874219 | doi = 10.4049/jimmunol.171.3.1304 | doi-access = free }} {{refend}}

== External links == * {{MeshName|P2RX7+protein,+human}}

Category:Ion channels