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P2RX7  -  purinergic receptor P2X, ligand gated ion...

Homo sapiens

Synonyms: ATP receptor, MGC20089, P2X purinoceptor 7, P2X7, P2Z receptor, ...
 
 
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Disease relevance of P2RX7

 

Psychiatry related information on P2RX7

  • The P2RX7 gene is located within a region on chromosome 12q24.31 that has been identified as a susceptibility locus for affective disorders by linkage and association studies [5].
  • A non-synonymous coding SNP in the P2RX7 gene (rs2230912), previously found to be associated with bipolar disorder, was significantly associated (P=0.0019) with MDD [5].
  • To test whether extracellular ATP can play a role in the neuroimmunopathology of Alzheimer's disease (AD), we evaluated the capacity of the ATP-binding purinoreceptor, P2X7, to modulate cytokine secretion on cultured human macrophages and microglia pre-activated 24 h with the 42 amino acid beta-amyloid peptide (Abeta(1-42)) or lipopolysaccharide [6].
 

High impact information on P2RX7

  • In many cells, activation of homomeric P2X7 receptors induces a permeability increase to larger organic cations including some fluorescent dyes and also signals to the cytoskeleton; these changes probably involve additional interacting proteins [7].
  • In vitro and in vivo activation of the macrophage and microglial cell P2Z/P2X7 receptor by exogenous ATP causes a large and rapid release of mature IL-1 beta [8].
  • Blocking of the P2Z receptor by oxidized ATP also inhibited multinucleated giant cell generation stimulated by concanavalin A or rIFN-gamma without decreasing monocyte migration or membrane adhesion molecule expression [9].
  • ATP receptor regulation of adenylate cyclase and protein kinase C activity in cultured renal LLC-PK1 cells [10].
  • INTERPRETATION: Activation of the P2X7 receptor leads to apoptosis of lymphocytes in individuals with CLL, and reduced function of this receptor has an anti-apoptotic effect, resulting in an increase in B-cell numbers [11].
 

Chemical compound and disease context of P2RX7

  • Reactive Blue 2 improved sensorimotor deficit and restricted the volume of infarction, without preventing the expression of P2X7, but inducing it in the microglia of contralateral frontal and parietal cortex and striatum, which had lost reciprocal connections with the remote infarct area [12].
  • Treatment with 10 nM 17beta-estradiol blocked apoptosis induced by the P2X7-receptor ligands ATP and 2',3'-0-(4-benzoylbenzoyl)-ATP in normal human cervical epithelial cells (hECEs) and attenuated the effect in hECEs immortalized with human papillomavirus-16 (ECE16-1) and the cancer cervical cells HT3 and CaSki [13].
  • Trehalose uptake through P2X7 purinergic channels provides dehydration protection [14].
 

Biological context of P2RX7

  • P2X7 receptors colocalized with anti-caspase-3 antibody and were also expressed in periderm cells positive for TUNEL, suggesting a role in periderm cell apoptosis [15].
  • In this study, we examined the expression and early effects of P2X7 receptor activation on monocyte-derived DC, generated from individuals either wild-type or homozygous for a loss-of-function single nucleotide polymorphism at position 1513 of the P2X7 gene [16].
  • The human P2X7 receptor gene was localized by in situ hybridization to chromosome 12q24 [17].
  • The genomic organization for the human P2X7 receptor gene was determined to comprise 13 exons [17].
  • Furthermore, we argue that aponecrosis as induced by P2X7 is a cell death mechanism with characteristics that potentially have particular relevance to disease pathogenesis [1].
 

Anatomical context of P2RX7

  • NZB and NZW parental strains express the distinct P2X7-L and P2X7-P alleles of P2RX7, respectively, while lymphocytes from these and (NZB x NZW)F1 mice differ markedly in their responses to P2X7 receptor stimulation [1].
  • P2X receptors are ATP-gated ion channels in the plasma membrane, but activation of the P2X7 receptor also leads to rapid cytoskeletal re-arrangements such as membrane blebbing [18].
  • Extracellular ATP triggers IL-1 beta release by activating the purinergic P2Z receptor of human macrophages [19].
  • Extracellular adenosine 5'-triphosphate induces a loss of CD23 from human dendritic cells via activation of P2X7 receptors [16].
  • P2X purinergic receptor channel expression and function in bovine aortic endothelium [20].
 

Associations of P2RX7 with chemical compounds

  • The P2X7 receptor agonist benzoylbenzoyl-adenosine 5'-triphosphate and high concentrations of adenosine 5'-triphosphate (1000-5000 microM) caused a significant reduction in A431 cell number (p<0.001), whereas the P2Y2 receptor agonist uridine 5'-triphosphate caused a significant amount of proliferation (p<0.001) [2].
  • There was a significant decrease in cell number as a result of treatment with the P2X5 receptor agonist ATPgammaS (p<0.001) and the P2X7 receptor agonist BzATP (p<0.001) [21].
  • Addition of ATP also induced a rapid loss of CD23 from the surface of wild-type DC (t(1/2 )< 120 s), and this loss was inhibited by oxidized ATP and KN-62 which are known P2X7 receptor antagonists [16].
  • Also, an LPS-binding domain located in the P2X7 C-terminus appears important for receptor trafficking/function [22].
  • P2X7 receptors control 2-arachidonoylglycerol production by microglial cells [23].
 

Regulatory relationships of P2RX7

  • Glu496 to Ala polymorphism in the P2X7 receptor impairs ATP-induced IL-1 beta release from human monocytes [24].
  • CD39 also decreased the extent of apoptosis triggered by putative type-2X purinergic (P2X7) receptors in response to high concentrations of extracellular ATP in vitro [25].
  • We also demonstrate the ability of P2X7 receptors to stimulate the phosphorylation of CREB, a putative inhibitory transcription factor in microglia [26].
  • We suggest that cell lysis consequent to hP2X7 receptor-induced pore formation contributes to the disorganization and decrease in the amount of contractile myocytes in the media of varicose veins [27].
 

Other interactions of P2RX7

  • Each of the seven identified subunit proteins (P2X1 through P2X7) has been reported to form functional homo-oligomeric channels when expressed in heterologous systems [28].
  • In fetal bladders the expression of P2X1 transcripts was much lower than in adult bladders, and P2X4 and P2X7 were also present [29].
  • RESULTS: The mRNA transcripts of most P2 receptors were detected in primary B cells; the expression of P2X3 and P2X7 receptors was the lowest of all the P2 receptors [30].
  • P2X6 receptors do not express readily, and P2X7 receptors correspond closely in their properties to P2Z [31].
  • Rapid ATP-induced release of matrix metalloproteinase 9 is mediated by the P2X7 receptor [32].
  • These data suggest that increased expression of miR-186 and miR-150 in cancer epithelial cells decreases P2X7 mRNA by activation of miR-186 and miR-150 instability target sites located at the 3'-UTR-P2X7 [33].
 

Analytical, diagnostic and therapeutic context of P2RX7

References

  1. The P2X7 receptor is a candidate product of murine and human lupus susceptibility loci: a hypothesis and comparison of murine allelic products. Elliott, J.I., McVey, J.H., Higgins, C.F. Arthritis Res. Ther. (2005) [Pubmed]
  2. Expression of purinergic receptors in non-melanoma skin cancers and their functional roles in A431 cells. Greig, A.V., Linge, C., Healy, V., Lim, P., Clayton, E., Rustin, M.H., McGrouther, D.A., Burnstock, G. J. Invest. Dermatol. (2003) [Pubmed]
  3. The P2X7 receptor sustains the growth of human neuroblastoma cells through a substance P-dependent mechanism. Raffaghello, L., Chiozzi, P., Falzoni, S., Di Virgilio, F., Pistoia, V. Cancer Res. (2006) [Pubmed]
  4. Chronic treatment with P2-purinergic receptor agonists induces phenotypic modulation of the HL-60 and U937 human myelogenous leukemia cell lines. Cowen, D.S., Berger, M., Nuttle, L., Dubyak, G.R. J. Leukoc. Biol. (1991) [Pubmed]
  5. P2RX7, a gene coding for a purinergic ligand-gated ion channel, is associated with major depressive disorder. Lucae, S., Salyakina, D., Barden, N., Harvey, M., Gagné, B., Labbé, M., Binder, E.B., Uhr, M., Paez-Pereda, M., Sillaber, I., Ising, M., Brückl, T., Lieb, R., Holsboer, F., Müller-Myhsok, B. Hum. Mol. Genet. (2006) [Pubmed]
  6. P2X7 receptor modulation of beta-amyloid- and LPS-induced cytokine secretion from human macrophages and microglia. Rampe, D., Wang, L., Ringheim, G.E. J. Neuroimmunol. (2004) [Pubmed]
  7. Molecular physiology of P2X receptors. North, R.A. Physiol. Rev. (2002) [Pubmed]
  8. Purinergic modulation of interleukin-1 beta release from microglial cells stimulated with bacterial endotoxin. Ferrari, D., Chiozzi, P., Falzoni, S., Hanau, S., Di Virgilio, F. J. Exp. Med. (1997) [Pubmed]
  9. The purinergic P2Z receptor of human macrophage cells. Characterization and possible physiological role. Falzoni, S., Munerati, M., Ferrari, D., Spisani, S., Moretti, S., Di Virgilio, F. J. Clin. Invest. (1995) [Pubmed]
  10. ATP receptor regulation of adenylate cyclase and protein kinase C activity in cultured renal LLC-PK1 cells. Anderson, R.J., Breckon, R., Dixon, B.S. J. Clin. Invest. (1991) [Pubmed]
  11. A loss-of-function polymorphic mutation in the cytolytic P2X7 receptor gene and chronic lymphocytic leukaemia: a molecular study. Wiley, J.S., Dao-Ung, L.P., Gu, B.J., Sluyter, R., Shemon, A.N., Li, C., Taper, J., Gallo, J., Manoharan, A. Lancet (2002) [Pubmed]
  12. P2X7 receptor modulation on microglial cells and reduction of brain infarct caused by middle cerebral artery occlusion in rat. Melani, A., Amadio, S., Gianfriddo, M., Vannucchi, M.G., Volontè, C., Bernardi, G., Pedata, F., Sancesario, G. J. Cereb. Blood Flow Metab. (2006) [Pubmed]
  13. Antiapoptotic effects of estrogen in normal and cancer human cervical epithelial cells. Wang, Q., Li, X., Wang, L., Feng, Y.H., Zeng, R., Gorodeski, G. Endocrinology (2004) [Pubmed]
  14. Trehalose uptake through P2X7 purinergic channels provides dehydration protection. Elliott, G.D., Liu, X.H., Cusick, J.L., Menze, M., Vincent, J., Witt, T., Hand, S., Toner, M. Cryobiology (2006) [Pubmed]
  15. Purinergic receptors are part of a signaling system for keratinocyte proliferation, differentiation, and apoptosis in human fetal epidermis. Greig, A.V., Linge, C., Cambrey, A., Burnstock, G. J. Invest. Dermatol. (2003) [Pubmed]
  16. Extracellular adenosine 5'-triphosphate induces a loss of CD23 from human dendritic cells via activation of P2X7 receptors. Sluyter, R., Wiley, J.S. Int. Immunol. (2002) [Pubmed]
  17. Gene structure and chromosomal localization of the human P2X7 receptor. Buell, G.N., Talabot, F., Gos, A., Lorenz, J., Lai, E., Morris, M.A., Antonarakis, S.E. Recept. Channels (1998) [Pubmed]
  18. Proteomic and functional evidence for a P2X7 receptor signalling complex. Kim, M., Jiang, L.H., Wilson, H.L., North, R.A., Surprenant, A. EMBO J. (2001) [Pubmed]
  19. Extracellular ATP triggers IL-1 beta release by activating the purinergic P2Z receptor of human macrophages. Ferrari, D., Chiozzi, P., Falzoni, S., Dal Susino, M., Melchiorri, L., Baricordi, O.R., Di Virgilio, F. J. Immunol. (1997) [Pubmed]
  20. P2X purinergic receptor channel expression and function in bovine aortic endothelium. Ramirez, A.N., Kunze, D.L. Am. J. Physiol. Heart Circ. Physiol. (2002) [Pubmed]
  21. Purinergic receptors are part of a functional signaling system for proliferation and differentiation of human epidermal keratinocytes. Greig, A.V., Linge, C., Terenghi, G., McGrouther, D.A., Burnstock, G. J. Invest. Dermatol. (2003) [Pubmed]
  22. Purinergic receptor regulation of LPS-induced signaling and pathophysiology. Guerra, A.N., Fisette, P.L., Pfeiffer, Z.A., Quinchia-Rios, B.H., Prabhu, U., Aga, M., Denlinger, L.C., Guadarrama, A.G., Abozeid, S., Sommer, J.A., Proctor, R.A., Bertics, P.J. J. Endotoxin Res. (2003) [Pubmed]
  23. P2X7 receptors control 2-arachidonoylglycerol production by microglial cells. Witting, A., Walter, L., Wacker, J., Möller, T., Stella, N. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  24. Glu496 to Ala polymorphism in the P2X7 receptor impairs ATP-induced IL-1 beta release from human monocytes. Sluyter, R., Shemon, A.N., Wiley, J.S. J. Immunol. (2004) [Pubmed]
  25. CD39 modulates endothelial cell activation and apoptosis. Goepfert, C., Imai, M., Brouard, S., Csizmadia, E., Kaczmarek, E., Robson, S.C. Mol. Med. (2000) [Pubmed]
  26. Purinergic receptors modulate MAP kinases and transcription factors that control microglial inflammatory gene expression. Potucek, Y.D., Crain, J.M., Watters, J.J. Neurochem. Int. (2006) [Pubmed]
  27. P2X7 receptor activation-induced contraction and lysis in human saphenous vein smooth muscle. Cario-Toumaniantz, C., Loirand, G., Ladoux, A., Pacaud, P. Circ. Res. (1998) [Pubmed]
  28. Hetero-oligomeric assembly of P2X receptor subunits. Specificities exist with regard to possible partners. Torres, G.E., Egan, T.M., Voigt, M.M. J. Biol. Chem. (1999) [Pubmed]
  29. A quantitative analysis of purinoceptor expression in human fetal and adult bladders. O'Reilly, B.A., Kosaka, A.H., Chang, T.K., Ford, A.P., Popert, R., Rymer, J.M., McMahon, S.B. J. Urol. (2001) [Pubmed]
  30. Expression of P2 receptors in human B cells and Epstein-Barr virus-transformed lymphoblastoid cell lines. Lee, D.H., Park, K.S., Kong, I.D., Kim, J.W., Han, B.G. BMC Immunol. (2006) [Pubmed]
  31. Functional and molecular diversity of purinergic ion channel receptors. MacKenzie, A.B., Surprenant, A., North, R.A. Ann. N. Y. Acad. Sci. (1999) [Pubmed]
  32. Rapid ATP-induced release of matrix metalloproteinase 9 is mediated by the P2X7 receptor. Gu, B.J., Wiley, J.S. Blood (2006) [Pubmed]
  33. 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. Zhou, L., Qi, X., Potashkin, J.A., Abdul-Karim, F.W., Gorodeski, G.I. J. Biol. Chem. (2008) [Pubmed]
  34. P2X and P2Y purinergic receptors on human intestinal epithelial carcinoma cells: effects of extracellular nucleotides on apoptosis and cell proliferation. Coutinho-Silva, R., Stahl, L., Cheung, K.K., de Campos, N.E., de Oliveira Souza, C., Ojcius, D.M., Burnstock, G. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
 
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