title: Roles of P2X7 receptor in glial and neuroblastoma cells: the therapeutic potential of P2X7 receptor antagonists.
abstract: Recently, one of the P2 purinergic receptors, the P2X(7) receptor, has been extensively studied in nervous system and important functions have been revealed in both astrocytes and microglia. Stimulation of the receptors induces a sustained and nondesensitized increase in intracellular Ca(2+) concentration ([Ca(2+)](i)). In astrocytes purinergic receptors primarily regulate neurotransmission by inducing gliotransmitters release whereas in microglia the receptors stimulate the processing and release of proinflammation cytokines such as interleukin-1 and are thereby involved in inflammation and neurodegeneration. Thus, P2X(7) receptors are considered not only to exert physiological functions but also mediate cell death. P2X(7) receptors have also been identified in various cancer cells and in neuroblastoma cells. In these cells, the P2X(7) receptor-mediated sustained Ca(2+) signal is important in maintaining cellular viability and growth. Accordingly, these findings not only lead to a better understanding of roles of the receptor but also prompt the development of more potent, selective and safer P2X(7) selective antagonists. These emerging antagonists bring new hope in the treatment of inflammatory-induced neurodegenerative diseases as well as neuroblastoma.
authors.affiliation: Institute of Neuroscience, National Yang Ming University, Taipei, Taiwan, Republic of China. shsun@ym.edu.tw
authors.forename: Synthia H
authors.initials: SH
authors.lastname: Sun
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000502:physiology; D002454:Cell Differentiation; D002470:Cell Survival; D006801:Humans; D009447:Neuroblastoma / Q000378:metabolism*; D009457:Neuroglia / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D058486:Receptors, Purinergic P2X7
chemical_list: D018377:Neurotransmitter Agents; C546468:P2RX7 protein, human; D020033:Protein Isoforms; D058919:Purinergic P2 Receptor Antagonists; D018048:Receptors, Purinergic P2; D058486:Receptors, Purinergic P2X7; D002118:Calcium
references.citation: J Cell Physiol. 1989 Apr;139(1):109-15
references.pmid: 2708449
references.citation: J Neurosci. 2001 Sep 15;21(18):7143-52
references.pmid: 11549725
references.citation: J Neurochem. 1999 Jul;73(1):334-43
references.pmid: 10386986
references.citation: Development. 2005 Jun;132(12):2873-82
references.pmid: 15930116
references.citation: J Immunol. 1996 Feb 15;156(4):1531-9
references.pmid: 8568257
references.citation: J Pharmacol Exp Ther. 2006 Dec;319(3):1376-85
references.pmid: 16982702
references.citation: J Neurosci. 2006 Feb 1;26(5):1378-85
references.pmid: 16452661
references.citation: Br J Pharmacol. 2006 Dec;149(7):880-7
references.pmid: 17031385
references.citation: J Biol Chem. 1987 Jun 25;262(18):8884-8
references.pmid: 3597398
references.citation: J Biol Chem. 1993 Jul 25;268(21):15571-8
references.pmid: 7687997
references.citation: Br J Pharmacol. 2003 Oct;140(3):507-19
references.pmid: 14522842
references.citation: Trends Neurosci. 1990 Feb;13(2):43-6
references.pmid: 1690928
references.citation: Neuropharmacology. 1997 Sep;36(9):1295-301
references.pmid: 9364484
references.citation: J Neurosci. 2003 May 1;23(9):3588-96
references.pmid: 12736329
references.citation: Cancer Res. 2006 Jan 15;66(2):907-14
references.pmid: 16424024
references.citation: J Immunol. 2004 Mar 15;172(6):3399-405
references.pmid: 15004138
references.citation: J Neurosci. 2007 Aug 29;27(35):9525-33
references.pmid: 17728465
references.citation: Bioorg Med Chem Lett. 2003 Nov 17;13(22):4043-6
references.pmid: 14592504
references.citation: Neuroreport. 1996 Nov 4;7(15-17):2533-7
references.pmid: 8981418
references.citation: Eur J Pharmacol. 2006 Nov 21;550(1-3):1-7
references.pmid: 17020759
references.citation: J Neurochem. 2008 Apr;105(1):151-64
references.pmid: 18067549
references.citation: J Immunol. 2006 Apr 1;176(7):3877-83
references.pmid: 16547218
references.citation: Trends Pharmacol Sci. 1998 Mar;19(3):99-107
references.pmid: 9584626
references.citation: J Cell Sci. 2008 Nov 15;121(Pt 22):3717-28
references.pmid: 18987356
references.citation: Neuropharmacology. 1997 Sep;36(9):1285-94
references.pmid: 9364483
references.citation: Br J Pharmacol. 2007 Jul;151(5):571-9
references.pmid: 17471177
references.citation: J Biol Chem. 2001 Jan 5;276(1):125-32
references.pmid: 11016935
references.citation: Mol Pharmacol. 2000 Jul;58(1):82-8
references.pmid: 10860929
references.citation: Eur J Pharmacol. 2002 Jul 5;447(2-3):261-9
references.pmid: 12151017
references.citation: Am J Physiol Cell Physiol. 2003 Aug;285(2):C286-99
references.pmid: 12660148
references.citation: J Immunol. 2000 May 1;164(9):4893-8
references.pmid: 10779799
references.citation: Glia. 2002 Jan;37(1):8-18
references.pmid: 11746779
references.citation: Histopathology. 2004 Mar;44(3):206-15
references.pmid: 14987223
references.citation: Glia. 2009 Apr 15;57(6):622-33
references.pmid: 18942742
references.citation: J Neurochem. 1996 Oct;67(4):1694-701
references.pmid: 8858955
references.citation: J Biol Chem. 2002 Mar 22;277(12):10482-8
references.pmid: 11790776
references.citation: Annu Rev Pharmacol Toxicol. 1995;35:541-79
references.pmid: 7598506
references.citation: Curr Top Med Chem. 2004;4(16):1707-17
references.pmid: 15579103
references.citation: Nat Med. 2004 Aug;10(8):821-7
references.pmid: 15258577
references.citation: J Immunol. 1997 Aug 1;159(3):1451-8
references.pmid: 9233643
references.citation: Physiol Rev. 2002 Oct;82(4):1013-67
references.pmid: 12270951
references.citation: Blood. 2002 Jan 15;99(2):706-8
references.pmid: 11781259
references.citation: Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13644-9
references.pmid: 14597722
references.citation: J Biol Chem. 1999 Nov 19;274(47):33206-8
references.pmid: 10559192
references.citation: J Neurochem. 2002 Oct;83(2):285-98
references.pmid: 12423239
references.citation: EMBO J. 2006 Nov 1;25(21):5071-82
references.pmid: 17036048
references.citation: J Neurosci. 2003 Feb 15;23(4):1320-8
references.pmid: 12598620
references.citation: Cell Signal. 2009 Jun;21(6):881-91
references.pmid: 19385050
references.citation: J Neurosci. 2002 Apr 15;22(8):3061-9
references.pmid: 11943809
references.citation: Bioorg Med Chem Lett. 2008 Mar 15;18(6):2089-92
references.pmid: 18272366
references.citation: J Neurochem. 2004 Jan;88(1):246-56
references.pmid: 14675168
references.citation: Trends Neurosci. 2003 Oct;26(10):536-42
references.pmid: 14522146
references.citation: FEBS J. 2009 Sep;276(18):5307-25
references.pmid: 19682070
references.citation: FEBS Lett. 2003 Mar 13;538(1-3):71-6
references.pmid: 12633855
references.citation: J Biol Chem. 1982 Mar 25;257(6):2834-41
references.pmid: 6460764
references.citation: Neuropharmacology. 1997 Sep;36(9):1127-39
references.pmid: 9364468
references.citation: J Pharmacol Exp Ther. 2008 Dec;327(3):620-33
references.pmid: 18772321
references.citation: Proc Natl Acad Sci U S A. 2009 Jul 28;106(30):12489-93
references.pmid: 19666625
references.citation: Science. 1996 May 3;272(5262):735-8
references.pmid: 8614837