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Physiological Reviews, Vol. 82, No. 4, October 2002, pp. 1013-1067; 10.1152/physrev.00015.2002.
Copyright ©2002 by the American Physiological Society
Institute of Molecular Physiology, University of Sheffield, Western Bank, Sheffield, United Kingdom
North, R. Alan
Molecular Physiology of P2X Receptors. Physiol. Rev. 82: 1013-1067, 2002.
P2X receptors are membrane ion
channels that open in response to the binding of extracellular ATP.
Seven genes in vertebrates encode P2X receptor subunits, which
are 40-50% identical in amino acid sequence. Each subunit has two
transmembrane domains, separated by an extracellular domain (~280
amino acids). Channels form as multimers of several subunits. Homomeric
P2X1, P2X2, P2X3, P2X4, P2X5, and P2X7 channels and heteromeric
P2X2/3 and P2X1/5 channels have been most fully
characterized following heterologous expression. Some agonists (e.g.,
-methylene ATP) and antagonists [e.g., 2',3'-O-(2,4,6-trinitrophenyl)-ATP] are strongly selective
for receptors containing P2X1 and P2X3
subunits. All P2X receptors are permeable to small monovalent cations;
some have significant calcium or anion permeability. 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. P2X receptors are
abundantly distributed, and functional responses are seen in neurons,
glia, epithelia, endothelia, bone, muscle, and hemopoietic tissues. The
molecular composition of native receptors is becoming understood, and
some cells express more than one type of P2X receptor. On smooth
muscles, P2X receptors respond to ATP released from sympathetic motor
nerves (e.g., in ejaculation). On sensory nerves, they are involved in
the initiation of afferent signals in several viscera (e.g., bladder,
intestine) and play a key role in sensing tissue-damaging and
inflammatory stimuli. Paracrine roles for ATP signaling through P2X
receptors are likely in neurohypophysis, ducted glands, airway
epithelia, kidney, bone, and hemopoietic tissues. In the last case,
P2X7 receptor activation stimulates cytokine release by
engaging intracellular signaling pathways.
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T. Noguchi, K. Ishii, H. Fukutomi, I. Naguro, A. Matsuzawa, K. Takeda, and H. Ichijo Requirement of Reactive Oxygen Species-dependent Activation of ASK1-p38 MAPK Pathway for Extracellular ATP-induced Apoptosis in Macrophage J. Biol. Chem., March 21, 2008; 283(12): 7657 - 7665. [Abstract] [Full Text] [PDF]
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S. Adriouch, P. Bannas, N. Schwarz, R. Fliegert, A. H. Guse, M. Seman, F. Haag, and F. Koch-Nolte ADP-ribosylation at R125 gates the P2X7 ion channel by presenting a covalent ligand to its nucleotide binding site FASEB J, March 1, 2008; 22(3): 861 - 869. [Abstract] [Full Text] [PDF]
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A. R. Lorier, J. Lipski, G. D. Housley, J. J. Greer, and G. D. Funk ATP sensitivity of preBotzinger complex neurones in neonatal rat in vitro: mechanism underlying a P2 receptor-mediated increase in inspiratory frequency J. Physiol., March 1, 2008; 586(5): 1429 - 1446. [Abstract] [Full Text] [PDF]
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D. S. K. Samways, K. Migita, Z. Li, and T. M. Egan On the Role of the First Transmembrane Domain in Cation Permeability and Flux of the ATP-gated P2X2 Receptor J. Biol. Chem., February 22, 2008; 283(8): 5110 - 5117. [Abstract] [Full Text] [PDF]
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D. Donnelly-Roberts, S. McGaraughty, C.-C. Shieh, P. Honore, and M. F. Jarvis Painful Purinergic Receptors J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 409 - 415. [Abstract] [Full Text] [PDF]
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K. Dang, K. Lamb, M. Cohen, K. Bielefeldt, and G. F. Gebhart Cyclophosphamide-Induced Bladder Inflammation Sensitizes and Enhances P2X Receptor Function in Rat Bladder Sensory Neurons J Neurophysiol, January 1, 2008; 99(1): 49 - 59. [Abstract] [Full Text] [PDF]
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K. Christenson, L. Bjorkman, C. Tangemo, and J. Bylund Serum amyloid A inhibits apoptosis of human neutrophils via a P2X7-sensitive pathway independent of formyl peptide receptor-like 1 J. Leukoc. Biol., January 1, 2008; 83(1): 139 - 148. [Abstract] [Full Text] [PDF]
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S. R. J. Taylor, M. Gonzalez-Begne, S. Dewhurst, G. Chimini, C. F. Higgins, J. E. Melvin, and J. I. Elliott Sequential Shrinkage and Swelling Underlie P2X7-Stimulated Lymphocyte Phosphatidylserine Exposure and Death J. Immunol., January 1, 2008; 180(1): 300 - 308. [Abstract] [Full Text] [PDF]
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R. Karoly, A. Mike, P. Illes, and Z. Gerevich The Unusual State-Dependent Affinity of P2X3 Receptors Can Be Explained by an Allosteric Two-Open-State Model Mol. Pharmacol., January 1, 2008; 73(1): 224 - 234. [Abstract] [Full Text] [PDF]
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X. Liu, A. Surprenant, H.-J. Mao, S. Roger, R. Xia, H. Bradley, and L.-H. Jiang Identification of Key Residues Coordinating Functional Inhibition of P2X7 Receptors by Zinc and Copper Mol. Pharmacol., January 1, 2008; 73(1): 252 - 259. [Abstract] [Full Text] [PDF]
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D. E. Pafundo, O. Chara, M. P. Faillace, G. Krumschnabel, and P. J. Schwarzbaum Kinetics of ATP release and cell volume regulation of hyposmotically challenged goldfish hepatocytes Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2008; 294(1): R220 - R233. [Abstract] [Full Text] [PDF]
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 V. Vallon P2 receptors in the regulation of renal transport mechanisms Am J Physiol Renal Physiol, January 1, 2008; 294(1): F10 - F27. [Abstract] [Full Text] [PDF]
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D.-J. Jun, J. Kim, S.-Y. Jung, R. Song, J.-H. Noh, Y.-S. Park, S.-H. Ryu, J.-H. Kim, Y.-Y. Kong, J.-M. Chung, et al. Extracellular ATP Mediates Necrotic Cell Swelling in SN4741 Dopaminergic Neurons through P2X7 Receptors J. Biol. Chem., December 28, 2007; 282(52): 37350 - 37358. [Abstract] [Full Text] [PDF]
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C. Coddou, C. Acuna-Castillo, P. Bull, and J. P. Huidobro-Toro Dissecting the Facilitator and Inhibitor Allosteric Metal Sites of the P2X4 Receptor Channel: CRITICAL ROLES OF CYS132 FOR ZINC POTENTIATION AND ASP138 FOR COPPER INHIBITION J. Biol. Chem., December 21, 2007; 282(51): 36879 - 36886. [Abstract] [Full Text] [PDF]
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C. Guo, M. Masin, O. S. Qureshi, and R. D. Murrell-Lagnado Evidence for Functional P2X4/P2X7 Heteromeric Receptors Mol. Pharmacol., December 1, 2007; 72(6): 1447 - 1456. [Abstract] [Full Text] [PDF]
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G. R. Dubyak Go It Alone No More P2X7 Joins the Society of Heteromeric ATP-Gated Receptor Channels Mol. Pharmacol., December 1, 2007; 72(6): 1402 - 1405. [Abstract] [Full Text] [PDF]
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Z. Gerevich, Z. S. Zadori, L. Koles, L. Kopp, D. Milius, K. Wirkner, K. Gyires, and P. Illes Dual Effect of Acid pH on Purinergic P2X3 Receptors Depends on the Histidine 206 Residue J. Biol. Chem., November 23, 2007; 282(47): 33949 - 33957. [Abstract] [Full Text] [PDF]
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L. Cao, M. T. Young, H. E. Broomhead, S. J. Fountain, and R. A. North Thr339-to-Serine Substitution in Rat P2X2 Receptor Second Transmembrane Domain Causes Constitutive Opening and Indicates a Gating Role for Lys308 J. Neurosci., November 21, 2007; 27(47): 12916 - 12923. [Abstract] [Full Text] [PDF]
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A. V. Gourine, N. Dale, E. Llaudet, D. M. Poputnikov, K. M. Spyer, and V. N. Gourine Release of ATP in the central nervous system during systemic inflammation: real-time measurement in the hypothalamus of conscious rabbits J. Physiol., November 15, 2007; 585(1): 305 - 316. [Abstract] [Full Text] [PDF]
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O. S. Qureshi, A. Paramasivam, J. C. H. Yu, and R. D. Murrell-Lagnado Regulation of P2X4 receptors by lysosomal targeting, glycan protection and exocytosis J. Cell Sci., November 1, 2007; 120(21): 3838 - 3849. [Abstract] [Full Text] [PDF]
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R. Sluyter, A. N. Shemon, W. E. Hughes, R. O. Stevenson, J. G. Georgiou, G. D. Eslick, R. M. Taylor, and J. S. Wiley Canine erythrocytes express the P2X7 receptor: greatly increased function compared with human erythrocytes Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2007; 293(5): R2090 - R2098. [Abstract] [Full Text] [PDF]
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L. Li, C. S. Wingo, and S.-L. Xia Downregulation of SGK1 by nucleotides in renal tubular epithelial cells Am J Physiol Renal Physiol, November 1, 2007; 293(5): F1751 - F1757. [Abstract] [Full Text] [PDF]
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 Y. Iwata, Y. Katanosaka, T. Hisamitsu, and S. Wakabayashi Enhanced Na+/H+ Exchange Activity Contributes to the Pathogenesis of Muscular Dystrophy via Involvement of P2 Receptors Am. J. Pathol., November 1, 2007; 171(5): 1576 - 1587. [Abstract] [Full Text] [PDF]
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J.-B. Shen, R. Shutt, A. Pappano, and B. T. Liang Characterization and mechanism of P2X receptor-mediated increase in cardiac myocyte contractility Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H3056 - H3062. [Abstract] [Full Text] [PDF]
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R. Hayato, Y. Ohtubo, and K. Yoshii Functional expression of ionotropic purinergic receptors on mouse taste bud cells J. Physiol., October 15, 2007; 584(2): 473 - 488. [Abstract] [Full Text] [PDF]
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F. Cavaliere, S. Amadio, K. Dinkel, K. G. Reymann, and C. Volonte P2 Receptor Antagonist Trinitrophenyl-Adenosine-Triphosphate Protects Hippocampus from Oxygen and Glucose Deprivation Cell Death J. Pharmacol. Exp. Ther., October 1, 2007; 323(1): 70 - 77. [Abstract] [Full Text] [PDF]
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S. M. Kreda, S. F. Okada, C. A. van Heusden, W. O'Neal, S. Gabriel, L. Abdullah, C. W. Davis, R. C. Boucher, and E. R. Lazarowski Coordinated release of nucleotides and mucin from human airway epithelial Calu-3 cells J. Physiol., October 1, 2007; 584(1): 245 - 259. [Abstract] [Full Text] [PDF]
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C. Wang, Y. Gu, G.-W. Li, and L.-Y. M. Huang A critical role of the cAMP sensor Epac in switching protein kinase signalling in prostaglandin E2-induced potentiation of P2X3 receptor currents in inflamed rats J. Physiol., October 1, 2007; 584(1): 191 - 203. [Abstract] [Full Text] [PDF]
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T. Pangrsic, M. Potokar, M. Stenovec, M. Kreft, E. Fabbretti, A. Nistri, E. Pryazhnikov, L. Khiroug, R. Giniatullin, and R. Zorec Exocytotic Release of ATP from Cultured Astrocytes J. Biol. Chem., September 28, 2007; 282(39): 28749 - 28758. [Abstract] [Full Text] [PDF]
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