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Encyclopedia of Signaling Molecules pp 3616–3629Cite as

Nucleotide Receptor P2x

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Historical Background

The first evidence of purinergic signaling was described in 1929, when purines were found to underlie physiological responses in the circulatory and digestive system. After 50 years and a wealth of data supporting purine mediated effects in different systems, Burnstock presented the first direct evidence that ATP acts as a transmitter and introduced the concept of purinergic neurotransmission (Burnstock et al. 2010). Thus, ATP was recognized as both an intracellular energy source and an extracellular signaling molecule. Extracellular ATP has been implicated in intercellular communication in a wide variety of cells from different organisms and associated with a diverse array of biological effects. ATP is an ideal molecule for extracellular signaling, it is small, rapidly diffusing, highly unstable due to the presence of extracellular degrading enzymes and not abundant in the extracellular environment at resting conditions (Soto et al. 1997). ATP exerts it actions...

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References

  • Antonio LS, Costa RR, Gomes MD, Varanda WA. Mouse Leydig cells express multiple P2X receptor subunits. Purinergic Signal. 2009;5(3):277–87.

    Article  CAS  PubMed  Google Scholar 

  • Aschrafi A, Sadtler S, Niculescu C, Rettinger J, Schmalzing G. Trimeric architecture of homomeric P2X2 and heteromeric P2X1 + 2 receptor subtypes. J Mol Biol. 2004;342(1):333–43.

    Article  CAS  PubMed  Google Scholar 

  • Ase AR, Bernier LP, Blais D, Pankratov Y, Séguéla P. Modulation of heteromeric P2X1/5 receptors by phosphoinositides in astrocytes depends on the P2X1 subunit. J Neurochem. 2010;113(6):1676–84.

    CAS  PubMed  Google Scholar 

  • Burnstock G, Knight GE. Cellular distribution and functions of P2 receptor subtypes in different systems. Int Rev Cytol. 2004;240:31–304.

    Article  CAS  PubMed  Google Scholar 

  • Burnstock G, Fredholm BB, North RA, Verkhratsky A. The birth and postnatal development of purinergic signalling. Acta Physiol. 2010;199(2):93–147.

    Article  CAS  Google Scholar 

  • Calvert JA, Evans RJ. Heterogeneity of P2X receptors in sympathetic neurons: contribution of neuronal P2X1 receptors revealed using knockout mice. Mol Pharmacol. 2004;65(1):139–48.

    Article  CAS  PubMed  Google Scholar 

  • Cheewatrakoolpong B, Gilchrest H, Anthes JC, Greenfeder S. Identification and characterization of splice variants of the human P2X7 ATP channel. Biochem Biophys Res Commun. 2005;332(1):17–27.

    Article  CAS  PubMed  Google Scholar 

  • De Roo M, Rodeau JL, Schlichter R. Dehydroepiandrosterone potentiates native ionotropic ATP receptors containing the P2X2 subunit in rat sensory neurones. J Physiol. 2003;552(Pt 1):59–71.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Donnelly-Roberts D, McGaraughty S, Shieh CC, Honore P, Jarvis MF. Painful purinergic receptors. J Pharmacol Exp Ther. 2008;324(2):409–15.

    Article  CAS  PubMed  Google Scholar 

  • Donnelly-Roberts DL, Namovic MT, Han P, Jarvis MF. Mammalian P2X7 receptor pharmacology: comparison of recombinant mouse, rat and human P2X7 receptors. Br J Pharmacol. 2009;157(7):1203–14.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Dubyak GR. Go it alone no more–P2X7 joins the society of heteromeric ATP-gated receptor channels. Mol Pharmacol. 2007;72(6):1402–5.

    Article  CAS  PubMed  Google Scholar 

  • Evans RJ, Lewis C, Buell G, Valera S, North RA, Surprenant A. Pharmacological characterization of heterologously expressed ATP-gated cation channels (P2x purinoceptors). Mol Pharmacol. 1995;48(2):178–83.

    CAS  PubMed  Google Scholar 

  • Ford AP, Gever JR, Nunn PA, Zhong Y, Cefalu JS, Dillon MP, Cockayne DA. Purinoceptors as therapeutic targets for lower urinary tract dysfunction. Br J Pharmacol. 2006;147(Suppl 2):S132–43.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Fountain SJ, Burnstock G. An evolutionary history of P2X receptors. Purinergic Signal. 2009;5(3):269–72.

    Article  CAS  PubMed  Google Scholar 

  • Gever JR, Cockayne DA, Dillon MP, Burnstock G, Ford AP. Pharmacology of P2X channels. Pflugers Arch. 2006;452(5):513–37.

    Article  CAS  PubMed  Google Scholar 

  • Guo C, Masin M, Qureshi OS, Murrell-Lagnado RD. Evidence for functional P2X4/P2X7 heteromeric receptors. Mol Pharmacol. 2007;72(6):1447–56.

    Article  CAS  PubMed  Google Scholar 

  • Harhun MI, Povstyan OV, Gordienko DV. Purinoreceptor-mediated current in myocytes from renal resistance arteries. Br J Pharmacol. 2010;160(4):987–97.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Hausmann R, Rettinger J, Gerevich Z, Meis S, Kassack MU, Illes P, Lambrecht G, Schmalzing G. The suramin analog 4,4′,4″,4″′-(carbonylbis(imino-5,1,3-benzenetriylbis (carbonylimino)))tetra-kis-benzenesulfonic acid (NF110) potently blocks P2X3 receptors: subtype selectivity is determined by location of sulfonic acid groups. Mol Pharmacol. 2006;69(6):2058–67.

    Article  CAS  PubMed  Google Scholar 

  • Hechler B, Magnenat S, Zighetti ML, Kassack MU, Ullmann H, Cazenave JP, Evans R, Cattaneo M, Gachet C. Inhibition of platelet functions and thrombosis through selective or nonselective inhibition of the platelet P2 receptors with increasing doses of NF449 [4,4′,4″,4″′-(carbonylbis(imino-5,1,3-benzenetriylbis-(carbonylimino)))tetrakis-benzene-1,3-disulfonic acid octasodium salt]. J Pharmacol Exp Ther. 2005;314(1):232–43.

    Article  CAS  PubMed  Google Scholar 

  • 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. 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. 2006;319(3):1376–85.

    Article  CAS  PubMed  Google Scholar 

  • Hülsmann M, Nickel P, Kassack M, Schmalzing G, Lambrecht G, Markwardt F. NF449, a novel picomolar potency antagonist at human P2X1 receptors. Eur J Pharmacol. 2003;470:1–2):1–7.

    Article  CAS  PubMed  Google Scholar 

  • Jaime-Figueroa S, Greenhouse R, Padilla F, Dillon MP, Gever JR, Ford AP. Discovery and synthesis of a novel and selective drug-like P2X(1) antagonist. Bioorg Med Chem Lett. 2005;15(13):3292–5.

    Article  CAS  PubMed  Google Scholar 

  • Jarvis MF, Khakh BS. ATP-gated P2X cation-channels. Neuropharmacology. 2009;56(1):208–15.

    Article  CAS  PubMed  Google Scholar 

  • Kassack MU, Braun K, Ganso M, Ullmann H, Nickel P, Böing B, Müller G, Lambrecht G. Structure-activity relationships of analogues of NF449 confirm NF449 as the most potent and selective known P2X1 receptor antagonist. Eur J Med Chem. 2004;39(4):345–57.

    Article  CAS  PubMed  Google Scholar 

  • Kawate T, Michel JC, Birdsong WT, Gouaux E. Crystal structure of the ATP-gated P2X(4) ion channel in the closed state. Nature. 2009;460(7255):592–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • King BF. Novel P2X7 receptor antagonists ease the pain. Br J Pharmacol. 2007;151(5):565–7.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • King BF, Knowles ID, Burnstock G, Ramage AG. Investigation of the effects of P2 purinoceptor ligands on the micturition reflex in female urethane-anaesthetized rats. Br J Pharmacol. 2004;142(3):519–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Klapperstück M, Büttner C, Nickel P, Schmalzing G, Lambrecht G, Markwardt F. Antagonism by the suramin analogue NF279 on human P2X(1) and P2X(7) receptors. Eur J Pharmacol. 2000;387(3):245–52.

    Article  PubMed  Google Scholar 

  • Koshimizu TA, Tsujimoto G. Functional role of spliced cytoplasmic tails in P2X2-receptor-mediated cellular signaling. J Pharmacol Sci. 2006;101(4):261–6.

    Article  CAS  PubMed  Google Scholar 

  • Makino T, McLysaght A. Interacting gene clusters and the evolution of the vertebrate immune system. Mol Biol Evol. 2008;25(9):1855–62.

    Article  CAS  PubMed  Google Scholar 

  • Masin M, Kerschensteiner D, Dumke K, Rubio ME, Soto F. Fe65 interacts with P2X2 subunits at excitatory synapses and modulates receptor function. J Biol Chem. 2006;160(2):281–7.

    Google Scholar 

  • Murrell-Lagnado RD, Qureshi OS. Assembly and trafficking of P2X purinergic receptors. Mol Membr Biol. 2008;25(4):321–31.

    Article  CAS  PubMed  Google Scholar 

  • Nicke A, Kuan YH, Masin M, Rettinger J, Marquez-Klaka B, Bender O, Gorecki D, Murrell-Lagnado RD, Soto F. A functional P2X7 splice variant with an alternative transmembrane domain 1 escapes gene inactivation in P2X7 knock-out mice. J Biol Chem. 2009;284(38):25813–22.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • North RA. Molecular physiology of P2X receptors. Physiol Rev. 2002;82(4):1013–67.

    Article  CAS  PubMed  Google Scholar 

  • North RA. Families of ion channels with two hydrophobic segments. Curr Opin Cell Biol. 2006;8(4):474–83.

    Article  Google Scholar 

  • Ralevic V, Burnstock G. Receptors for purines and pyrimidines. Pharmacol Rev. 1998;50(3):413–92.

    CAS  PubMed  Google Scholar 

  • Rettinger J, Schmalzing G, Damer S, Müller G, Nickel P, Lambrecht G. The suramin analogue NF279 is a novel and potent antagonist selective for the P2X(1) receptor. Neuropharmacology. 2000;39(11):2044–53.

    Article  CAS  PubMed  Google Scholar 

  • Rettinger J, Braun K, Hochmann H, Kassack MU, Ullmann H, Nickel P, Schmalzing G, Lambrecht G. Profiling at recombinant homomeric and heteromeric rat P2X receptors identifies the suramin analogue NF449 as a highly potent P2X1 receptor antagonist. Neuropharmacology. 2005;48(3):461–8.

    Article  CAS  PubMed  Google Scholar 

  • Roberts JA, Vial C, Digby HR, Agboh KC, Wen H, Atterbury-Thomas A, Evans RJ. Molecular properties of P2X receptors. Pflugers Arch. 2006;452(5):486–500.

    Article  CAS  PubMed  Google Scholar 

  • Sneddon P, Westfall TD, Todorov LD, Todorova SM, Westfall DP, Nickel P, Kennedy C. The effect of P2 receptor antagonists and ATPase inhibition on sympathetic purinergic neurotransmission in the guinea-pig isolated vas deferens. Br J Pharmacol. 2000;129(6):1089–94.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Soto F, Garcia-Guzman M, Stuhmer W. Cloned ligand-gated channels activated by extracellular ATP (P2X receptors). J Membr Biol. 1997;160(2):91–100.

    Article  CAS  PubMed  Google Scholar 

  • Soto F, Lambrecht G, Nickel P, Stühmer W, Busch AE. Antagonistic properties of the suramin analogue NF023 at heterologously expressed P2X receptors. Neuropharmacology. 1999;38(1):141–9.

    Article  CAS  PubMed  Google Scholar 

  • Surprenant A, North RA. Signaling at purinergic P2X receptors. Annu Rev Physiol. 2009;71:333–59.

    Article  CAS  PubMed  Google Scholar 

  • Zhou S-Y, Mamdani M, Qanud K, Shen J-B, Pappano A, Kumar TS, Jacobson KA, Hintze T, Recchia FA, Liang BT. Treatment of heart failure by a methanocarba derivative of adenosine monophosphate. Implication for a role of cardiac P2X purinergic receptors. J Pharmacol Exp Ther. 2010;333(3):920–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Acknowledgment

F.S. would like to thank Marianela Masin for help with the Figures.

Author information

Authors and Affiliations

  1. Calhoun Cardiovascular Center, University of Connecticut Health Center, 263 Farmington Avenue, Farmington, CT, 06030, USA

    Jian-Bing Shen & Bruce T. Liang

  2. Department of Ophthalmology and Visual Sciences, Washington University in St. Louis, 660 South Euclid Ave, St. Louis, MO, 63110, USA

    Florentina Soto

Authors
  1. Jian-Bing Shen
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  2. Bruce T. Liang
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  3. Florentina Soto
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Corresponding author

Correspondence to Bruce T. Liang .

Editor information

Editors and Affiliations

  1. Department of Molecular Science and Technology, Ajou University, Suwon, Korea

    Sangdun Choi

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Shen, JB., Liang, B.T., Soto, F. (2018). Nucleotide Receptor P2x. In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_50

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