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Nucleotide receptors in the nervous system

An abundant component using diverse transduction mechanisms

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Abstract

Extracellular nucleotides achieve their role as cell-to-cell communicators by acting at cell surface transmembrane receptors—the P2 receptors. Before molecular cloning led to the isolation of any P2-receptor sequence, a small number of receptor types had been proposed on the basis of pharmacological evidence. The application of molecular biology to this field of receptor research has indicated that a great underestimation of the number of receptor subtypes and of their abundance had occurred. There are now known to be seven characterized P2Y (G protein linked) receptors and the same number again of P2X receptors of the transmitter-gated ion channel type. In this review, we discuss the properties of these cloned receptors, their distribution within the nervous system, and their methods of signal transduction.

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References

  • Akbar G. M. K., Dasari V. R., Webb T. E., Ayyanathan K., Pillarisetti K., Sandhu A. K., Athwal R. S., Daniel J. L., Ashby B., Barnard E. A. and Kunapuli S. P. (1996) Molecular cloning of a novel P2 purinoceptor from human erythroleukemia cells.J. Biol. Chem. 271., 18,363–18,367.

    Google Scholar 

  • Ayyanathan K., Naylor S. L., and Kunapuli S. P. (1996a) Structural characterization and fine chromosomal mapping of the human P2Y1 purinergic receptor gene (P2RY1).Somatic Cell Mol. Gen. 22, 419–424.

    Article  CAS  Google Scholar 

  • Ayyanathan K., Webb T. E., Sandhu A. K., Athwal R. S., Barnard E. A., and Kunapuli S. P. (1996b) Cloning and chromosomal localization of the human P2Y1 purinoceptor.Biochem. Biophys. Res. Commun. 218, 783–788.

    Article  PubMed  CAS  Google Scholar 

  • Balachandran C. and Bennett M. R. (1996) ATP-activated cationic and anionic conductances in cultured rat hippocampal neurones.Neurosci. Lett. 204, 73–76.

    Article  PubMed  CAS  Google Scholar 

  • Balcar V. J., Li Y., Killinger S., and Bennet M. R. (1995) Autoradiography of P2X receptors in the rat brain.Br. J. Pharmacol. 115, 302–306.

    PubMed  CAS  Google Scholar 

  • Barnard E. A. (1996) The transmitter-gated channels: a range of receptor types and structures.Trends Pharmacol. Sci. 17, 305–309.

    Article  PubMed  CAS  Google Scholar 

  • Barnard E. A., Webb T. E., Simon J., and Kunapuli S. P. (1996) The diverse series of recombinant P2Y purinoceptors, inCiba Foundation Symposia vol. 198 Wiley, Chichester, UK, pp. 166–188.

    Google Scholar 

  • Benham C. D. and Tsien R. W. (1987) A novel receptor-operated Ca2+-permeable channel activated by ATP in smooth muscle.Nature 328, 275–278.

    Article  PubMed  CAS  Google Scholar 

  • Benninger C., Kadis J., and Prince D. A. (1980) Extracellular calcium and potassium changes in hippocampal slices.Brain Res. 187, 165–182.

    Article  PubMed  CAS  Google Scholar 

  • Bogdanov Y. D., Dale L., King B. F., Whittock N., and Burnstock G. (1997) Early expression of a novel nucleotide receptor in the neural plate of Xenopus embryos.J. Biol. Chem. 272, 12,583–12,590.

    Article  CAS  Google Scholar 

  • Bo X., Simon J., Burnstock G., and Barnard E. A. (1992) Solubilisation and molecular size determination of the P2X purinoceptor from rat vas deferens.J. Biol. Chem. 267, 17,581–17,587.

    CAS  Google Scholar 

  • Bo X. and Burnstock G. (1994) Distribution of [3H]αβ-methylene ATP binding sites in rat brain and spinal cord.Neuroreport 5, 160–164.

    Article  Google Scholar 

  • Bo X., Zhang Y., Nassar M., Burnstock G., and Schoepfer R. A. (1995) P2X purinoceptor cDNA conferring a novel pharmacological profile.FEBS Lett. 375, 129–133.

    Article  PubMed  CAS  Google Scholar 

  • Boyer J. L., Lazarowski E. R., Chen X., and Harden T. K. (1993) Identification of a P2Y-purinergic receptor that inhibits adenylate cyclase.J. Pharmacol. Exp. Ther. 267, 1140–1146.

    PubMed  CAS  Google Scholar 

  • Boyer J. L., Otuel J. W., Fischer B., Jacobson K. A., and Harden T. K. (1995) Potent agonist action of 2-thioether derivatives of adenine-nucleotides at adenylyl cyclase-linked p-2y-purinoceptors.Br. J. Pharmacol. 116, 2611–2616.

    PubMed  CAS  Google Scholar 

  • Boyer J. L., Zohn I. E., Jacobson K. A., and Harden T. K. (1994) Differential effects of P2-purinoceptor antagonists on phospholipase C-and adenylate cyclase-coupled P2Y-purinoceptors.Br. J. Pharmacol. 113, 614–620.

    PubMed  CAS  Google Scholar 

  • Brake A. J., Wagenbach M. J., and Julius D. (1994) New structural motif for ligand-gated ion channels defined by an ionotropic ATP receptor.Nature 371, 519–523.

    Article  PubMed  CAS  Google Scholar 

  • Brändle U., Spielmanns P., Osteroth R., Sim J., Surprenant A., Buell G. N., Ruppersberg J. P., Plinkert P. K., Zenner H.-P., and Glowatzki E. (1997) Desensitization of the P2X2 receptor controlled by alternative splicing.FEBS Lett. 404, 294–298.

    Article  PubMed  Google Scholar 

  • Buell G. N., Lewis C., Collo G., North R. N., and Surprenant A. (1996) An antagonist-insensitive P2X receptor expressed in epithelia and brain.EMBO J. 15, 55–62.

    PubMed  CAS  Google Scholar 

  • Buell G. N., Talabot F., Gos A., Lorenz, J., Lai E., Morris M. A., and Antonarakis S. E. (1997) Gene structure and chromosomal localization of the human P2X7 receptor.Recept. Channels #5 (in press).

  • Burnstock G. (1972) Purinergic nerves.Pharmacol. Rev. 42, 509–581.

    Google Scholar 

  • Burnstock G. and Kennedy C. (1985) Review: Is there a basis for distinguishing two types of P2 purinoceptor?Gen. Pharmacol. 5, 433–440.

    Google Scholar 

  • Chang K., Hanaoka K., Kumada M., and Takuwa Y. (1995) Molecular cloning and functional analysis of a novel P2 nucleotide receptor.J. Biol. Chem. 270, 26,152–26,158.

    CAS  Google Scholar 

  • Charlton S. J., Brown C. A., Weisman G. A., Turner J. T., Erb L., and Boarder M. R. (1996a) PPADS and suramin as antagonists at cloned P2Y-purinoceptors and P2U-purinoceptors.Br. J. Pharmacol. 118, 704–710.

    PubMed  CAS  Google Scholar 

  • Charlton S. J., Brown C. A., Weisman G. A., Turner J. T., Erb L., and Boarder M. R. (1996b) Cloned and transfected P2Y4 receptors—characterization of a suramin and PPADS-insensitive response to UTP.Br. J. Pharmacol. 119, 1301–1303.

    PubMed  CAS  Google Scholar 

  • Chen B. C., Lee C. M., and Lin W. W. (1996) Inhibition of ecto-ATPase by PPADS, suramin and reactive blue in endothelial cells, C-6 glioma cells and RAW 264.7 macrophages.Br. J. Pharmacol. 119, 1628–1634.

    PubMed  CAS  Google Scholar 

  • Chen C., Akopian A. N., Sivilotti L., Colquhoun D., Burnstock G., and Wood J. N. (1995) A P2X purinoceptor expressed by a subset of sensory neurones.Nature 377, 428–430.

    Article  PubMed  CAS  Google Scholar 

  • Chen Z.-P., Lewy A., and Lightman S. L. (1994) Activation of specific ATP receptors induces a rapid increase in intracellular calcium ions in rat hypothalamic neurons.Brain Res. 641, 249–256.

    Article  PubMed  CAS  Google Scholar 

  • Chen Z.-P., Lewy A., and Lightman S. L. (1995) Nucleotides as extracellular signalling molecules.J. Neuroendocrinol. 7, 83–96.

    Article  PubMed  CAS  Google Scholar 

  • Chen Z.-P., Krull N., Xu S., Levy A., and Lightman S. L. (1996) Molecular cloning and functional characterization of a rat pituitary G protein-coupled ATP receptor.Endocrinology 137, 1833–1840.

    Article  PubMed  CAS  Google Scholar 

  • Chessell I. P., Michel A. D., and Humphrey P. P. A. (1997) Functional evidence for multiple purinoceptor subtypes in rat medial vestibular nucleus.Neuroscience 77, 783–791.

    Article  PubMed  CAS  Google Scholar 

  • Collo G., North R. A., Kawashima E., Merlo-Pich E., Neidhart S., Surprenant A., and Buell G. N. (1996) Cloning of P2X5 and P2X6 receptors and the distribution and properties of an extended family of ATP-gated ion channels.J. Neurosci. 16, 2495–2507.

    PubMed  CAS  Google Scholar 

  • Communi D., Motte S., Boyenaems J.-M., and Pirotton S. (1992a) Pharmacological characterization of the human P2Y4 receptor.Eur J. Pharmacol. 317, 383–389.

    Article  Google Scholar 

  • Communi D., Parmentier M., and Boeynaems J.-M. (1996b) Cloning, functional expression and tissue distribution of the human P2Y6 receptor.Biochem. Biophys. Res. Commun. 222, 303–308.

    Article  PubMed  CAS  Google Scholar 

  • Communi D., Pirotton S., Parmentier M., and Boeynaems J.-M. (1995) Cloning and functional expression of a human uridine nucleotide receptor.J. Biol. Chem. 270, 30,849–30,852.

    CAS  Google Scholar 

  • Cook S. P., Vulchanova L., Hargreaves K. M., Elde R., and McCleskey M. C. (1997) Distinct ATP receptors on pain-sensing and stretch-sensing neurons.Nature 387, 505–508.

    Article  PubMed  CAS  Google Scholar 

  • Dasari V. R., Sandhu A. K., Mills D. C. B., Athwal R. S., and Kunapuli S. P. (1996) Mapping of the P2U purinergic receptor gene to human chromosome 11q13.5–14.1.Somatic Cell Mol. Gen. 22, 75–79.

    Article  CAS  Google Scholar 

  • Dubyak G. R. and El-Moatassim C. (1993) Signal-transduction via P2-purinergic receptors for extracellular ATP and other nucleotides.Am. J. Physiol. 265, C577-C606.

    PubMed  CAS  Google Scholar 

  • Dubyak G. R. and Fedan J. S., eds. (1990)Biological Actions of Extracellular ATP, Annals of the New York Academy of Sciences, vol. 603, New York Academy of Sciences, New York.

    Google Scholar 

  • Edwards F. A., Gibb A. J., and Colquhoun D. (1992) ATP receptor-mediated synaptic currents in the central nervous system.Nature 359, 144–147.

    Article  PubMed  CAS  Google Scholar 

  • Enomoto K., Furuya K., Moore R. C., Yamagishi S., Oka T., and Maeno T. (1996) Expression cloning and signal-transduction pathway of P2U receptor in mammary-tumor cells.Biological Signals 5, 9–21.

    Article  PubMed  CAS  Google Scholar 

  • Evans R. J., Derkach V., and Surprenant A. (1992) ATP mediates fast synaptic transmission in mammalian neurons.Nature 357, 503–505.

    Article  PubMed  CAS  Google Scholar 

  • Filippov A. K. and Brown D. A. (1996) Activation of nucleotide receptors inhibits high-threshold calcium currents in NG108-15 neuronal hybrid-cells.Eur. J. Neurosci. 8, 1149–1155.

    Article  PubMed  CAS  Google Scholar 

  • Filippov A. K., Selyanko A. A., Robbins J., and Brown D. A. (1994) Activation of nucleotide receptors inhibits M-type K+-current IKM in neuroblastoma x glioma hybrid-cells.Eur. J. Physiol. 429, 223–230.

    Article  CAS  Google Scholar 

  • Filippov A. K., Webb T. E., Barnard E. A., and Brown D. A. (1997) Heterologously-expressed P2Y2 nucleotide receptors inhibit N-type calcium currents in rat sympathetic neurons.Br. J. Pharmacol. 121, 849–852.

    Article  PubMed  CAS  Google Scholar 

  • Filtz T. M., Li Q., Boyer J. L., Nicholas R. A., and Harden T. K. (1994) Expression of a cloned P2Y purinergic receptor that couples to phospholipase C.Mol. Pharmacol. 46, 8–4.

    PubMed  CAS  Google Scholar 

  • Fredholm B. B., Abbracchio M. P., Burnstock G., Daly J. W., Harden T. K., Jacobson K. A., Leff P., and Williams M. (1994) VI. Nomenclature and classification of purinoceptors.Pharmacol. Rev. 46, 143–156.

    PubMed  CAS  Google Scholar 

  • Fröhlich R., Boehm S., and Illes P. (1996) Pharmacological characterization of P2 purinoceptor types in rat locus coeruleus neurons.Eur. J. Pharmacol. 315, 255–261.

    Article  PubMed  Google Scholar 

  • Garcia-Guzman M., Soto F., Laube B., and Stühmer W. (1996) Molecular cloning and functional expression of a novel rat heart P2X purinoceptor.FEBS Lett. 388, 123–127.

    Article  PubMed  CAS  Google Scholar 

  • Garcia-Guzman M., Soto F., Gomez-Hernandez M. J. Lund P. E., and Stühmer W. (1997) Characterization of recombinant human P2X4 receptor reveals pharmacological difference to the rat homologue.Mol. Pharmacol. 51, 109–118.

    PubMed  CAS  Google Scholar 

  • Harden T. K., Boyer J. L., and Nicholas R. A. (1995) P2-purinergic receptor: Subtype-associated signaling responses and structure.Annu. Rev. Pharmacol. Toxicol. 35, 541–579.

    Article  PubMed  CAS  Google Scholar 

  • Henderson D. J., Elliot D. G., Smith G. M., Webb T. E., and Dainty I. A. (1995) Cloning and characterization of a bovine P2Y receptor.Biochem. Biophys. Res. Commun. 212, 648–656.

    Article  PubMed  CAS  Google Scholar 

  • Higgins D. G. and Sharp P. M. (1988) CLUSTAL: a package for performing multiple sequence alignments on a microcomputer.Gene 73, 237–244.

    Article  PubMed  CAS  Google Scholar 

  • Ho C., Hicks J. L., and Salter M. W. (1995) A novel P2-purinoceptor expressed by a subpopulation of astrocytes from the dorsal spinal cord of the rat.Br. J. Pharmacol. 116, 2909–2918.

    PubMed  CAS  Google Scholar 

  • Ikeuchi Y. and Nishizaki T. (1996) P2 purinoceptor-operated potassium channel in rat cerebellar neurons.Biochem. Biophys. Res. Commun. 218, 67–71.

    Article  PubMed  CAS  Google Scholar 

  • Ikeuchi Y. and Nishizaki T. (1995) The P2Y purinoceptor-operated potassium channel is possibly regulated by the βγ subunits of a pertussis toxin-insensitive G-protein in cultured rat inferior colliculus neurons.Biochem. Biophys. Res. Commun. 214, 589–596.

    Article  PubMed  CAS  Google Scholar 

  • Ikeuchi Y., Nishizaki T., Mori M., and Okada Y. (1996) Adenosine activates the K+ channel and enhances cytosolic Ca2+ release via a P2Y purinoceptor in hippocampal neurons.Eur. J. Pharmacol. 304, 191–200.

    Article  PubMed  CAS  Google Scholar 

  • Illes P., Nieber K., and Norenberg W. (1997) Electrophysiological effects of ATP on brain neurones.J. Autonomic Pharmacol. 16, 407–411.

    Google Scholar 

  • Janssens R., Communi D., Pirotton S., Samson M., Parmentier M., and Boyenaems J.-M. (1996) Cloning and tissue distribution of the human P2Y1 receptor.Biochem. Biophys. Res. Commun. 221, 588–593.

    Article  PubMed  CAS  Google Scholar 

  • Janssens R., Boeynaems J.-M., Godart M., and Communi D. (1997) Cloning of a human heptahelical receptor closely related to the p2y5 receptor.Biochem. Biophys. Res. Commun. 236, 106–112.

    Article  PubMed  CAS  Google Scholar 

  • Kaplan M. H., Smith D. I., and Sundick R. S. (1993) Identification of a G-protein coupled receptor-induced in activated T-cells.J. Immunol. 151, 628–638.

    PubMed  CAS  Google Scholar 

  • Kastritsis C. H. C., Salm A. K., and Mccarthy K. (1992) Stimulation of the P2Y purinergic receptor on type-1 astroglia results in inositol phosphate formation and calcium mobilization.J. Neurochem. 58, 1277–1284.

    Article  PubMed  CAS  Google Scholar 

  • Kennedy C. and Leff P. (1995) How should P2X purinoceptors be classified pharmacologically?Trends Pharmacol. Sci. 16, 168–173.

    Article  PubMed  CAS  Google Scholar 

  • Kidd E. J., Grahames C. B. A., Simon J., Michel A. D., Barnard E. A., and Humphrey P. P. A. (1995) Localization of P2X purinoceptor transcripts in the rat nervous system.Mol. Pharmacol. 48, 569–573.

    PubMed  CAS  Google Scholar 

  • Kirischuk S., Moller T., Voitenko N., Kettenmann H., and Verkhratsky A. (1995a) ATP-induced cytoplasmic calcium mobilization in Bergmann glial cells.J. Neurosci. 15, 7861–7871.

    PubMed  CAS  Google Scholar 

  • Kirischuk S., Scherer J., Kettenmann H., and Verkhratsky A. (1995b) Activation of P2-purinoceptors triggers Ca2+ release from InsP3-sensitive stores in mammalian oligodendrocytes.J. Physiol. 483, 41–57.

    PubMed  CAS  Google Scholar 

  • Khakh B. S., Humphrey P. P. A., and Surprenant A. (1995) Electrophysiological properties of P2X − purinoceptors in rat superion cervical, nodose and guinea pig coeliac neurones.J. Physiol. 484, 385–395.

    PubMed  CAS  Google Scholar 

  • Khakh B. S., Humphrey P. P. A., and Henderson G. (1997) ATP-gated cation channels (P2X purinoceptors) in trigeminal mesencephalic nucleus of the rat.J. Physiol. 498, 709–715.

    PubMed  CAS  Google Scholar 

  • Kraig R. T. and Nicholson C. (1978) Extracellular ionic variations during spreading depression.Neuroscience 3, 1045–1059.

    Article  PubMed  CAS  Google Scholar 

  • Krishtal O. A., Marchenko S. M., and Obukov A. G. (1988) Cationic channels activated by extracellular ATP in rat sensory neurons.Neuroscience 27, 995–1000.

    Article  PubMed  CAS  Google Scholar 

  • Langley D. and Pearce B. (1996) Purine- and pyrimidine nucleotide-stimulated changes in intracellular calcium concentration in cultured astrocytes.Receptors Channels 4, 253–259.

    PubMed  CAS  Google Scholar 

  • Langosch J. M., Gebicke-Haerter P. J., Nörenberg W., and Illes P. (1994) Characterization and transduction mechanism of purinoceptors in activated rat microglia.Br. J. Pharmacol. 113, 29–34.

    PubMed  CAS  Google Scholar 

  • Lazarowski E. R., Watt W. C., Stutts M. J., Boucher R. C., and Harden T. K. (1995) Pharmacological selectivity of the cloned human P2U-purinoceptor-potent activation by diadenosine tetraphosphate.Br. J. Pharmacol. 116, 1619–1627.

    PubMed  CAS  Google Scholar 

  • Léon C., Hechler B., Vial C., Leray C., Cazevane J.-P., and Gachet C. (1997) The P2Y1 receptors is an ADP receptor antagonized by ATP and expressed in platelets and megakaryoblastic cells.FEBS Lett. 403, 26–30.

    Article  PubMed  Google Scholar 

  • Léon C., Vial C., Cazenave J.-P., and Gachet C. (1996) Cloning and sequencing of a human cDNA encoding endothelial P2Y1 purinoceptor.Gene 171, 295–297.

    Article  PubMed  Google Scholar 

  • Lewis C., Neidhart S., Holy C., North R. A., Buell G. N., and Surprenant A. (1995) Heteropolymerization of P2X receptor subunits can account for ATP-gated currents in sensory neurons.Nature 377, 432–435.

    Article  PubMed  CAS  Google Scholar 

  • Lin W. W. and Chuang D. M. (1994) Different signal-transduction pathways are coupled to the nucleotide receptor and the P2Y receptor in C6 glioma-cells.J. Pharmacol. Exp. Ther. 269, 926–931.

    PubMed  CAS  Google Scholar 

  • Longhurst P. A., Schwege T., Folander K., and Swanson R. (1996) The human P2X1 receptor: molecular cloning, tissue distribution, and localization to chromosome 17.Biochim. Biophys. Acta 1308, 185–188.

    PubMed  Google Scholar 

  • Lustig K. D., Shiau A. K., Brake A. J., and Julius D. (1993) Expression cloning of an ATP receptor from mouse neuroblastoma cells.Proc. Natl. Acad. Sci. USA,90, 5113–5117.

    Article  PubMed  CAS  Google Scholar 

  • McGeer P. L. and McGeer E. G. (1995) The inflammatory response system of brain: implications for therapy of Alzheimer and other neurodegenerative diseases.Brain Dev. Res. 21, 195–218.

    Article  CAS  Google Scholar 

  • Michel A. D. and Humphrey P. P. A. (1994) Effects of metal cations on [3H]-α,β methylene ATP binding in rat vas deferens.Naunyn Schmiedeberg's Arch. Pharmacol. 350, 113–122.

    CAS  Google Scholar 

  • Michel A. D. and Humphrey P. P. A. (1996a) High affinity P2x purinoceptor binding sites for [35S]adenosine 5′-o-[3-thiotriphosphate] in rat vas deferens membranes.Br. J. Pharmacol. 117, 63–70.

    PubMed  CAS  Google Scholar 

  • Michel A. D., Lundström K., Buell G. N., Surprenant A., Valera S., and Humphrey P. P. A. (1996b) The binding characteristics of a human bladder recombinant P2X purinoceptor, labelled with [3H]-α,βme ATP, [35S]-ATPγS or [33P]-ATP.Br. J. Pharmacol.,117, 1254–1260.

    PubMed  CAS  Google Scholar 

  • Michel A. D., Lundström K., Buell G. N., Surprenant A., Valera S., and Humphrey P. P. A. (1996c) A comparison of the binding characteristics of recombinant P2X1 and P2X2 purinoceptors.Br. J. Pharmacol. 118, 1806–1812.

    PubMed  CAS  Google Scholar 

  • Michel A. D., Miller K. J., Lundström K., Buell G. N., and Humphrey P. P. A. (1997) Radiolabeling of the rat P2X4 purinoceptor: evidence for allosteric interactions of purinoceptor antagonists and monovalent cations with P2X purinoceptors.Mol. Pharmacol. 51, 524–532.

    PubMed  CAS  Google Scholar 

  • Mironov S. L. (1994) Metabotropic ATP receptor in hippocampal and thalamic neurones: pharmacological and modulation of Ca2+ mobilizing mechanisms.Neuropharmacol. 33, 1–13.

    Article  CAS  Google Scholar 

  • Motin L. and Bennett M. R. (1995) Effect of P2-purinoceptor antagonists on glutamatergic transmission on the rat hippocampus.Br. J. Pharmacol. 115, 1276–1280.

    PubMed  CAS  Google Scholar 

  • Nakamura F. and Strittmatter S. M. (1996) P2Y1 purinergic receptors in sensory neurons: contibutions to touch-induced impulse generation.Proc. Natl. Acad. Sci. USA 93, 10,465–10,470.

    CAS  Google Scholar 

  • Neary J. T. and Zhu Q. (1994) Signaling by ATP receptors in astrocytes.Neuroreport 5, 1617–1620.

    Article  PubMed  CAS  Google Scholar 

  • Neary J. T., Rathbone M. P., Cattabeni F., Abbracchio M. P., and Burnstock G. (1996) Trophic actions of extracellular nucleotides and nucleosides on glial and neuronal cells.Trends Neurosci.19, 13–18.

    Article  PubMed  CAS  Google Scholar 

  • Nicholas R. A., Watt W. C., Lazarowski E. R., Li Q., and Harden T. K. (1996) Uridine nucleotide selectivity of 3 phospholipase C-activating P2Y receptors—identification of a UDP-selective, a UTP-selective, and an ATP-specific and UTP-specific receptor.Mol. Pharmacol. 50, 224–229.

    PubMed  CAS  Google Scholar 

  • Nishizaki T. and Ikeuchi Y. (1996) Adenosine evokes potassium currents by protein kinase C activated via a novel signaling pathway in superior colliculus neurons.FEBS Lett. 378, 1–6.

    Article  PubMed  CAS  Google Scholar 

  • Nguyen T., Erb L., Weisman G. A., Marchese A., Heng H. H. Q., Garrad R. C., George S. R., Turner J. T., and O'Dowd B. F. (1995) Cloning, expression and chromosomal localization of the human uridine nucleotide receptor.J. Biol. Chem. 270, 30,845–30,848.

    CAS  Google Scholar 

  • North R. A. (1996) Families of ion channels with two hydrophobic segments.Curr. Opin. Cell. Biol. 8, 474–483.

    Article  PubMed  CAS  Google Scholar 

  • North R. A. and Barnard E. A. (1997) Purinergic receptors for ATP.Curr. Opin. Neurobiol.,7, 346–357.

    Article  PubMed  CAS  Google Scholar 

  • Nuttle L. C. and Dubiak G. R. (1994) Differential activation of cation channels and non-selective pores by macrophage P2Z purinergic receptors expressed inXenopus oocytes.J. Biol. Chem. 269, 13,988–13,996.

    CAS  Google Scholar 

  • O'Connor S. E., Dainty I. A., and Leff P. (1991) Further subclassification of ATP receptors based on agonist studies.Trends Pharmacol. Sci. 12, 137–140.

    Article  PubMed  Google Scholar 

  • Parr C. E., Sullivan D. M., Paradiso A. M., Lazarowski E. R., Burch L. H., Olsen J. C., Erb L., Weissman G., Boucher R. C., and Turner J. T. (1994) Cloning and expression of a human P2U nucleotide receptor, a target for cystic fibrosis pharmacology.Proc. Natl. Acad. Sci. USA 91, 3275–3279.

    Article  PubMed  CAS  Google Scholar 

  • Rassendren F., Buell G. N., Virgino C., Collo G., North R. A., and Surprenant A. (1997) The permeabilizing ATP receptor, P2X7. Cloning and expeession of a human cDNA.J. Biol. Chem. 272, 5482–5488.

    Article  PubMed  CAS  Google Scholar 

  • Rice W. R., Burton F. M., and Fiedeldey D. T. (1995) Cloning and expression of the alveolar type II cell P2U-purinergic receptor.Am. J. Respir. Cell. Mol. Biol. 12, 27–32.

    PubMed  CAS  Google Scholar 

  • Rotin D., Bar-Sagi D., O'Brodovich H., Merilainen J., Lehto V. P., Canessa C. M., Rossier B. C., and Downey G. P. (1994) An SH3 binding region in the epithelial Na+ channel (αENaC), mediates its localization at the apical membrane.EMBO J. 13, 4440–4450.

    PubMed  CAS  Google Scholar 

  • Salter M. W. and Hicks J. L. (1995) ATP causes release of intracellular Ca2+ via the phospholipase c-beta/IP3 pathway in astrocytes from the dorsal spinal-cord.J. Neurosci. 15, 2961–2971.

    PubMed  CAS  Google Scholar 

  • Salter M. W. and Hicks J. L. (1994) ATP-evoked increses in intracellular calcium in neurons and glia from the dorsal spinal horn.J. Neurosci. 14, 1563–1575.

    PubMed  CAS  Google Scholar 

  • Saraste M., Sibbald P. R., and Wittinghofer A. (1990) The P-loop—a common motif in ATP-binding and GTP-binding proteins.Trends Biol. Sci. 15, 430–434

    Article  Google Scholar 

  • Schachter J. B., Li Q., Boyer J. L., Nicholas R. A., and Harden T. K. (1996). Second messenger cascade specificity and pharmacological selectivity of the human P2Y1-purinoceptor.Br. J. Phamacol. 118, 167–173.

    CAS  Google Scholar 

  • Schachter J. B. and Harden T. K. (1997) An examination of deoxyadenosine 5′ (α-thio)triphosphate as a ligand to define P2Y receptors and its selectivity as a low potency partial agonist of the P2Y1 receptor.Br. J. Pharmacol. 121, 338–344.

    Article  PubMed  CAS  Google Scholar 

  • Schlosser S. F., Burgstahler A. D., and Nathanson M. H. (1996) Isolated rat hepatocytes can signal to other hepatocytes and bile duct cells by release of nucleotides.Proc. Natl. Acad. Sci. USA 93, 12,020–12,025.

    Article  Google Scholar 

  • Séguéla P., Haghighi A., Soghomonian J.-J., and Cooper E. (1996) A novel neuronal P2X ATP receptor ion channel with widespread distribution in the brain.J. Neurosci. 1, 448–455.

    Google Scholar 

  • Shen K. Z. and North R. A. (1993) Excitation of rat locus coeruleus neurons by adenosine 5′-triphosphate: ionic mechanism and receptor characterisation.J. Neurosci. 13, 894–899.

    PubMed  CAS  Google Scholar 

  • Soto F., Garcia-Guzman M., Gomez-Hernandez J. M., Hollmann M., Karschin C., and Stuhmer W. (1996) P2Xα4: an ATP-activated ionotropic receptor cloned from rat brain.Proc. Natl. Acad. Sci. USA 93, 3684–3688.

    Article  PubMed  CAS  Google Scholar 

  • Soto F., Garcia-Guzman M., Karschin C., and Stühmer W. (1996) Cloning and tissue distribution of a novel P2X receptor from rat brain.Biochem. Biophys. Res. Commun. 223, 456–460.

    Article  PubMed  CAS  Google Scholar 

  • Silinsky E. M. and Redman R. S. (1996) Synchronous release of ATP and neurotransmitter within milliseconds of a motor-nerve impulse in the frog.J. Physiol. 492, 815–822.

    PubMed  CAS  Google Scholar 

  • Simon J., Kidd E. J., Smith F. M., Chessell I. P., Murrell-Lagnado R., Humphrey P. P. A., and Barnard E. A. (1997a) Localization and functional expression of splice variants of the P2X2 receptor.Mol. Pharmac. 52, 1–12.

    Google Scholar 

  • Simon J., Webb T. E., and Barnard E. A. (1997b) Distribution of [35S]dATPαS binding sites in the adult rat neuraxis.Neuropharmacology (in press).

  • Simon J., Webb T. E., King B. F., Burnstock G., and Barnard E. A. (1995a) Characterization of a recombinant P2Y purinoceptor.Eur. J. Pharmacol. Mol. Pharmacol. Section 291, 281–289.

    Article  CAS  Google Scholar 

  • Simon J., Webb T. E., and Barnard E. A. (1995b) Characterization of a P2Y purinoceptor in the brain.Pharmacol. Toxicol. 76, 302–307.

    Article  PubMed  CAS  Google Scholar 

  • Southey M. C., Hammet F., Hutchins A. M., Paidhungat M., Somers G. R., and Venter D. J. (1996) Molecular-cloning and sequencing of a novel human P2 nucleotide receptor.Biochim. Biophys. Acta 1309, 77–80.

    PubMed  CAS  Google Scholar 

  • Stam N. J., Klomp J. van de Heuvel M., and Olijve W. (1996) Molecular cloning and characterization of a novel orphan receptor (P2P) expressed in human pancreas that shows high structural homology to the P2U purinoceptor.FEBS. Lett. 384, 260–264.

    Article  PubMed  CAS  Google Scholar 

  • Surprenant A., Buell G. N., and North R. A. (1995) P2X receptors bring new structure to ligand-gated ion channels.Trends Neurosci. 18, 224–229.

    Article  PubMed  CAS  Google Scholar 

  • Surprenant A., Rassendren F., Kawashima E., North R. A., and Buell G. N. (1996) The cytolytic P2Z receptor for extracellular ATP identified as a P2X receptor (P2X7).Science 272, 735–738.

    Article  PubMed  CAS  Google Scholar 

  • Tokuyama Y., Hara M., Jones E. M. C., Fan Z., and Bell G. I. (1995) Cloning of rat and mouse P2Y purinoceptors.Biochem. Biophys. Res. Commun. 211, 211–218.

    Article  PubMed  CAS  Google Scholar 

  • Valera S., Hussy N., Evans R. J., Adami N., North R. A., Surprenant A., and Buell G. N. (1994) A new class of ligand-gated ion channel defined by P2X receptor for extracellular ATP.Nature 371, 516–519.

    Article  PubMed  CAS  Google Scholar 

  • Valera S., Talabot F., Evans R. J., Gos A., Antonarakis S. E., Morris M. A., and Buell G. N. (1995) Characterization anf chromosomal localization of a human P2x receptor from the urinary bladder.Recept. Channels 3, 283–289.

    PubMed  CAS  Google Scholar 

  • Vulchanova, L., Arvidsson U., Riedl M., Wang J., Buell G. N., Surprenant A., North R. A., and Elde R. (1996) Differential distribution of two ATP-gated ion channels (P2X receptors) determined by immunocytochemistry.Proc. Natl. Acad. Sci. USA 93, 8063–8067.

    Article  PubMed  CAS  Google Scholar 

  • Wang C., Namba N., Gonoi T., Inagaki N., and Seino S. (1996a) Cloning and pharmacological characterization of a fourth P2X receptor tissue including various endocrine tissues.Biochem. Biophys. Res. Commun. 230, 187–206.

    Google Scholar 

  • Wang Y., Roman R., Lidofsky S. D., and Fitz J. G. (1996b) Autocrine signaling through ATP release represents a novel mechanism for cell volume regulation.Proc. Natl. Acad. Sci. USA 93, 12,020–12,025.

    CAS  Google Scholar 

  • Webb T. E., Peolde E., Vigne P., Neary J. T., Runberg A., Frelin C., and Barnard E. A. (1996a) The P2Y purinoceptor in rat brain microvascular endothelial cells couples to inhibition of adenylate cyclase.Br. J. Pharmacol.,119, 1385–1392.

    PubMed  CAS  Google Scholar 

  • Webb T. E., Henderson D., King B. F., Wang S., Simon J., Bateson A. N., Burnstock G., and Barnard E. A. (1996b) A novel G protein-coupled P2 purinoceptor (P2Y3) activated preferentially by nucleoside diphosphates.Mol. Pharmacol. 50, 258–265.

    PubMed  CAS  Google Scholar 

  • Webb T. E., Kaplan M. H., and Barnard E. A. (1996c) Identification of 6H1 as a fifth P2Y purinoceptor: p2y5.Biochem. Biophys. Res. Commun. 219, 105–110.

    Article  PubMed  CAS  Google Scholar 

  • Webb T. E., Simon J., and Barnard E. A. (1997) Regional distribution of [35S]2′-deoxy 5′-o-(1-thio) ATP binding sites and the P2Y1 mRNA within the chick brain.Neuroscience, in press.

  • Webb T. E., Simon J., Bateson A. N., and Barnard E. A. (1994) Transient expression of the recombinant chick brain P2Y1 purinoceptor and localization of the corresponding mRNA.Cell. Mol. Biol. 40, 437–442.

    PubMed  CAS  Google Scholar 

  • Webb T. E., Simon J., Krishek B. J., Bateson A. N., Smart T. G., King B. F., Burnstock G., and Barnard E. A. (1993) Cloning and functional expression of a brain G-protein-coupled ATP receptor.FEBS Lett. 324, 219–225.

    Article  PubMed  CAS  Google Scholar 

  • Welford L. A., Cusack N. J., and Hourani S. M. O. (1987) The structure-activity relationships of ectonucleotidases and of excitatory P2 purinoceptors: evidence that dephosphorylation of ATP analogues reduces pharmacological potency.Eur. J. Pharmacol.,141, 123–130.

    Article  PubMed  CAS  Google Scholar 

  • Werner P., Seward E. P., Buell G. N., and North R. A. (1996) Domains of P2X receptors involved in desensitization.Proc. Natl. Acad. Sci. USA 93, 15,485–15,490.

    CAS  Google Scholar 

  • Wierasko A. and Ehrlich Y. H. (1994) On the role of extracellular ATP in the induction of long-term protentiation in the hippocampus.J. Neurochem. 63, 1731–1737.

    Article  Google Scholar 

  • Yokomizo T., Izumi T., Chang K., Takuwa Y., and Shimizu T. (1997) A G protein-coupled receptor for leukotriene B4 that mediates chemotaxis.Nature 387, 620–624.

    Article  PubMed  CAS  Google Scholar 

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  1. Molecular Neurobiology Unit, Royal Free Hospital School of Medicine, Rowland Hill Street, NW3 2PF, London, UK

    Eric A. Barnard, Joseph Simon & Tania E. Webb

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  1. Eric A. Barnard
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Barnard, E.A., Simon, J. & Webb, T.E. Nucleotide receptors in the nervous system. Mol Neurobiol 15, 103–129 (1997). https://doi.org/10.1007/BF02740631

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