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1998 Fiscal Year Final Research Report Summary

A neuropharmacological Research for the Function of ATP Receptors in the Nociception

Research Project

Project/Area Number 08457416
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionNATIONAL INSTITUTE OF HEALTH SCIENCES

Principal Investigator

INOUE Kazuhide  National Institute of Health Sciences, Section Chief, 薬理部, 室長 (80124379)

Co-Investigator(Kenkyū-buntansha) UENO Shinya  National Institute of Health Sciences, Researcher, 薬理部, 研究員
KOIZUMI Schuichi  National Institute of Health Sciences, Researcher, 薬理部, 研究員 (10280752)
Project Period (FY) 1996 – 1998
KeywordsATP RECEPTORS / PAIN / DORSAL ROOT GANGLION NEURON / ELECTROPHYSIOLOGY / INTRACELLULAR CALCIUM / C-FIBER
Research Abstract

The aim of our study is to clarify the relationship between expression pattern of P2X receptors and the cell type of rat dorsal root ganglion (DRG) neurons. We identified the nociceptive cells of acutely dissociated DFG neurons from adult rats type using capsaicin sensitivity. Two types of ATP-activated currents, one with fast, the other with slow desensitization, were found under voltage-clamp conditions. In addition, cells with fast but not slow desensitization responded to capsaicin, indicating that there was a mutual relevance between current kinetics and capsaicin-sensitivity. Both types of neurons were responsive to ATP and α,β-methylene-ATP (α,βmeATP). The concentration of α,βmeATP producing half-maximal activation (EC50) of neurons with fast desensitization was less (11 μM) than that of neurons with slow desensitization (63 μM) , while the Hill coefficients were similar. Suramin and pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid tetrasodium (PPADS) antagonized α,βmeATP-induced currents in both types of neurons. At the RNA level, small cells of the DRG predominantly expressed mRNAs of P2X3 and medium-sized cells expressed FNAs of P2X2 and P2X3. In contrast, both of mRNAs were not detected in large cells of the DRG. These results suggested that capsaicin-sensitive, small-sized DRG neurons expressed mainly the homomeric P2X3 subunit and that capsaicin-insensitive, medium-sized DRG neurons expressed the heteromultimeric receptor with P2X2 and P2X3.

  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] K. Inoue et al.: "ATP stimulates Ca2+-dependent plasminogen release from cultured microglia"Br. J. Pharmacol. 123. 1304-1310 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S. Koizumi et al.: "A secreted form of b-amyloid-precursor protein stimulates intracellular Ca2+increase in cultured rat hippocampal neurones"Br. J. Pharmacol. 123. 1483-1489 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Wirkner et al.: "Differential age-deoendent expression of a2 adrenoceptor- and P2 purinoceptor-functions in rat locus coeruleus neurons"Naunyn-Schmiedeberg's Arch. Pharmacol. 357. 186-189 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S. Koizumi1 and K. Inoue: "Functional coupling of secretion and capacitative calcium entry in PC12 cells"BBRC. 244. 293-297 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S. Ueno et al.: "Characterization of Ca2+ influx through recombinant P2X receptor in C6BU-1"Br. J. Pharmacol.. 124. 1484-1490 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] S. Ueno et al.: "Cell type-specific ATP-activated responses in rat dorsal root ganglion neurons"Br. J. Pharmacol. 126. 429-436 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] K. Inoue et al.: "RECIPROCAL REGULATION BY ZINC ION OF ATP-RECEPTORS."Hokkaido University Press. 394(133-142) (1998)

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      「研究成果報告書概要(和文)」より
  • [Publications] 井上和秀: "ATP受容体と脳機能障害"九州大学出版会. 615(115-123) (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] M.Ikeda, S.Koizumi, K.Nakazawa, K.Inoue. K.Ito and K.Inoue: "Potentiation by cadmium ion of ATP-evoked dopamine release in rat phaeochromocytoma cells"Br.J.Pharmacol.. 117. 950-954 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Ito, K.Nakazawa, S.Koizumi, K.Takeuchi, T.Hashimoto, Y.Ohno and K.Inoue: "Inhibition by antipsychotic drugs of ionic current through L=type Ca2+ channels in PC12 cells"Eur.J.Pharmacol.. 314. 143-150 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Inoue, K.Nakazawa, K.Inoue, K.Fujimori , Y_Ohno, A.Takanaka, H.Itagaki, S.Kato, T.Kobayashi and Y.Kuroiwa: "Evaluation of stinging-inducing chemicals using cultured neuronal cells : an electrophysiological approach"Toxicol in vitro. 10. 455-462 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Nakazawa M.Liu K.Inoue and Y. Ono: "Potent inhibition by trivalent cations of ATP-gated channels"Eur J Pharmacol. 325. 237-243 (1997)

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      「研究成果報告書概要(欧文)」より
  • [Publications] H.Uneyama, A.Takahara, H.Uchida, R.Yoshimoto, K.Inoue and N.Akaike: "Blockade by cilnidipine (FRC-8653) of N-type Ca2+ current in acutely dissociated rat sympathetic neurons"Br.J.Pharmacol.. 122. 37-42 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Koizumi and K.Inoue: "Inhibition by ATP of calcium oscillations in cultured rat hippocampal neurons"Br.J.Pharmacol. 122. 51-58 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Nakazawa, M.Liu, K.Inoue and Y.Ono: "Voltage-dependent gating of ATP-activated channels in PC12 cells"J Neurophysiol. 78. 884-890 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Nakazawa, M.Liu, K.Inoue and Y.Ono: "pH dependence of facilitation by nevrotransmitters and divalent cations of P2X2 purinoceptor/channels"Eur.J.Pharmacol.. 337. 309-314 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Liu, K.Nakazawa, K.Inoue and Y.Ono.: "Potent and voltage-dependent block by philanthotoxin-343 of mammalian neuronal nicotinic receptor/channels."Br. J. Pharmacol.. 122. 379-385 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K. Inoue, K. Nakajima, T. Morimoto, Y. Kikuchi, S.Koizumi, P. Illes and S.Kohsaka: "ATP stimulates Ca2+-dependent plasminogen release from cultured microglia."Br.J.Pharmacol.. 123. 1304-1310 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Koizumi, M.Ishiguro, I.Ohsawa. T. Morimoto, C. Takamura, K. Inoue and S. Kohsaka: "A secreted form of b-amyioid-precursor protein stimulates intracellular Ca2+ increase in cultured rat hippocampal neurons"Br.J.Pharmacol. 123. 1483-1489 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Wirkner, H.Franke, K.Inoue and P.llles: "Differential age-deoendent expression of a2 adrenoceptor- and P2 purinoceptor-functions in rat locus coeruleus neurons"Naunyn- Schmiedeberg's Arch. Pharmacol.. 357. 186-189 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Uneyama, H.Uchida, R.Yoshimoto, S.Ueno, K.Inoue and N.Akaike: "Effects of a novel antihypertensive drug, cilnidipine, on the catecholamine secretion from the differentiated PCi2 cells"Hypertension. 31. 1195-1199 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S. Koizumi1 and K. Inoue: "Functional coupling of secretion and capacitative calcium entry in PC12 cells"BBRC. 244. 293-297 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Koizumi, H. Uneyama, M. Ikeda, S. Ueno and K. Inoue: "Inhibition by imipramine of ATP-evoked responses in rat pheochromocytoma cells"BBRC. 244. 342-346 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Nakazawa, Y.Ohno and K.Inoue: "An aspartic acid residue near the second transmembrane segment of ATP receptor/channel regulates agonist sensitivity"BBRC. 244. 599-603 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Nakazawa, K.Inoue and Y.Ohno: "An asparagine residue regulating conductance through P2X2 receptor/channels"Eur.J.Pharmacol.. 347. 141-144 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] S.Ueno, S.Koizumi and K.Inoue: "Characterization of Ca2+ influx through recombinant P2X receptor in C6BU-1"Br.J.Pharmacol.. 124. 1484-1490 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] W.Poelchen D Sieler K.Inoue and P.Illes: "Effect of extracellular adenosine 5'-triphosphate on principal neurons of the rat ventral tegmental area"Brain Res. 800. 170-173 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] M.Yamamoto, T.Kawanishi, T.Kiuchi, M.Ohta, I.Yokota, H.Ohata, K_Momose, K.Inoue, and T.Hayakawa: "Discrepant Intracellular pH Changes Following Intracellular Ca2+ Increases Induced by Glutamate and Ca2+ Ionophores in Rat Hippocampal Neurons"Life Sci.. 63. 55-63 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] K.Shibata, M.Ikuko, K.Inoue and T.Katsuragi: "Muscarinic acetylcholine receptor-mediated increase of angiotensin type 2 receptor mRNA in PC12 cells"NeuroReport. 9. 3783-3789 (1998)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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