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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)
上野 伸哉  国立医薬品食品衛生研究所, 薬理部, 研究員
Project Period (FY) 1996 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥7,400,000 (Direct Cost: ¥7,400,000)
Fiscal Year 1998: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1996: ¥2,300,000 (Direct Cost: ¥2,300,000)
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.

Report

(4 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • 1996 Annual Research Report
  • Research Products

    (49 results)

All Other

All Publications (49 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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K. Inoue et al.: "RECIPROCAL REGULATION BY ZINC ION OF ATP-RECEPTORS."Hokkaido University Press. 394(133-142) (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [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
    • Related Report
      1998 Final Research Report Summary
  • [Publications] K.Inoue et al.: "ATP stimulates Ca2+-dependent plasminogen release from cultured microglia." Br.J.Pharmacol.123. 1304-1310 (1998)

    • Related Report
      1998 Annual Research Report
  • [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)

    • Related Report
      1998 Annual Research Report
  • [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)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Koizumi1 and K.Inoue: "Functional coupling of secretion and capacitative calcium entry in PC12 cells." BBRC. 244. 293-297 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Ueno et al.: "Characterization of Ca2+ influx through recombinant P2X receptor in C6BU-1" Br.J.Pharmacol.124. 1484-1490 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] S.Ueno et al.: "Cell type-specific ATP-activated responses in rat dorsal root ganglion neurons." Br.J.Pharmacol.126. 429-436 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Inoue et al.: "RECIPROCAL REGULATION BY ZINC ION OF ATP-RECEPTORS." Hokkaido University Press, 394(133-142) (1998)

    • Related Report
      1998 Annual Research Report
  • [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)

    • Related Report
      1998 Annual Research Report
  • [Publications] K.Nakazawa, et al.: "Potent inhibition by trivalent cations of ATP-gated channels." Eur J Pharmacol. 325. 237-243 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H.Uneyama, et al.: "Blockade by cilnidipine(FRC-8653)of N-type Ca2+ current in acutely dissociated rat sympathetic neurones." Br.J.Pharmacol.122. 37-42 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Koizumi and K.Inoue.: "Inhibition by ATP of calcium oscillations in cultured rat hippocampal neurons." Br.J.Pharmacol.122. 51-58 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Nakazawa, et al.: "Voltage-dependent gating of ATP-activated channels in PC12 cells." J.Neurophysiol.78. 884-890 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Nakazawa, et al.: "pH dependence of facilitation by neurotransmitters and divalent cations of P2X2 purinoceptor/channels." Eur J Pharmacol. 337. 309-314 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Inoue et, al.: "ATP stimulates Ca2+-dependent plasminogen release from cultured microglia." Br.J.Pharmacol.(印刷中).

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Inoue and S.Koizumi.: "ATP receptors in psychosis.in Ca ion modulators" ハ-ウッドアカデミック出版社(印刷中), (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Nakazawa, et al.: "Selective inhibition by fluspirilene and pimozide of L-type Ca2+ channels." ハ-ウッドアカデミック出版社(印刷中), (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Ikeda et al.: "Potentiation by cadmium ion of ATP-evoked dopamine release in rat phaeochromocytoma cells." Br.J.Pharmacol.117. 950-954 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Ito et al.: "Inhibition by antipsychotic drugs of ionic current through L-type Ca2+ channels in PC12 cells." Eur.J.Pharmacol.314. 143-150 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Inoue et al.: "Implication of ATP receptors in brain functions." Progress in Neurobiology. 50. 483-492 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 井上和秀: "脳における情報伝達" 蛋白質・核酸・酵素, 412 (1997)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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