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Neuronal and behavioral research on the function of ATP receptors in the signal trasnduction of pain.

Research Project

Project/Area Number 11557115
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section展開研究
Research Field Anesthesiology/Resuscitation studies
Research InstitutionNational Institute of Health Sciences (NIHS)

Principal Investigator

INOUE Kazuhide  NIHS BIOSIGNALING DIRECTOR, 代謝生化学部, 部長 (80124379)

Co-Investigator(Kenkyū-buntansha) KOIZUMI Schuichi  NIHS PHARMACOLOGY SECTION CHEAF, 薬理部, 室長 (10280752)
上野 伸哉  福岡大学, 医学部・薬理学教室, 講師 (00312158)
津田 誠  国立医薬品食品衛生研究所, 薬理部, 研究員
Project Period (FY) 1999 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥13,200,000 (Direct Cost: ¥13,200,000)
Fiscal Year 2002: ¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2001: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2000: ¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 1999: ¥3,400,000 (Direct Cost: ¥3,400,000)
KeywordsATP RECEPTOR / P2X / P2Y / NEUROPATHIC PAIN / ALLODYNIA / DRG / C-FIBER / Aδ / 疼痛モデル
Research Abstract

We had found that the stimulation of ATP receptors evoked allodynia as well as nocifensive behavior and hyperthermal algesia. This allodynia is similar to the symptom of neuropathic pain which is resistant to morphine and NSAIDs, anti-pain drugs. To control of this pain is very important in the clinical event, we tried to reveal the mechanism and find the responsible receptor subtype. In the project we found that the both stimulation of ionotropic P2X receptor and G protein-coupled receptor P2Yevoke novel allodynia-like behaviors which are different from each other mentioned below.
The stimulation by α,βmethlene ATP of P2X2+3 heteromeric receptor ( P2X2 and P2X3 compose a heteromeric origomer which is a novel functional receptor/channel.) caused the allodynia which is independent of C-fiber and is continue to 2 hr after the stimulation. On the other, the stimulation of P2Y2 caused C-fiber dependent allodynia which is continue to more than 4 hr after the stimulation. These results indicate that both allodynia are evoked a different mechanism, respectively.

Report

(5 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (44 results)

All Other

All Publications (44 results)

  • [Publications] M.Tsuda, Y.Shigemoto-Mogami, S.Ueno, S.Koizumi, H.Ueda, T.Iwanaga, K.Inoue: "Down-regulation of P2X3 receptor-dependent sensory functions in A/J inbred mouse strain"Eur.J.Neurosci.. 15. 1444-1450 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Tsuda, S.Koizumi, K.Inoue: "Role of endogenous ATP at the incision area in a rat model of postoperative pain"NeuroReport. 12. 1701-1704 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Tsuda, S.Koizumi, A.Kita, Y.Shigemoto, S.Ueno, K.Inoue: "Mechanical allodynia caused by intraplantar injection of P2X receptor agonist in rats : Involvement of the heteromeric P2X2/3 receptor signalling in capsaicin-insensitive primary afferent neurons"J.Neurosci.. 20. RC90(1-5) (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Tsuda, S.Ueno, K.Inoue: "Evidence for the involvement of spinal endogenous ATP and P2X receptors in the nociceptive responses caused by formation and capsaicin in mice"Br.J.Pharmacol.. 128. 1497-1504 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Tsuda, S.Ueno, K.Inoue: "In vivo pathway of thermal hyperalgesia by intrahecal administration of a,b-methylene ATP in mouse spinal cord : Involvement of glutamate-NMDA receptor system"Br.J.Pharamacol.. 127. 449-456 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Ueno, M.Tsuda, T.Iwanaga, K.Inoue: "Cell type-specific ATP-activated responses in rat dorsal root ganglion neurons"Br.J.Pharmacol.. 126. 429-436 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K. Inoue, M. Tsuda, S. Koizumi: "ATP induced three types of pain behaviors including allodynia"Drug Develp Res. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T.Moriyama, T. Iida, K. Kobayashi, T. Higashi, T. Fukuoka, H. Tsumura, C. Leon, N. Suzuki, K. Inoue , C. Gachet, K. Noguchi and M. Tominaga: "Possible involvement of P2Y2 metabotropic receptors in ATP-induced TRPV1-mediated thermal hypersensitivity"Pro.Natl.Acad.Sci.USA,. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Sasaki, M.Hoshi, C.Akazawa, Y.Nakamura, H.Tsuzuki, K.Inoue and S.Kohsaka: "Selective expression of Gi/o-coupled ATP receptor P2Y12 in microglia in rat brain"Glia. in press.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Koizumi, P.Rosa, G. B. Willars, R.A. J. Challiss, E. Taverna, M. Francolini, M. D. Bootman, P. Lipp, K. Inoue, J. Roder and A. Jeromin: "Mechanisms underlying the neuronal calcium sensor-1-evoked enhancement of exocytosis in PC12 cells"J. Biol. Chem.. 277. 30315-30324 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] K.Inoue, S.Koizumi, S.Fuziwara, S.Denda, K.Inoue and M.Denda: "Functional vanilloid receptors in cultured normal human epidermal keratinocytes"BBRC. 291. 124-129 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Tsuda, Y.Shigemoto-Mogami, S.Ueno, S.Koizumi, H.Ueda, T.Iwanaga and K.Inoue: "Down-regulation of P2X3 receptor-dependent sensory functions in A/J inbred mouse strain"Eur.J.Neurosci. 15. 1444-1450 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y.Shigemoto-Mogami, S.Koizumi, M. Tsuda, K.Ohsawa, S.Kohsaka and K.Inoue: "Mechanisms underlying extracellular ATP-evoked IL-6 release in mouse microglial cell line"MG-5. J.Neurochem.. 78. 1339-1349 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Tsuda, S.Koizumi and K.Inoue: "Role of endogenous ATP at the incision area in a rat model of postoperative pain"NeuroReport. 12. 1701-1704 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Honda, Y.Imai, K.Ohsawa, Y.Nakamura, K.Inoue and S.Kohsaka: "Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors"J.Neurosci.. 21. 1975-1982 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Tsuda, S.Koizumi, A.Kita, Y.Shigemoto, S.Ueno and K.Inoue: "Mechanical allodynia caused by intraplantar injection of P2X receptor agonist in rats : Involvement of the heteromeric P2X2/3 receptor signalling in capsaicin-insensitive primary afferent neurons"J.Neurosci.. 20. RC90(1)-(5) (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] I.Hide, M.Tanaka, A.Inoue, K.Inoue, K.Nakajima, S.Kohsaka and Y.Nakata: "Extracellular ATP triggers TNF-a release from rat microglia"J.Neurochem.. 75. 965-972 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] A.Tomioka, S.Ueno, K.Kohama, F.Goto, K.Inoue: "Propofol potentiates ATP-activated currents on recombinant P2X4 receptor channels expressed in human embryonic kidney 293 cells"Neurosci Lett.. 284. 167-170 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] J.S.Rhee, Z.M.Wang, J.Nabekura, K.Inoue and N.Akaike: "ATP facilitates spontanoeous glycinergic IPSC frequency at dissociated dorsal horn interneurone synapses"J.Physiol.(Lond.). 524. 471-483 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Tsuda, S.Ueno and K.Inoue: "Evidence for the involvement of spinal endogenous ATP and P2X receptors in the nociceptive responses caused by formalin and capsaicin in mice"Br.J.Pharmacol.. 128. 1497-1504 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Tsuda, S.Ueno and K.Inoue: "In vivo pathway of thermal hyperalgesia by intrathecal administration of a,b-methylene ATP in mouse spinal cord : Involvement of glutamate-NMDA receptor system"Br.J.Pharmacol.. 127. 449-456 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] S.Ueno, M.Tsuda, T.Iwanaga and K.Inoue: "Cell type-specific ATP-activated responses in rat dorsal root ganglion neurons"Br.J.Pharmacol.. 126. 429-436 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M.Tsuda, Y.Shigemoto-Mogami, S.Ueno, S.Koizumi, H.Ueda, T.Iwanaga, K.Inoue: "Down-regulation of P2X3 receptor-dependent sensory functions in A/J inbred mouse strain"Eur. J. Neurosci.. 15. 1444-1450 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] K.Inoue, S.Koizumi, S.Fuziwara, S.Denda, K.Inoue, M.Denda: "Functional vanilloid receptors in cultured normal human epidermal keratinocytes"BBRC. 291. 124-129 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Koizumi, P.Rosa, G.B.Willars, R.A.J.Challiss, E.Taverna, M.Francolini 2, M.D.Bootman, P.Lipp, K.Inoue, J.Roder, A.Jeromin: "Mechanisms underlying the neuronal calcium sensor-1-evoked enhancement of exocytosis in PC12 cells"J. Biol. Chem.. 277. 30315-30324 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] H.Aihara, S.Fujiwara, I.mizuta, H.Tada, T.Kanno, H.Tozaki, K.Nagai, Y.Yajima, K.Inoue, T.Kondoh, Y.Motooka, T.Nishizaki: "Adenosine triphosphate accelerates recovery from hypoxic/hypoglycemic pertuibation of guinea pig hippocampal neurotransmission via a P2 receptor"Brain Research. 952. 31-37 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Koiznmi S, Saito Y, Nakazawa K, Nakajima K, Sawada JI, Kohsaka S, Illes P, Inoue K: "Spatial and temporal aspects of Ca2+ signaling mediated by P2Y receptors in cultured rat hippocampal astrocytes"Life Sci.. 72. 431-442 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] S.Honda, Y.Imai, K.ohsawa, Y.Nakamura, K.Inoue, S.Kohsaka: "Extracellular ATP or ADP induce chemotaxis of cultured microglia through Gi/o-coupled P2Y receptors"J. Neurosci.. 21. 1975-1982 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M.Tsuda, S.Koizumi, K.Inoue: "Role of endogenous ATP at the incision area in a rat model of postoperative pain"NeuroReport. 98. 1701-1704 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] K.Inoue, S.Koizumi: "Mechanism of the inhibitory action of ATP in rat hippocampus"Drug Develp Res.. 52. 95-103 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Y.Shigemoto, S.Koizumi, M.Tsuda, K.Ohsawa, S.Kohsaka, K.Inoue: "Mechanisms underlying extracellular ATP-evoked IL-6 release in mouse microglial cell line, MG-5"J. Neurochem.. 78. 1339-1349 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] J.S.Rhee,Z.M.Wang,J.Nabekura,K.Inoue and N .Akaike: "ATP facilitates spontanoeous glycinergic IPSC frequency at dissociated dorsal horn interneurone synapses"J.Physiol.(Lond.). 524. 471-483 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shinoura H,Take H,Hirasawa A,Inoue K,Ohno Y,Hashimoto K,Tsujimoto G: "Key amino acids of vasopressin V1a receptor responsible for the species difference in the affinity of OPC-21268"FEBS Lett.. 466. 255-258 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] A.Tomioka,S.Ueno,K.Kohama,F.Goto,K.Inoue: "Propofol potentiates ATP-activated currents on recombinant P2X4 receptor channels expressed in human embryonic kidney 293 cells"Neurosci Lett.. 284. 167-170 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] I.Hide,M.Tanaka,A.Inoue,K.Inoue,K.Nakajima,S.Kohsaka and Y.Nakata: "Extracellular ATP triggers TNF-α release from rat microglia."J.Neurochem.. 75. 965-972 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] M.Tsuda,S.Koizumi,A.Kita,Y.Shigemoto,S.Ueno and K.Inoue: "Mechanical allodynia caused by intraplantar injection of P2X receptor agonist in rats : Involvement of the heteromeric P2X2/3 receptor signalling in capsaicin-insensitive primary afferent neurons"J.Neurosci.. 20. RC90(1-5) (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Honda,Y.Imai,K.ohsawa,Y.Nakamura,K.Inoue and S.Kohsaka: "Extracellular ATP induces membrane ruffling and random migration in rat primary cultured microglia through Gi/o-coupled P2Y receptor(s)"J.Neurosci. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] S.Ueno,M.Tsuda,T.Iwanaga and K.Inoue: "Cell type-specific ATP-activated responses in rat dorsal root ganglion neurons"Br.J.Pharmacol.. 126. 429-436 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Tsuda,S.Ueno and K.Inoue: "In vivo pathway of thermal hyperalgesia by intrathecal administration of α,β-methylene ATP in mouse spinal cord : Involvement of glutamate-NMDA receptor system"Br.J.Pharmacol.. 127. 449-456 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] K.Nakazawa,K.Inoue and Y.Ohno: "Block and unblock by imipramine of cloned and mutated P2X2 receptor/channel expressed in Xenopus oocytes"Neurosci.Lett.. 264. 93-96 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] M.Tsuda,S.Ueno and K.Inoue: "Evidence for the involvement of spinal endogenous ATP and P2X receptors in the nociceptive responses caused by formalin and capsaicin in mice"Br.J.Pharmacol.. 128. 1497-1504 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] J.S.Rhee,Z.M.Wang,J.Nabekura,K.Inoue and N.Akaike: "ATP facilitates spontanoeous glycinergic IPSC frequency at dissociated dorsal horn interneurone synapses"J.Physiol.(Lond.). (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] A.Tomioka,S.Ueno,K.Kohama,F.Goto,K.Inoue: "Propofol potentiates ATP-activated currents on recombinant P2X4 receptor channels expressed in human embryonic kidney 293 cells"Neurosci.Lett.. (in press). (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Inoue K.,Koizumi S.,Ueno S.,Kita Y.,Tsuda M.: "Nucreotides and their receptors in the nervous system"The function of ATP receptors in the synaptic transmission in the hippocampus. 193-206 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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