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Investigation of mechanism of central nervous system disorder due to chlorinated

Research Project

Project/Area Number 12470085
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Hygiene
Research InstitutionYamaguchi University

Principal Investigator

HOBARA Tatsuya  Yamaguchi University School of Medicine, Professor, 医学部, 教授 (10116501)

Co-Investigator(Kenkyū-buntansha) KUNITSUGU Ichiro  Yamaguchi University School of Medicine, Research associate, 医学部, 助手 (80314798)
OKUDA Masayuki  Yamaguchi University School of Medicine, Associate Professor, 医学部, 助教授 (50274171)
SHINODA Koh  Yamaguchi University School of Medicine, Professor, 医学部, 教授 (40192108)
Project Period (FY) 2000 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥11,900,000 (Direct Cost: ¥11,900,000)
Fiscal Year 2002: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2001: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2000: ¥10,900,000 (Direct Cost: ¥10,900,000)
Keywordsintracellular calcium / trchloroethylene / trichloroethane / Fluo-3 / bromopropane / neuron / rat / caffeine / カルシウムチャンネル / 細胞内カルシウムイオン / パッチクランプ / 血管平滑筋 / 脊髄後根神経節細胞 / 有機溶剤 / ヘキサン / Fura-2
Research Abstract

Calcium ion in neurons plays an important role in development of action potential, release of neurotransmitter and intracellular signaling with synapse formation and physiological functions. Intracellular calcium ion is derived from either influx from the extracellular fluid through the membrane calcium channels o* release out of the intracellular calcium store sites. Organic solvents used in the field of manufacturing and service industry cause clinical symptoms related to depression of central nervous system function.
We have dissociated dorsal root ganglion neurons from neonatal rat to measure the voltage-dependent calcium current in a whole cell mode of the patch clump. Trichloroethane and trichloroethyene decreased the calcium current. And intervals of the action potential in the current clump mode were shortened. We also found the involvement of other voltage-gated cation channels. Next we investigated the change of intracellular calcium ion concentration released from the intracelular calcium stores with a fluo-indicator Fluo-3. We used in this experiments caffeine which modifies ryanodine receptor of intracellular calcium store, and ATP which stimulates the nucleotide receptor of the DRG neurons. Caffeine induced the increasing of the intracellular calcium level, and trichloroethylene inhibited the increasing. The rise of the intracellular calcium level was also impaired with 1-bromopropane and 2-bromopropane. We also studied aortic smooth muscle and got the same results. These studies suggested that some of organic solvents could act on both the plasma membrane of the neurons and cytoplasmic organelles in entering though the plasma membrane and finally modify the action potential and neurotransmitter release.

Report

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

    (22 results)

All Other

All Publications (22 results)

  • [Publications] M Okuda, I Kunitsugu, S Kobayakawa, T Hobara: "Inhibitory effect of 1,1,1-trichloroethane on calcium channels of neurons"The journal of Toxicological Science. 26:. 169-176 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M Okuda, I Kunitsugu, S Kobayakawa, T Hobara: "Effect of 1,1,1-trichloroethane on calcium current of rat dorsal root ganglion neurons"Bulletin of Environmental Contamination and Toxicology. 67. 476-482 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] I Kunitsugu, M Okuda, S Kobayakawa, Y Wakamoto, T Hobara: "Effects of trichloroethylene on contraction of aortic smooth muscle of rats"Toxicology. 164. 163 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M Okuda, I Kunitsugu, S Kobayakawa, T Hobara: "Effect of n-hexane on uterus smooth muscle contraction"Toxicology. 164. 160 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T Hobara, M Okuda, M Gotoh, K Oki, H Segawa, I Kunitsugu: "Tree cases of thinner-sniffing and estimating the fatal concentration of toluene by toxicokinetics"Promblems of Forensic Sciences. special issue. 105-111 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T Hobara, T Aramaki, M Okuda, M Gotoh, I Kunitsugu, C Yamada: "Effects of alcohol intake on mineral distribution in rats and on serum mineral levels in human"Metal Ions in Biology and Medicine. 6. 550-553 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M Okuda, I Kunitsugu, S Kobayakawa, T Hobara: "Inhibitory effect of 1, 1, 1-trichloroethane on calcium channels of neurons"The journal of Toxicological Science. 26. 169-176 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M Okuda, I Kunitsugu, S Kobayakawa, T Hobara: "Effect of 1, 1, 1-trichloroethane on calcium current of rat dorsal root ganglion neurons"Bulletin of Environmental Contamination and Toxicology. 67. 476-482 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] I Kunitsugu, M Okuda, S Kobayakawa, Y Wakamoto, T Hobara: "Effects of trichloroethylene on contraction of aortic smooth muscle of rats"Toxicology. 164. 163 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] M Okuda, I Kunitsugu, S Kobayakawa, T Hobara: "Effect of n-hexane on uterus smooth muscle contraction"Toxicology. 164. 160 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T Hobara, M Okuda, M Gotoh, K Oki, H Segawa, I Kunitsugu: "Tree cases of thinner-sniffing and estimating the fatal concentration of toluene by toxicokinetics"Problems of Forensic Sciences. Special Issue. 105-111 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] T Hobara, T Aramaki, M Okuda, M Gotoh, I Kunitsugu, C Yamada: "Effects of alcohol intake on mineral distribution in rats and on serum mineral levels in human"Metal Ions in Biology and Medicine. 6. 550-553 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] 奥田昌之, 國次一郎, 小早川節, 杉山真一, 芳原達也: "初代培養精原細胞コメットアッセイを用いた2-ブロモプロパンの毒性評価"産業衛生学雑誌. 44・増刊. 792 (2000)

    • Related Report
      2002 Annual Research Report
  • [Publications] 國次一郎, 奥田昌之, 若本ゆかり, 杉山真一, 小早川節, 芳原: "初代培養精原細胞におけるComet Assayを用いたn-Hexaneの毒性評価"産業衛生学雑誌. 44・増刊. 791 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] M Okuda: "Inhibitory effect of 1,1,1-trichloroethane on calcium channels of neurons"The journal of Toxicological Science. 26:. 169-176 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M Okuda: "Effect of 1,1,1-trichloroethane on calcium current ot rat dorsal root ganglion neurons"Bulletin of Environmental Contamination and Toxicology. 67. 476-482 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] I Kunitsugu: "Effects of trichloroethylene on contraction of aortic smooth muscle of rats"Toxicology. 164. 163 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] M Okuda: "Effect of n-hexane on uterus smooth muscle contraction"Toxicology. 164. 160 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] T Hobara: "Long term health effects on the drinking water containing tetrachloroethylene in humans"Toxicology. 164. 160 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hobara,T. et.al: "Application of a metal-chelating protein, phosvitin to the establishment of safe food system."METAL IONS IN BIOLOGY AND MEDICINE. 6. 544-546 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hobara,T. et.al: "Effects of alcohol intake on mineral distribution in rats and on serum mineral levels in human."METAL IONS IN BIOLOGY AND MEDICINE,. 6. 550-553 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Hobara,T. et.al: "THREE CASES OF THINNER-SNIFFING AND ESTIMATING THE FATAL CONCENTRATION OF TOLUENE BY TOXICOKINETICS."PROBLEMS OF FORENSIC SCIENCES. 105-111 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 2000-04-01   Modified: 2020-11-26  

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