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Molecular mechanism of anesthesia of xenon : specific or nonspecific effect?

Research Project

Project/Area Number 10470317
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Anesthesiology/Resuscitation studies
Research InstitutionOsaka University

Principal Investigator

MASHIMO Takashi  Osaka University Graduate School of Medicine, Professor, 医学系研究科, 教授 (60157188)

Co-Investigator(Kenkyū-buntansha) HAMANAKA Toshiaki  Osaka University Graduate School of Engineering Science, Assistant Professor, 基研工学研究科, 助手
UCHIDA Ichiro  Osaka University Graduate School of Medicine, Lecturer, 医学系研究科, 講師 (00232843)
NISHIMURA Shinya  Osaka University Hospital, Assistant Professor, 医学部・附属病院, 助手 (00263286)
YOSHIYA Ikuto  Osaka University Hospital, Professor, 医学部・附属病院, 教授 (80028505)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,400,000 (Direct Cost: ¥12,400,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1998: ¥5,700,000 (Direct Cost: ¥5,700,000)
Keywordsanesthetic action / mechanism / specific / non specific / xenon / nitrous oxide / GABA_A recptor / NMDA receptor / キセノン / イソフルラン / セボフルラン / 揮発性麻酔薬 / 重水 / イソフルレン / MAC
Research Abstract

1) Binding of volatile anesthetics to purple membranes studied by X-ray diffraction.
The concentrated purple membranes suspension was sealed in a 1 mm diameter glass capillary which also included buffer solution with or without volatile anesthetic, diiodomethane at its both sides. The X-ray diffraction pattern was recorded on a imaging plate and read by an image scanner. The X-ray diffraction study showed that anesthetics bound specifically to the protein-lipid interfacial region within a trimer near the surface of bacteriorhodopsin in the purple membrane.
2) Effects of xenon, nitrous oxide and volatile anesthetics on recombinant GABA_A receptors and recombinant NMDA receptors expressing in Xenopusoocyte.
Mouse cDNAs encoding for α1, β2 and γ2s GABA_A receptor subunits, and for ζ1, ε1 NMDA receptor were subcloned into transcription vector. A vector containing each subunit was linearized by an appropriate restriction enzyme to create the template cDNA and cRNA was synthesized in vitro. Different combinations of GABA_A receptor subunits (α1 β2 and α1 β2 γ2s ) and NMDA receptor (ζ1 ε1) were injected to Xenopusoocyte followed by incubation at 20℃ for >48h. The electrophysiological recordings were made by using the two electrode-voltage clamp technique. Volatile anesthetics potentiated GABA-induced current in dose dependent manners in the α1 β2 and α1 β2 γ2s receptors, but xenon and nitrous oxide showed no significant potentiation. On the contrary, volatile anesthetics did not affect NMDA-induced current in the ζ1 ε1 recentor, but xenon and nitrous oxide depressed it dose-dependently.
The results suggest that an inert gas, xenon acts on neuronal receptors in the specific manner.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] Hamanaka T, et al.: "Binding of volatile anesthetics to purple membranes studied by X2 ray diffraction"Toxicology Letters. 100-101. 397-403 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fukami S, et al.: "The effects of a point mutation of the β_2 : subunit GABA_A receptor on direct and modulatory actions of general anesthetics."Eur J Pharmacol. 368. 269-270 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] "The quantitative analysis of three action modes of volatile anesthetics on purple membrnae."Biochim Biophys Acta. 1467. 139-149 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hamanaka T, Nakagawa T, kito Y, Nishimura S, Uchida I, Mashimo T: "Binding of volatile anesthetics to purple membranes studied by X-ray diffraction."Toxicology Letters. 100-101. 397-403 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fukami S, Uchida I, Takenoshita M, Mashimo T, Yoshiya I: "The effects of a point mutation of the β_2 subunit GABA_A receptor on direct and modulatory actions of general anesthetics."Eur J Pharmacol. 368. 269-276 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakagawa T, Hamanaka T, Nishimura S, Uchida I, Mashimo T, Kito Y: "The quantitative analysis of three action modes of volatile anesthetics on purple membmae."Biochim Biophys Acta. 1467. 139-149 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fukami S,Uchidal,Takenoshita M,Mashimo T,Yoshiyal: "The effects of a point mutation of the β_2 Subunit GABA_A receptor on direct and modulatory actions of general anesthetics."Eur J Pharmacol. 368. 269-276 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nakagawa T,Hamanaka T,Nishimura S Uchidal,Mashimo T,Kito Y: "The quantitative analysis of three action modes of volatile anesthetics on purple membrnae."Biochim Biophys Acta. 1467. 139-149 (2000)

    • Related Report
      2000 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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