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Molecular interaction between general anesthetics and GABAA receptor

Research Project

Project/Area Number 08457407
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

YOSHIYA Ikuto  Osaka University Medical School, Professor, 医学部, 教授 (80028505)

Co-Investigator(Kenkyū-buntansha) UCHIDA Ichiro  Osaka University Medical School, Assistant Professor, 医学部, 助手 (00232843)
NISHIMURA Shinya  Osaka University Medical School, Assistant Professor, 医学部, 助手 (00263286)
TAKENOSHITA Makoto  Osaka University Medical School, Lecturer, 医学部, 講師 (00144486)
MASIMO Takashi  Osaka University Medical School, Associate Professor, 医学部, 助教授 (60157188)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥7,700,000 (Direct Cost: ¥7,700,000)
Fiscal Year 1997: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1996: ¥4,800,000 (Direct Cost: ¥4,800,000)
KeywordsGABA^A receptor / Anesthetic / Subunit / Molecular biology / Mutation / Electrophysiology / GABAA受容体 / 麻酔作用機序 / 全身麻酔薬 / GABA_A受容体
Research Abstract

During the two years period supported this grant, we revealed the following two points by using the molecular biological and electrophysiological methods.
1) By using the chimeric receptor studies between alpha1 and beta3 subunit of GABAA receptor, The site of action of propofol potentiation in GABAA receptor function may be in the long hydrophilic NH2 terminal of alpha1 subunit. The further mutational study of amino residues in alpha1 subunit may be necessary to elucidate the precise site for propofol site.
2) The point mutation of tyrosine to phenylalanine at position 157 in beta2 subunit of GABA receptor drastically decreased the sensitivity to GABA but not anesthetics such as propofol, etomidate and pentobarbital. Also this tyrosine mutation of beta2 subunit had no influence on the modulatory actions of these anesthetics. The result suggested the distinct site of action on the direct action of GABA receptor by GABA and anesthetics and the modulatory action of anesthetics may be not mediated by GABA site.

Report

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

    (29 results)

All Other

All Publications (29 results)

  • [Publications] 内田 一郎: "受容体と全身麻酔薬:主としてGABA受容体に関して" LiSA. 4・2. 106-112 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 内田 一郎: "中枢性GABA A受容体と麻酔" 麻酔. 46・増. S84-S89 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 西村 信哉, 真下 節: "受容体のない薬物作用" 呼吸. 16・4. 564-569 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Fukami, I.Uchida, T.Mashino, H.Takenoshita, I.Yoshiya: "Gamma subunit dependent modulation by nitric oxide(No)in recombinant GABA A receptor." Neuroreport. 9・6(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] I.Uchida, I.Cestari, L.LiJ.Yang: "The role of GABA A receptor α,subunit N-terminal extrucellar domain in propofal potentiation of Cl curvent" Neuropharmacology. (in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 内田 一郎: "プロポフォールの薬理作用" ICUとCCU. 22・4. 225-231 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 真下 節: "専門医のための麻酔科学レビュー'96「麻酔の作用機序」" 総合医学社, 6 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 真下 節: "専門医のための麻酔科学レビュー'97「麻酔の作用機序」" 総合医学社, 7 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] I,Uchida: "Receptor and general anesthetics : GABA_A receptor" Lisa. 4・2. 106-112 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] I,Uchida: "Catral GABA_A receptor and anesthesia" Masui. 46・S. S84-S89 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Nishimura: "Actions of drugs not mediated by receptors" Kokyu. 16・4. 564-569 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Fukami: "Ganma Subunit dependent modulation by NO in recombinant GABA_A receptor" Neuroreport. 9・6 (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] I.Uchida: "The role of GABA_A receptor alpha_1 subunit N-terminal extracellar domain in propofol potentiation of Cl current" Neuropharmacelogy. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] I.Uchida: "Pearmacological actions of propofol" ICU&CCU. (in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Mashimo: Anesbhesia reviews'96 "Mechanisum of Anesthesion". Sougo-Igakusha, (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Mashimo: Anesthesia reviews'97 "Mechanisum of Anesthesion". Sougo-Igakusha, (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 内田一郎: "受容体と全身麻酔薬:主としてGABA受容体に関して" LiSA. 4・2. 106-112 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 内田一郎: "中枢性GABAA受容体と麻酔" 麻酔. 46・増. S84-S89 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 西村信哉, 真下節: "受容体のない薬物作用" 呼吸. 16・4. 564-569 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Fukami, I.Uchida, T,Mashimo, H.Takenoshita, I.Yoshiya: "Gamma subunit dependent modulation by nitric oxide (NO) in recombinant GABAA receptor." Neuroreport. 9・6(in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] I.Uchida, I.Cestavi, L.Li, J.Yang: "The role of GABAA receptor α,subunit N-terminal extracellar domain in propofal potentiation of Cl current" Neuropharmacology. (in press). (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 内田一郎: "プロポフォールの薬理作用" ICUとCCU. 22・4. 225-231 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] 真下節: "専門医のための麻酔科学レビュー'96「麻酔の作用機序」" 総合医学社, 6 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 真下節: "専門医のための麻酔科学レビュー'97「麻酔の作用機序」" 総合医学社, 7 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Ping Zhang: "Cardiovascular Effects of an Ultra-Short-Acting Nitvic Oxide-Releasing compound,Zwifferionic Diamine/No Adduct in Dogs." Circulation. 94,9. 2235-2240 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 真下節: "全身麻酔のメカニズム-全身麻酔薬の作用は特異的か非特異的か" 医学のあゆみ. 177・3. 237-242 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 真下節: "ブタの肝臓移植手術におけるプロポフォールの薬物動態" 麻酔. 45・3. 293-297 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Tetsu Kawaguchi: "Xenon is another laughing gas." Canadian Journal of Anuesthesia. 43・4. 641-642 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 内田一郎: "受容体と全身麻酔薬:主としてGABA受容体に関して" LiSA. 4・2. 106-112 (1997)

    • Related Report
      1996 Annual Research Report

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

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