| Project/Area Number |
16K11740
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Surgical dentistry
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
木村 幸文 北海道大学, 大学病院, 講師 (00292037)
長谷 由理 北海道大学, 大学病院, 助教 (20626121)
藤澤 俊明 北海道大学, 歯学研究院, 教授 (30190028)
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| Project Period (FY) |
2016-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | 揮発性麻酔薬 / 静脈麻酔薬 / NMR（核磁気共鳴）スペクトル / 生体膜モデル / リポソーム / Na,K-ATPase / Mg-ATPase / バルビツール酸系薬物 / VOCセンサー / 全身麻酔薬 / 作用機序 / 核磁気共鳴 / 生体モデル膜 / NMR |
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| Outline of Final Research Achievements |
We investigated the effect of desflurane，sevoflurane and isoflurane on intracerebral Na,K-ATPase, which is related to maintain excitability of nerve cells, to elucidate the reaction mechanism of inhalational anesthetics. We found that inhalational anesthetics inhibited Na,K-ATPase activity as intravenous anesthetics did, suggesting that inhibition of Na,K-ATPase activity is related to the various pharmacological effects of general anesthetics. We also found that inhalational anesthetics are present in the outer surface of liposome as model of biomembrane and do not enter inside the liposome by 19F-NMR study, suggesting that the effects of general anesthetics on membrane fluidity are caused by interaction with surface of membrane.
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| Academic Significance and Societal Importance of the Research Achievements |
膨大な研究の蓄積があるのに全身麻酔薬の作用機構は不明な点が多い．本研究において，脳内で重要な機能に関与するNa,K-ATPaseとMg-ATPase活性を揮発性麻酔薬及び静脈麻酔薬が抑制することを明らかにした．また，申請者がESR(電子スピン共鳴)法により報告した「全身麻酔薬は生体膜の表層で作用する」という仮説を，NMR(核磁気共鳴)を用いた研究により確認した．物理・化学的な測定法と生物学的な解析を融合した申請者の研究手法は，今後の全身麻酔薬の作用機構の研究において新たな視点を提供した．
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