Reverification of the mechanistic membrane effects of anesthetics : Interactions with biomembrane rafts and specific membrane lipids

麻醉剂机械膜效应的重新验证：与生物膜筏和特定膜脂的相互作用

• 批准号: 20592381
• 负责人: TSUCHIYA Hironori
• 金额: $ 2.83万
• 依托单位: Asahi University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20592381/
• 关键词: 麻酔薬; 作用機序; 生体膜; 相互作用; ラフト; 膜脂質; 膜流動性; 心毒性; 薬物立体構造; 構造特異性; 薬理学的機序; 構造-膜活性相関; 局所麻酔薬; 生体膜相互作用; 膜流動性変化; 脂質組成; 麻酔作用と心毒性; 効果減弱と炎症; 脂質過酸化

Apart from the conventional mechanism in which anesthetics specifically bind to receptors and channels, we reverified the mechanistic hypothesis that anesthetics may interact with biomembranes to exert clinically useful and adverse effects based on the latest structural and functional theory about biomembranes. The relevance of membrane lipid rafts to anesthetics was questionable at least in their effects on raft-like model membranes. However, anesthetics structure-dependently interacted with biomimetic membranes consisting of specific lipids (cholesterol and anionic phospholipids) and their interacting potencies were discriminated even between stereoisomers. These results support the membrane interaction of anesthetics as the mode of action.

除了麻醉剂特异性结合与受体和通道的常规机制外，我们质疑了麻醉药可能与生物膜相互作用的机械假设，以基于关于生物膜的最新结构和功能理论发挥临床有用和不利影响。膜脂筏与麻醉剂的相关性至少在其对筏样模型膜的影响中是值得怀疑的。然而，麻醉剂结构依赖于与由特定脂质（胆固醇和阴离子磷脂）组成的仿生膜相互作用，甚至在立体异构体之间也歧视了它们的相互作用效果。这些结果支持麻醉药作为作用方式的膜相互作用。

项目成果

STRUCTURE-MEMBRANE INTERACTIVITY RELATIONSHIP OF LOCAL ANAESTHETICS ASSOCIATED WITH THEIR STEREOSELECTIVE CARDIOTOXICITY

局麻药的结构-膜相互作用关系及其立体选择性心脏毒性

• 发表时间: 2010
• 作者: Hironori Tsuchiya;Takahiro Ueno;Maki Mizogami;Ko Takakura
• 通讯作者: Ko Takakura

Membrane effect of lidocaine is inhibited by interaction with peroxynitrite

利多卡因的膜效应因与过氧亚硝酸盐的相互作用而受到抑制

• 发表时间: 2008
• 期刊: Journal of Anesthesia Vol.22
• 作者: TAKAHIRO UENO;MAKI MIZOGAMI;KO TAKAKURA;HIRONORI TSUCHIYA
• 通讯作者: HIRONORI TSUCHIYA

Anesthetic and Cardiotoxic Effects in the Light of the Interactions of Local Anesthetics and Membrane Lipids

局麻药与膜脂相互作用的麻醉和心脏毒性作用

• 发表时间: 2008
• 期刊: Journal of the Pharmaceutical Society of Japan Vol.128 (Suppl.2)
• 作者: Takahiro Ueno;Maki Mizogami;Ko Takakura;Hironori Tsuchiya
• 通讯作者: Hironori Tsuchiya

STEREOSTRUCTURE-MEMBRANE INTERACTIVITY RELATIONSHIP OF LOCAL ANAESTHETICS ASSOCIATED WITH THEIR STEREOSELECTIVE CARDIOTOXICITY

局麻药的立体结构-膜相互作用关系及其立体选择性心脏毒性

• 发表时间: 2010
• 作者: Hironori Tsuchiya;Takahiro Ueno;Maki Mizogami;Ko Takakura
• 通讯作者: Ko Takakura

膜脂質との相互作用に基づく選択的/非選択的β_1遮断薬の識別

基于与膜脂相互作用的选择性/非选择性 β_1 阻滞剂的鉴定

• 发表时间: 2010
• 作者: Taguchi Y;Hayashi-Sakai S;Iizawa F;Numa-Kinjoh N;溝上真樹,東康加,家始聡介,高倉康,土屋博紀
• 通讯作者: 溝上真樹,東康加,家始聡介,高倉康,土屋博紀