The effect of aging on the sesitiuity of anesthetics in GABAA receptor

衰老对GABAA受体麻醉药敏感性的影响

• 批准号: 09671559
• 负责人: UCHIDA Ichiro
• 金额: $ 1.98万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671559/
• 关键词: anesthetic; GABAA receptor; clone; subunit; molecular biology; electrophysiology; GABAA受容体; 揮発性麻酔薬; 加齢; パッチクランプ; 再構成系; 卵母細胞; GABA_A受容体

The γ-aminobutyric acid type A receptor (GABAィイD2AィエD2 receptor) is a major inhibitory receptor in the central nervous system and has attracted lots of interest as an important site of action of general anesthetics. General anesthetics including volatile and intravenous agents enhance the action of GABA at GABAィイD2AィエD2 receptors and that is regarded as the primary role for inducing the clinical anesthetic state. In this project we revealed the extracellar amino-terminal domain of the α subunit is necessary for the modulatory action of propofol in the recombinant GABAィイD2AィエD2 receptor by using the chimeric subunits technique. Also the studies of the point mutation in β2 subunit suggest that unique loci distinct from pentobarbital and etomidate may exist for the direct action of propofol and that GABA binding site may not mediate the modulatory actions of general anesthetics at GABAィイD2AィエD2 receptors. We are undergoing the further project to elucidate the site-of-action for the local anesthetics in the recombinat GABAィイD2AィエD2 receptors.

γ-氨基丁酸A型受体（γ-aminobutyric acid type A receptor，GABA受体D2 A受体D2 receptor）是中枢神经系统的主要抑制性受体，是全身麻醉药的重要作用部位。全身麻醉药包括挥发性和静脉内麻醉剂，可增强GABA对GABA受体D2 A的作用，这被认为是诱导临床麻醉状态的主要作用。本课题利用嵌合亚基技术揭示了重组GABA受体α亚基的胞外氨基端结构域是丙泊酚调节GABA受体α亚基D2 A亚基D2受体活性所必需的。β2亚单位点突变的研究提示，异丙酚的直接作用可能存在不同于戊巴比妥和依托咪酯的独特位点，GABA结合位点可能不介导全麻药对GABA受体D2 A的调节作用。我们正在进行进一步的项目，以阐明局部麻醉剂在重组GABA受体D2 A受体D2 A受体中的作用位点。

项目成果

Fukami S, Uchida I, Takemoshita M, Mashimo T, Yoshiya I.: "The effect of a point mutation of the β2 subunit of GABAィイD2AィエD2 receptor on direct and modulatory actions of general anesthetics."Eur. J. Pharmacol. 368. 269-276 (1999)

Fukami S、Uchida I、Takemoshita M、Mashimo T、Yoshiya I.：“GABAID2AD2 受体 β2 亚基的点突变对全身麻醉药的直接和调节作用的影响。”Eur. J. Pharmacol 368。 276 (1999)

Uchida, I.: "The role of the GABAA receptor α1 subunit N-terminal extracellar domain in propofol potentiation of ohride current"Neuropharmacology. 36. 1611-1621 (1997)

Uchida，I.：“GABAA 受体 α1 亚基 N 末端胞外结构域在丙泊酚增强 ohride 电流中的作用”神经药理学 36. 1611-1621 (1997)

Fukami, S.: "The effects of a point mutation of the β2 subunit of GABAA receptor on direct and medulatory actions of general anestheics"Eur. J. Pharmacol. 368. 269-276 (1999)

Fukami, S.：“GABAA 受体 β2 亚基的点突变对全身麻醉药的直接和调节作用的影响”Eur. J. Pharmacol. 368. 269-276 (1999)

内田 一郎 他: "プロポフォールの薬理作用" ICUとCCU. 22. 225-231 (1998)

Ichiro Uchida 等人：“异丙酚的药理学作用”ICU 和 CCU 22. 225-231 (1998)。

Uchida I, Taenaka N.: "Parmacological actions of propofol"ICU & CCU. 22. 225-231 (1998)

Uchida I, Taenaka N.：“异丙酚的药理学作用”ICU