The neurochemical basis for the development of acute tolerance to nitrous oxide

一氧化二氮急性耐受性发展的神经化学基础

• 批准号: 13671601
• 负责人: MURAKAWA Masahiro
• 金额: $ 2.24万
• 依托单位: Fukushima Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671601/
• 关键词: Nitrous oxide; Acute tolerance; Neurotransmitter; Microdialysis; Amino acid; Glutamate; GABA; Glycine; 全身麻酔薬; カテコラミン

To clarify the neurochemical basis for the development of acute tolerance to nitrous oxide, the effects of nitrous oxide on the release of amino acids neurotransmitters in rat cerebral cortex were studied using brain microdialysis. The contents in extracellar amino acids during and after the 4 hours of inhalation of 75% nitrous oxide were measured with high performance liquid chromatography.The release of excitatory neurotransmitter, glutamate, did not significantly change during and after the administration of nitrous oxide. However, the individual glutamate levels markedly decreased or increased within 1 or 2 hours of inhalation of nitrous oxide ; these changes did not restore 2 hours after the cessation of nitrous oxide. The release of inhibitory neurotransmitters, such as gamma amino butyric acid and glycine, showed the tendency of decrease during and after the administration of nitrous oxide. The non transmitter amino acids, such as glutamine, asparagines, taurine, and alanine, revealed the same tendency as the inhibitory neurotransmitters.In this study, nitrous oxide did not apparently affect the neurotransmitter release in the cerebral cortex. However, the effects on the release of glutamate were marked individually. Moreover, these effects did not disappear 2 hours after stopping of nitrous oxide. These findings suggested that nitrous oxide might affect the glutamate neurotransmission ; these effects persisted despite of cessation of this agent. Further studies are needed to elucidate the relationship between the development of acute tolerance and the changes of neurotransmitter release such as glutamate.

为阐明一氧化二氮急性耐受形成的神经化学基础，采用脑微透析技术研究了一氧化二氮对大鼠大脑皮质氨基酸类神经递质释放的影响。用高效液相色谱法测定了吸入75%笑气4 h内及吸入后4 h内细胞外氨基酸的含量，兴奋性神经递质谷氨酸的释放量在吸入笑气期间及吸入后无明显变化。然而，个体谷氨酸水平在吸入一氧化二氮1或2小时内显著降低或升高;这些变化在停止一氧化二氮2小时后没有恢复。抑制性神经递质，如γ-氨基丁酸和甘氨酸的释放，在一氧化二氮给药期间和给药后呈下降趋势。非递质性氨基酸如谷氨酰胺、天冬酰胺、牛磺酸和丙氨酸的释放与抑制性神经递质的释放有相同的趋势，本研究中一氧化二氮对大脑皮层神经递质的释放无明显影响。然而，对谷氨酸释放的影响是单独的。此外，这些影响在停止一氧化二氮后2小时没有消失。这些结果表明，一氧化二氮可能会影响谷氨酸神经传递，这些影响持续存在，尽管停止这种代理。急性耐受的形成与谷氨酸等神经递质释放变化的关系有待进一步研究。

项目成果

Shichino T, Murakawa M, et al.: "Effects of xenon on acetylcholine release in the rat cerebral cortex in vivo"Brit J Anaesth. 88. 866-868 (2002)

Shichino T、Murakawa M 等人：“氙对体内大鼠大脑皮层乙酰胆碱释放的影响”Brit J Anaesth。

Shichino T, Murakawa M, Adachi T, Miyazaki Y, Segawa H, Fukuda K, Mori K: "Effects of xenon on acetylcholine release in the rat cerebral cortex in vivo"Brit J Anaesth. 88. 866-868 (2002)

Shichino T、Murakawa M、Adachi T、Miyazaki Y、Sekawa H、Fukuda K、Mori K：“氙对体内大鼠大脑皮层乙酰胆碱释放的影响”Brit J Anaesth。