Contribution of L-type Voltage Sensitive Ca^<2+> Channels to Mechanism of General Anesthesia

L型电压敏感Ca^<2>通道对全身麻醉机制的贡献

• 批准号: 09470323
• 负责人: HIROTA Kazuyoshi
• 金额: $ 8.13万
• 依托单位: Hirosaki University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-09470323/
• 关键词: General anesthetic agents; Noradrenaline; Dopamine; Glutamate; Voltage sensitive Ca^<2+> channel; GABA_A receptor; Rats; Microdialysis; 神経伝達物質; 静脈麻酔薬; アセチルコリン受容体; GABA受容体; 大脳皮質; 線条体; チオペンタール; ペントバルビタール; フェノバルビタール; バルビツール酸; バルビチュレート; カルシ

[In Vitro] We used model of K^+-evoked neurotransmitter (noradrebaline [NA], dopamine and glutamate) release from rat brain slices to study effects of iv anesthetic agents on voltage sensitive Ca^<2+> channels (VSCCs). First, we found that the release is mediated mainly via P/Q-VSCCs. Second, iv anesthetic agents except ketamine significantly inhibit the release in a concentration dependent manner. Thus, these anesthetic agents may inhibit VSCC.However, bicuculline, a GABA_A receptor antagonist, reversed the inhibitory effects of iv anesthetic agents. Therefore, it is likely that activation of GABA_A receptors by these anesthetic agents may reduce VSCC activities.[In Vivo] Using microdialysis method, we studied effects general anesthetic agents on NA release from several brain regions. We found that anesthetics inhibiting NMDA receptor increase NA release, whereas anesthetics activating GABA_A receptor reduce the release. Isoflurane that has both characters decreases the release in the cerebrocortex and increases in the preoptic area of anterior hypothalamus. As sleep-inducing NAergic neurons exist, increase in NA release by NMDA antagonist like anesthetics may contribute to activating sleep-inducing NAergic neurons. In contrast, decrease in NA release by GABA_A agonist like anesthetics may induces inhibition of wakefulness-inducing NAergic neurons.

[In本研究采用K^+诱发的大鼠脑片神经递质去甲肾上腺素（NA）、多巴胺和谷氨酸（Glu）释放模型，研究静脉麻醉药对电压敏感性Ca^2+通道（VSCCs）的影响。首先，我们发现释放主要通过P/Q-VSCC介导。第二，静脉注射除氯胺酮外的麻醉剂均以浓度依赖性方式显著抑制释放。这些麻醉药对VSCC有抑制作用，但GABA_A受体拮抗剂荷包牡丹碱可逆转静脉麻醉药的抑制作用。因此，这些麻醉剂激活GABA_A受体可能会降低VSCC的活动。[In本文采用微透析法研究了全身麻醉药对不同脑区NA释放的影响。麻醉药抑制NMDA受体可增加NA释放，而激活GABA_A受体可减少NA释放。具有这两种特性的异氟醚减少了下丘脑前部视前区的释放，增加了下丘脑前部视前区的释放。由于存在睡眠诱导的NA能神经元，NMDA拮抗剂类麻醉剂增加NA释放可能有助于激活睡眠诱导的NA能神经元。而GABA_A激动剂样麻醉剂减少NA释放则可抑制觉醒诱导的NA能神经元。

项目成果

Kubota T., Anzawa N., Hirota K. et al.: "Effects of ketamine and pentobarbital on norepinephrine release from the median frontal contex in rats"Can J Anaesth. 46. 388-392 (1999)

Kubota T.、Anzawa N.、Hirota K. 等人：“氯胺酮和戊巴比妥对大鼠额叶正中去甲肾上腺素释放的影响”Can J Anaesth。

工藤美穂子 他: "Nociceptin/Orphanin FQのラット大脳皮質切片からのグルタメート放出に及ぼす影響."麻酔と蘇生. 36. 9-10 (2000)

Mihoko Kudo 等人：“伤害感受肽/孤啡宁 FQ 对大鼠大脑皮层切片谷氨酸释放的影响”36. 9-10 (2000)。

Kubota T, et al.: "Effects of sedatives on noradrenaline release from the medial prefrontal cortex in rats. -GABA_A receptor activator vs NMDA receptor inhibitor-."Psychopharmacology. 146. 335-338 (1999)

Kubota T 等人：“镇静剂对大鼠内侧前额皮质去甲肾上腺素释放的影响。-GABA_A 受体激活剂与 NMDA 受体抑制剂-”。精神药理学。

Kubota T, Anzawa N, Hirota K, et al.: "Effects of ketamine and pentobarbital on norepinephrine release from the median frontal cortex in rats."Canadian Journal of Anaesthesia. 46. 388-92 (1999)

Kubota T、Anzawa N、Hirota K 等人：“氯胺酮和戊巴比妥对大鼠中额叶皮质去甲肾上腺素释放的影响。”加拿大麻醉杂志。

Kubota K, Hirota K, Anzawa N, et al.: "Physostigmine antagonizes ketamine-induced noradrenaline release from the medial prefrontal cortex in rats."Brain Research. 840. 175-8 (1999)

Kubota K、Hirota K、Anzawa N 等人：“毒扁豆碱拮抗氯胺酮诱导的大鼠内侧前额皮质去甲肾上腺素的释放。”大脑研究。