Behavior and cellular evidence for propofol-induced hypnosis involving brain glycine receptors.
Behavior and cellular evidence for propofol-induced hypnosis involving brain glycine receptors.
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DOI：
10.1097/aln.0b013e3181942b5b
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发表时间：
2009-02
期刊：
影响因子：
8.8
通讯作者：
Ye JH
中科院分区：
文献类型：
--
作者：
Nguyen HT;Li KY;daGraca RL;Delphin E;Xiong M;Ye JH
有充分证据表明，包括异丙酚在内的几种全身麻醉剂可增强甘氨酸受体功能。此外，甘氨酸受体存在于整个中枢神经系统中，包括被认为与睡眠有关的大脑区域。然而，甘氨酸受体在麻醉诱导催眠中的作用尚未确定。在大鼠中进行了实验，其中翻正反射的丧失（LORR）被用作催眠状态的标志。在存在和不存在士的宁（一种甘氨酸受体拮抗剂）、GABAzine（一种 γ-氨基丁酸 A 受体拮抗剂）以及氯胺酮（一种谷氨酸受体 N-甲基-D-天冬氨酸亚型拮抗剂）的情况下，检查了异丙酚诱导的 LORR。此外，在从大鼠下丘脑后部分离的神经元中分析了丙泊酚对甘氨酸和γ-氨基丁酸引起的电流的影响。还评估了马钱子碱和伽巴嗪对异丙酚诱导电流的影响。士的宁和伽巴嗪剂量依赖性地降低了异丙酚诱导的出现 LORR 的大鼠的百分比。此外，马钱子碱显着增加了丙泊酚诱导的 LORR 的起效时间并缩短了持续时间。相反，马钱子碱不影响氯胺酮诱导的LORR。此外，异丙酚显着增加了下丘脑神经元甘氨酸和 GABA 引起的电流。相反，马钱子碱和伽巴嗪都极大地减弱了异丙酚诱导的电流。士的宁（甘氨酸受体拮抗剂）剂量依赖性地减少异丙酚诱导的大鼠翻正反射丧失以及异丙酚诱导的大鼠下丘脑神经元电流。这些结果表明神经元甘氨酸受体部分有助于异丙酚诱导的催眠。
It is well documented that several general anesthetics, including propofol, potentiate glycine receptor function. Furthermore, glycine receptors exist throughout the central nervous system, including areas of the brain thought to be involved in sleep. However, the role of glycine receptors in anesthetic-induced hypnosis has not been determined. Experiments were conducted in rats, where the loss of righting reflex (LORR) was used as a marker of the hypnotic state. Propofol-induced LORR was examined in the presence and the absence of strychnine (a glycine receptor antagonist), GABAzine (a γ-aminobutyric acid A receptor antagonist), as well as ketamine (an antagonist of N-methyl-D-aspartic acid subtype of glutamate receptors). Furthermore, the effects of propofol on the currents elicited by glycine and γ-aminobutyric acid were analyzed in neurons isolated from the posterior hypothalamus of rats. The effects of strychnine and GABAzine on propofol-induced currents were also evaluated. Strychnine and GABAzine dose-dependently reduced the percentage of rats exhibiting LORR induced by propofol. Furthermore, strychnine significantly increased the onset time and reduced the duration of LORR induced by propofol. In contrast, strychnine did not affect the LORR induced by ketamine. Additionally, propofol markedly increased the currents elicited by glycine and GABA of hypothalamic neurons. Conversely, strychnine and GABAzine both profoundly attenuated the current induced by propofol. Strychnine, the glycine receptor antagonist dose-dependently reduced propofol-induced loss of righting reflex in rats and propofol-induced current of rat hypothalamic neurons. These results suggest that neuronal glycine receptors partially contribute to propofol-induced hypnosis.