Increase of glutamate uptake in astrocytes - A possible mechanism of action of volatile anesthetics
Increase of glutamate uptake in astrocytes - A possible mechanism of action of volatile anesthetics
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DOI：
10.1097/00000542-199706000-00018
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发表时间：
1997-06-01
期刊：
影响因子：
8.8
通讯作者：
Kataoka, K
中科院分区：
文献类型：
--
作者：
Miyazaki, H;Nakamura, Y;Kataoka, K
背景：谷氨酸是脊椎动物中枢神经系统中最普遍存在的兴奋性神经递质。星形胶质细胞通过清除突触间隙释放的谷氨酸，在终止突触能神经传递中发挥重要作用。作者研究了几种麻醉剂对星形胶质细胞摄取谷氨酸活性的影响。方法：将培养的大鼠胚胎脑星形胶质细胞与含[H-3]谷氨酸的溶液孵育，该溶液用0-4%氟烷在37 ℃预平衡，摄取活性以每个细胞蛋白的放射性量来评价。当反应溶液用4%氟烷平衡时，谷氨酸摄取增加至对照的约165%。氟烷的作用呈剂量依赖性，在临床使用浓度范围（1-2%）内观察到谷氨酸摄取显著增加（30-50%）。另一方面，抑制性递质γ-氨基丁酸的摄取几乎不受1-4%氟烷的影响。还在富含神经元的培养物中检查了氟烷对谷氨酸摄取的影响，并且观察到类似的增强，尽管程度小于星形胶质细胞培养物中的增强。神经胶质细胞质膜囊泡和突触体），然而，仅检测到谷氨酸摄取活性的轻微（不显著）增加。其他挥发性麻醉剂，如安氟醚，异氟醚，七氟醚，也增强了谷氨酸的摄取，而静脉麻醉剂氯胺酮和戊巴比妥表现出对谷氨酸uptake.Conclusions没有影响：在挥发性麻醉剂的存在下，星形胶质细胞的谷氨酸摄取的增加可能会减弱兴奋性突触传递在整个中枢神经系统，这一发现可以解释部分挥发性麻醉剂的作用。
Background: Glutamate is the most ubiquitous excitatory neurotransmitter in the vertebrate central nervous system. Astrocytes play an important role in terminating glutamatergic neurotransmission by removing released glutamate from the synaptic cleft. The authors examined the effects of several anesthetics on the glutamate uptake activity of astrocytes,Methods: Cultured astrocytes from hippocampi of rat embryos were incubated with solution containing [H-3]glutamate, which was pre-equilibrated with 0-4% halothane at 37 degrees C, The uptake activity was evaluated as the amount of radioactivity per cell of protein.Results: When the reaction solution was equilibrated with 4% halothane, glutamate uptake increased to about 165% of the control. The effect of halothane was dose-dependent, and a significant augmentation (30-50%) of glutamate uptake was observed at a range in clinical use concentrations (1-2%). On the other hand, the uptake of gamma-aminobutyric acid, an inhibitory transmitter, was hardly affected by 1-4% halothane. The effect of halothane on glutamate uptake was also examined in neuron-rich culture, and similar augmentation was observed, although the extent was less than that in astrocyte culture, Biochemical subcellular fractions (i.e., glial plasmalemmal vesicles and synaptosomes) were also examined, however, only slight (not significant) increase was detected in the glutamate uptake activity. Other volatile anesthetics, such as enflurane, isoflurane, and sevoflurane, also enhanced glutamate uptake, whereas the intravenous anesthetics ketamine and pentobarbital showed no effect on glutamate uptake.Conclusions: The increase of glutamate uptake by astrocytes in the presence of volatile anesthetics potentially attenuates excitatory synaptic transmission in the entire central nervous system, a finding that may explain in part the action of volatile anesthetics.