Eilers H, Kindler C H, Bickler P E
Department of Anesthesia and Perioperative Care, University of California San Francisco, 94143-0648, USA.
Anesth Analg. 1999 May;88(5):1168-74. doi: 10.1097/00000539-199905000-00037.
Anesthetics cause a reduction in excitatory neurotransmission that may be important in the mechanisms of in vivo anesthetic action. Because glutamate is the major excitatory neurotransmitter in mammalian brain, evaluation of anesthetic effects on induced glutamate release is relevant for studying this potential mechanism of anesthetic action. In the present study, we compared the effects of anesthetics and nonanesthetics (halogenated alkanes that disobey the Meyer-Overton hypothesis) on depolarization-evoked glutamate release. Glutamate released from rat cortical brain slices after chemically induced depolarization (50 mM KCl) was measured continuously using an enzymatic fluorescence assay. The effects of the volatile anesthetics isoflurane and enflurane were compared with the effects of the transitional compound 1,1,2-trichlorotrifluoroethane, the nonanesthetic compound 1,2-dichlorohexafluorocyclobutane, and other polyhalogenated alkanes. Tested concentrations included effective anesthetic concentrations for the anesthetics and transitional compounds, and concentrations predicted to be anesthetic based on lipid solubility for the nonanesthetics. Isoflurane dose-dependently reduced depolarization-evoked glutamate release in cortical brain slices. Isoflurane and enflurane at concentrations equivalent to 1 minimum alveolar anesthetic concentration (MAC) reduced the KCl-evoked release to 20% and 17% of control, respectively. The transitional compound 1,1,2-trichlorotrifluoroethane at 210 microM (approximately 1.2 MAC) reduced glutamate release to 47%, and the nonanesthetic 1,2-dichlorohexafluorocyclobutane increased glutamate release at 70 microM (approximately 3 MAC). These findings support the hypothesis that the modulation of excitatory neurotransmission might be responsible, in part, for in vivo anesthetic action.
The volatile anesthetics isoflurane and enflurane reduce depolarization-evoked glutamate release in rat brain slices. The transitional compound 1,1,2-trichlorotrifluoroethane reduces glutamate release to a much lesser extent, and the nonanesthetic 1,2-dichlorohexafluorocyclobutane does not reduce glutamate release. These findings support the hypothesis that the modulation of excitatory neurotransmission might be responsible, in part, for in vivo anesthetic action.
麻醉剂会导致兴奋性神经传递减少，这在体内麻醉作用机制中可能很重要。由于谷氨酸是哺乳动物大脑中的主要兴奋性神经递质，评估麻醉剂对诱导的谷氨酸释放的影响对于研究这种潜在的麻醉作用机制具有重要意义。在本研究中，我们比较了麻醉剂和非麻醉剂（不符合迈耶-奥弗顿假说的卤代烷烃）对去极化诱发的谷氨酸释放的影响。使用酶荧光测定法连续测量化学诱导去极化（50 mM KCl）后大鼠皮质脑片释放的谷氨酸。将挥发性麻醉剂异氟烷和恩氟烷的作用与过渡化合物1,1,2-三氯三氟乙烷、非麻醉化合物1,2-二氯六氟环丁烷以及其他多卤代烷烃的作用进行了比较。测试浓度包括麻醉剂和过渡化合物的有效麻醉浓度，以及根据非麻醉剂的脂溶性预测为麻醉剂的浓度。异氟烷剂量依赖性地减少皮质脑片中去极化诱发的谷氨酸释放。异氟烷和恩氟烷在相当于1个最低肺泡麻醉浓度（MAC）的浓度下，分别将KCl诱发的释放减少至对照的20%和17%。过渡化合物1,1,2-三氯三氟乙烷在210 microM（约1.2 MAC）时将谷氨酸释放减少至47%，而非麻醉剂1,2-二氯六氟环丁烷在70 microM（约3 MAC）时增加谷氨酸释放。这些发现支持了兴奋性神经传递的调节可能部分负责体内麻醉作用的假说。
挥发性麻醉剂异氟烷和恩氟烷减少大鼠脑片中去极化诱发的谷氨酸释放。过渡化合物1,1,2-三氯三氟乙烷将谷氨酸释放减少的程度要小得多，而非麻醉剂1,2-二氯六氟环丁烷则不会减少谷氨酸释放。这些发现支持了兴奋性神经传递的调节可能部分负责体内麻醉作用的假说。
