Westphalen Robert I, Hemmings Hugh C
Department of Anesthesiology LC-203, Weill Medical College of Cornell University, Box 50, 1300 York Avenue, New York, NY 10021, USA.
J Pharmacol Exp Ther. 2006 Jan;316(1):208-15. doi: 10.1124/jpet.105.090647. Epub 2005 Sep 20.
The effects of three volatile anesthetics (isoflurane, enflurane, and halothane) on basal release of glutamate and GABA from isolated rat cerebrocortical nerve terminals (synaptosomes) were compared using a dual isotope superfusion method. Concentration-dependent effects on basal release differed between anesthetics and transmitters. Over a range of clinical concentrations (0.5-2x minimum alveolar concentration), basal glutamate release was inhibited by all three anesthetics, whereas basal GABA release was enhanced (isoflurane) or unaffected (enflurane and halothane). These effects may represent a balance of stimulatory and inhibitory mechanisms between transmitters and anesthetics. There were no significant differences between anesthetic effects on basal release in the absence or presence of external Ca(2+), whereas intracellular Ca(2+) buffering limited volatile anesthetic inhibition of basal glutamate release. Although these results demonstrate fundamental differences in anesthetic effects on basal release between glutamatergic and GABAergic nerve terminals, all three volatile anesthetics at clinical concentrations consistently reduced the ratio of basal glutamate to GABA release. These actions may contribute to the net depression of glutamatergic excitation and potentiation of GABAergic inhibition characteristic of general anesthesia.
采用双同位素灌流法比较了三种挥发性麻醉剂（异氟烷、恩氟烷和氟烷）对离体大鼠大脑皮质神经末梢（突触体）谷氨酸和γ-氨基丁酸基础释放的影响。麻醉剂和递质对基础释放的浓度依赖性影响有所不同。在一系列临床浓度（0.5 - 2倍最低肺泡浓度）范围内，所有三种麻醉剂均抑制谷氨酸基础释放，而γ-氨基丁酸基础释放则增强（异氟烷）或不受影响（恩氟烷和氟烷）。这些影响可能代表了递质与麻醉剂之间刺激和抑制机制的平衡。在有无细胞外Ca(2+)的情况下，麻醉剂对基础释放的影响无显著差异，而细胞内Ca(2+)缓冲作用限制了挥发性麻醉剂对谷氨酸基础释放的抑制。尽管这些结果表明了麻醉剂对谷氨酸能和γ-氨基丁酸能神经末梢基础释放的影响存在根本差异，但临床浓度下的所有三种挥发性麻醉剂均持续降低了谷氨酸基础释放与γ-氨基丁酸基础释放的比率。这些作用可能有助于全身麻醉所特有的谷氨酸能兴奋的净抑制和γ-氨基丁酸能抑制的增强。
