Bertilsson L, Mao C C, Costa E
J Pharmacol Exp Ther. 1977 Feb;200(2):277-84.
13C-labeled glucose (50 mumol/kg/min) was infused into the rat tail vein for 10 minutes. The animals were killed by a microwave beam focused to the skull at various times after the infusion. In brain nuclei the concentrations of glutamate and gamma-aminobutyric acid (GABA) and their enrichment in 13C were measured by mass fragmentography. The results showed that in the five brain areas studied, substantia nigra contained the highest GABA concentration, followed by globus pallidus, N. accumbens, deep cerebellar nuclei, N. caudatus and cerebellar cortex. The concentrations of glutamate and GABA were comparable in some nuclei (substantia nigra and globus pallidus), but not in others. The glutamate content was 3 to 6 times greater than GABA content in cerebellum (cortex and nuclei) N. accumbens and N. caudatus. The turnover rates of GABA in substantia nigra, globus pallidus, N. caudatus and N. accumbens were calculated by applying principles of steady-state kinetics to the changes with time in the 13C enrichment of glutamic acid and GABA. In substantia nigra, N. accumbens and N. caudatus, the percentage of 13C incorporation into glutamic acid and GABA reached its maximum 10 to 15 minutes after the infusion. In N. caudatus and N. accumbens, the percentage of 13C incorporation into GABA was higher than that in substantia nigra and globus pallidus. The turnover rates of GABA were very similar in N. caudatus, N. accumbens, substantia nigra and globus pallidus (385-562 nmol/mg of protein per hr), but the turnover times were much faster in N. caudatus and N. accumbens. It must be kept in mind that in N. caudatus and N. accumbens the glutamate pool was several-fold greater than that of GABA. Since the data obtained indicate that the compartmentation is more complicated than in the model assumed for turnover estimations, this method should be used only for comparative purposes in drug studies. The validity of this method to obtain absolute measurements of GABA turnover remains to be documented.
将13C标记的葡萄糖（50微摩尔/千克/分钟）注入大鼠尾静脉10分钟。在注入后不同时间，用聚焦于颅骨的微波束处死动物。通过质量碎片分析法测定脑核中谷氨酸和γ-氨基丁酸（GABA）的浓度及其13C富集情况。结果表明，在所研究的五个脑区中，黑质的GABA浓度最高，其次是苍白球、伏隔核、小脑深部核团、尾状核和小脑皮质。在某些核团（黑质和苍白球）中，谷氨酸和GABA的浓度相当，但在其他核团中并非如此。在小脑（皮质和核团）、伏隔核和尾状核中，谷氨酸含量比GABA含量高3至6倍。通过将稳态动力学原理应用于谷氨酸和GABA的13C富集随时间的变化，计算黑质、苍白球、尾状核和伏隔核中GABA的周转率。在黑质、伏隔核和尾状核中，注入后10至15分钟，13C掺入谷氨酸和GABA的百分比达到最大值。在尾状核和伏隔核中，13C掺入GABA的百分比高于黑质和苍白球。尾状核、伏隔核、黑质和苍白球中GABA的周转率非常相似（385 - 562纳摩尔/毫克蛋白质/小时），但尾状核和伏隔核中的周转时间要快得多。必须记住，在尾状核和伏隔核中，谷氨酸池比GABA池大几倍。由于所获得的数据表明，其区室化比用于周转率估计的假设模型更为复杂，因此该方法仅应用于药物研究中的比较目的。该方法用于获得GABA周转率绝对测量值的有效性仍有待证实。
