Netopilová M, Drsata J, Haugvicová R, Kubová H, Mares P
Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic.
Neurosci Lett. 1997 Apr 18;226(1):68-70. doi: 10.1016/s0304-3940(97)00241-3.
It has been found that the latency of epileptic seizures caused by glutamate decarboxylase (GAD) inhibitor 3-mercaptopropionate (3-MPA) is markedly longer in immature rats than in the adults. Time course of rat brain GAD inhibition was studied in 12-day-old and adult (90-day-old) animals following 3-MPA (70 mg/kg i.p.). GAD activity was determined by quantification of 14CO2 liberated from [1-(14)C]glutamate by supernatant 20,000 x g of brain homogenate prepared from rats killed at different intervals after 3-MPA administration. In adult rats, the enzyme activity decreased significantly by 14.1% even 1 min after 3-MPA administration and was decreasing gradually till the onset of seizures. In immature rats, GAD activity decrease after 1 min was by 41.4% and further decrease was smaller. Comparison of the time profiles of GAD changes in both groups confirmed our findings that in spite of delayed seizure onset, GAD inhibition in immature rats is more pronounced, probably due to immaturity of the blood-brain barrier.
已发现，谷氨酸脱羧酶（GAD）抑制剂3-巯基丙酸（3-MPA）诱发的癫痫发作潜伏期在幼龄大鼠中明显长于成年大鼠。在12日龄和成年（90日龄）动物中，经腹腔注射3-MPA（70 mg/kg）后，研究大鼠脑GAD抑制的时间进程。通过对3-MPA给药后不同时间点处死的大鼠制备的脑匀浆上清液（20,000×g）中从[1-(14)C]谷氨酸释放的14CO2进行定量，来测定GAD活性。在成年大鼠中，即使在3-MPA给药后1分钟，酶活性也显著下降了14.1%，并且在癫痫发作开始前逐渐下降。在幼龄大鼠中，1分钟后GAD活性下降了41.4%，且进一步下降幅度较小。两组GAD变化时间曲线的比较证实了我们的发现，即尽管癫痫发作延迟，但幼龄大鼠中的GAD抑制更为明显，这可能是由于血脑屏障不成熟所致。
