Inhibition of glutamate decarboxylase activity by 3-mercaptopropionic acid has different time course in the immature and adult rat brains

Inhibition of glutamate decarboxylase activity by 3-mercaptopropionic acid has different time course in the immature and adult rat brains
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DOI:
10.1016/s0304-3940(97)00241-3
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发表时间:
1997-04-18
影响因子:
2.5
通讯作者:
Mares, P
Mares, P
中科院分区:
医学4区
文献类型:
--
作者:
Netopilova, M;Drsata, J;Mares, P

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谷氨酸脱羧酶(GAD)抑制剂3-巯基丙酸酯(3-MPA)诱发幼鼠癫痫发作的潜伏期明显长于成年鼠。在12日龄和成年(90日龄)动物中研究了3-MPA(70 mg/kg i. p.)给药后大鼠脑GAD抑制的时程。GAD活性通过定量(CO2)-C-14从[1-C-14]谷氨酸盐中释放,通过上清液20 000 x g脑匀浆(从3-MPA给药后不同时间间隔处死的大鼠制备)测定。在成年大鼠中,3-MPA给药后1 min,酶活性显著下降14.1%,并逐渐下降,直到癫痫发作。幼鼠GAD活性在1 min后下降41.4%,进一步下降幅度较小。两组中GAD变化的时间曲线的比较证实了我们的发现,尽管延迟癫痫发作,GAD抑制在未成熟大鼠更明显,可能是由于血脑屏障的不成熟。(C)1997 Elsevier Science爱尔兰有限公司
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 (CO2)-C-14 liberated from [1-C-14]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. (C) 1997 Elsevier Science Ireland Ltd.