药物引起的11个大鼠脑区神经末梢γ-氨基丁酸含量的变化。与药理作用的相关性。

Drug-induced changes in GABA content of nerve endings in 11 rat brain regions. Correlation to pharmacological effects.

作者信息

Löscher W, Vetter M

出版信息

Neurosci Lett. 1984 Jun 29;47(3):325-31. doi: 10.1016/0304-3940(84)90534-2.

Abstract

For determination of in vivo drug effects on nerve terminal GABA, a procedure was used which allowed the simultaneous measurement of GABA in nerve endings (synaptosomes) from 11 regions of one rat brain. Synaptosomal fractions were prepared by conventional subcellular fractionation procedures and characterized by electron microscopy. Postmortem increases of GABA during removal and dissection of brain tissue, homogenization and fractionation procedures could be sufficiently minimized by rapid processing of the tissue at low temperatures and inclusion of 3-mercaptopropionic acid (1 mM) in the homogenizing medium. In vivo experiments with the GABA-elevating drugs aminooxyacetic acid (30 mg/kg i.p.) and valproic acid (200 mg/kg i.p.) showed that both drugs caused differential effects on synaptosomal GABA levels in different brain regions. A comparison of these biochemical effects with anticonvulsant effects of both drugs in different seizure models supports the concept that GABA synapses in midbrain areas are critically involved in the control of seizure propagation.

摘要

为了测定体内药物对神经末梢γ-氨基丁酸（GABA）的影响，采用了一种方法，该方法能够同时测量来自一只大鼠大脑11个区域的神经末梢（突触体）中的GABA。通过传统的亚细胞分级分离程序制备突触体组分，并通过电子显微镜进行表征。在去除和解剖脑组织、匀浆和分级分离过程中，通过在低温下快速处理组织并在匀浆介质中加入3-巯基丙酸（1 mM），可以充分减少死后GABA的增加。使用提高GABA水平的药物氨氧基乙酸（腹腔注射30 mg/kg）和丙戊酸（腹腔注射200 mg/kg）进行的体内实验表明，这两种药物对不同脑区的突触体GABA水平产生了不同的影响。将这些生化效应与这两种药物在不同癫痫模型中的抗惊厥作用进行比较，支持了中脑区域的GABA突触在癫痫发作传播控制中起关键作用的概念。