Pagliusi S R, Gomes C, Leite J R, Trolin G
Naunyn Schmiedebergs Arch Pharmacol. 1983 Apr;322(3):210-5. doi: 10.1007/BF00500767.
The effect of aminooxyacetic acid (AOAA, 90 mg/kg i.v.) on bicuculline, picrotoxin and 3-mercaptopropionic acid (3-MPA) induced convulsions and on GABA concentrations in cerebellum, whole brain and a synaptosomal fraction of whole brain was investigated. At various intervals after AOAA the rats were either injected with one of the convulsive drugs or sacrificed for analysis of the GABA concentration. AOAA caused a rapid initial (0-30 min) and a later slower increase of GABA in cerebellum and whole brain. In the synaptosomal fraction the GABA accumulation was delayed and less pronounced when compared to the whole brain. The bicuculline induced convulsions were markedly potentiated during the first hour but completely blocked from 2-6 h after AOAA. Picrotoxin showed a somewhat different pattern to bicuculline in the interactions with AOAA. The initial strong potentiation was not observed but the later phase of protection was present. In the interactions with 3-MPA, the effect of AOAA was always protective. The time to onset of convulsions was gradually increased during the first 30 min after AOAA. This protective effect remained practically unchanged up to 6 h after AOAA. However, once started, the convulsions were generally of the same duration and intensity. The results can be interpreted as GABA accumulating after AOAA stimulates GABA receptors to a degree more or less proportional to the whole brain GABA concentration and further that GABA synthetized in neurons is liberated, stimulates inhibitory bicuculline sensitive (predominant) and excitatory bicuculline insensitive receptors and is captured to a large extent by non-neuronal cells.
研究了氨氧基乙酸（AOAA，静脉注射90mg/kg）对荷包牡丹碱、印防己毒素和3-巯基丙酸（3-MPA）诱导的惊厥以及对小脑、全脑和全脑突触体部分中γ-氨基丁酸（GABA）浓度的影响。在AOAA给药后的不同时间间隔，给大鼠注射一种惊厥药物或处死以分析GABA浓度。AOAA导致小脑和全脑中GABA迅速出现初始升高（0 - 30分钟），随后升高速度减慢。在突触体部分，与全脑相比，GABA的积累延迟且不明显。荷包牡丹碱诱导的惊厥在最初1小时内明显增强，但在AOAA给药后2 - 6小时完全被阻断。印防己毒素在与AOAA相互作用时表现出与荷包牡丹碱略有不同的模式。未观察到初始的强烈增强作用，但存在后期的保护阶段。在与3-MPA相互作用时，AOAA的作用始终是保护性的。在AOAA给药后的最初30分钟内，惊厥发作的时间逐渐延长。这种保护作用在AOAA给药后6小时内基本保持不变。然而，一旦开始发作，惊厥的持续时间和强度通常相同。这些结果可以解释为，AOAA刺激GABA受体后，GABA积累的程度与全脑GABA浓度或多或少成比例，并且神经元中合成的GABA被释放出来，刺激抑制性的对荷包牡丹碱敏感（主要）和兴奋性的对荷包牡丹碱不敏感的受体，并在很大程度上被非神经元细胞捕获。
