Comparison of the effect of the GABA uptake blockers, tiagabine and nipecotic acid, on inhibitory synaptic efficacy in hippocampal CA1 neurones
Comparison of the effect of the GABA uptake blockers, tiagabine and nipecotic acid, on inhibitory synaptic efficacy in hippocampal CA1 neurones
复制标题
GABA 摄取阻滞剂噻加宾和哌啶酸对海马 CA1 神经元突触抑制效果的比较
DOI：
10.1016/0304-3940(92)90060-k
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发表时间：
1992
影响因子：
2.5
通讯作者：
J. Lambert
中科院分区：
文献类型：
--
作者：
A. Roepstorff;J. Lambert
用脑片法研究了新型γ-氨基丁酸（GABA）摄取阻滞剂噻加宾对大鼠海马CA 1区锥体细胞GABA能快速抑制性突触后电位（IPSP）和电流（IPSC）的作用。噻加宾（20-50 μM）对IPSC的峰值振幅几乎没有影响，但导致半宽稳健增加（109±15%）。这些结果与使用已确立的摄取阻断剂哌啶甲酸（100 μM至1 mM）获得的结果形成对比，后者使IPSC的振幅降低35±6%，仅导致恢复期适度延长。这些影响，这是不可逆的，可能是解释的事实，即哌啶甲酸是一个基板的GABA摄取载体，可以作为一个错误的发射机。噻加宾不通过GABA载体转运，该物质的结果证明了摄取在确定GABA A受体活化动力学中的作用。建议将噻加宾作为GABA摄取系统的首选阻滞剂。
The action of the novel γ-aminobutyric acid (GABA) uptake blocker, tiagabine, has been studied on isolated GABAergic fast inhibitory postsynaptic potentials (IPSP) and currents (IPSC) in rat hippocampal CA1 pyramidal cells in the slice preparation. Tiagabine (20–50 μM) had little effect on the peak amplitude of the IPSC, but caused a robust increase in the half-width (by 109±15%). These results contrasted with those obtained using the established uptake blocker, nipecotic acid (100 μM to 1 mM), which reduced the amplitude of the IPSC by 35±6% and caused only a modest prolongation of the recovery phase. These effects, which were poorly reversible, are probably explained by the fact that nipecotic acid is a substrate for the GABA-uptake carrier and can act as a false transmitter. Tiagabine is not transported by the GABA carrier and results with this substance demonstrate the role of uptake in determining the kinetics of activation of GABAAreceptors. Tiagabine is proposed as the blocker of choice for the GABA uptake system.