Temporal and regional regulation of alpha1, beta2 and beta3, but not alpha2, alpha4, alpha5, alpha6, beta1 or gamma2 GABA(A) receptor subunit messenger RNAs following one-week oral flurazepam administration.
Temporal and regional regulation of alpha1, beta2 and beta3, but not alpha2, alpha4, alpha5, alpha6, beta1 or gamma2 GABA(A) receptor subunit messenger RNAs following one-week oral flurazepam administration.
复制标题
口服氟西泮一周后，α1、β2 和 β3 的时间和区域调节，但 α2、α4、α5、α6、β1 或 γ2 GABA(A) 受体亚基信使 RNA 没有调节。
DOI：
10.1016/s0306-4522(98)00516-8
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发表时间：
1999
期刊：
影响因子：
3.3
通讯作者：
Ferencak3rd,WF
中科院分区：
文献类型：
--
作者：
Tietz,EI;Huang,X;Chen,S;Ferencak3rd,WF
研究了苯二氮卓类药物长期给药对大鼠海马和皮质等脑区GABA A受体亚单位（α1-6，β1-3，γ2）信使RNA的影响。大鼠口服给予泮一周，这是一种导致体内苯二氮卓类抗惊厥耐受性的方案，在体外海马中，在没有戒断行为体征的情况下。与[35 S]寡探针原位杂交的脑切片的放射自显影，在药物处理后立即（第0天）或两天（当大鼠耐受时）或处理后7天（当耐受逆转时）进行检查，并与成对处理的溶剂处理对照切片进行比较。海马CA 1区锥体细胞和齿状颗粒细胞α1亚基mRNA水平在第0天显著降低，这种作用仅在CA 1区神经元中持续存在。锥体细胞边缘的中间神经元亚类上的“α1特异性”银颗粒密度降低表明中间神经元GABAA受体的伴随调节。给药后即刻和2天，海马细胞组（CA 1、CA 2、CA 3和齿状回）中β3亚基信使RNA水平的降低更为普遍，并且在额叶和顶枕皮质中也检测到了这种降低。停药后2天海马CA 1、CA 3和齿状回细胞β2亚基mRNA水平的变化提示β2 mRNA水平上调。停药7 d后，海马CA 1、CA 3和齿状回细胞α5、β3和γ 2亚基mRNA水平有升高趋势，其中以额叶皮质β3和γ2亚基mRNA水平升高最为显著。在任何其他GABA A受体亚单位信使RNA中没有发现泮处理诱导的变化。9个GABA A受体亚基中的3个（α1、β2和β3）的信使RNA水平在结束一周的泮治疗后作为时间的函数被离散地调节，这与抗惊厥药物耐受性的存在有关，但与依赖性无关。研究结果表明，涉及这些特定亚基的GABA A受体亚型亚基组成的局部开关可能代表了先前在海马CA 1 GABA能突触记录的GABA A受体介导的功能变化的最低要求，与苯二氮卓类抗惊厥耐受相关。
The effect of prolonged benzodiazepine administration on GABAAreceptor subunit (α1–6, β1–3, γ2) messenger RNAs was investigated in the rat hippocampus and cortex, among other brain areas. Rats were orally administered flurazepam for one week, a protocol which results in benzodiazepine anticonvulsant tolerance in vivo, and in the hippocampus in vitro, in the absence of behavioral signs of withdrawal. Autoradiographs of brain sections, hybridized with [35S]oligoprobes in situ, were examined immediately (day 0) or two days after drug treatment, when rats were tolerant, or seven days after treatment, when tolerance had reversed, and were compared to sections from pair-handled, vehicle-treated controls. α1 subunit messenger RNA level was significantly decreased in CA1 pyramidal cells and dentate granule cells at day 0, an effect which persisted only in CA1 neurons. Decreased “α1-specific” silver grain density over a subclass of interneurons at the pyramidal cell border suggested concomitant regulation of interneuron GABAAreceptors. A reduction in β3 subunit messenger RNA levels was more widespread among hippocampal cell groups (CA1, CA2, CA3 and dentate gyrus), immediately and two days after treatment, and was also detected in the frontal and parieto-occipital cortices. Changes in β2 subunit messenger RNA levels in CA1, CA3 and dentate gyrus cells two days after ending flurazepam treatment suggested a concomitant up-regulation of β2 messenger RNA. There was a trend toward an increased level of α5, β3 and γ2 subunit messenger RNAs in CA1, CA3 and dentate gyrus cells, which was significant for the β3 and γ2 subunit messenger RNAs in the frontal cortex seven days after ending flurazepam treatment. There were no flurazepam treatment-induced changes in any other GABAAreceptor subunit messenger RNAs. The messenger RNA levels of three (α1, β2 and β3) of nine GABAAreceptor subunits were discretely regulated as a function of time after ending one-week flurazepam treatment related to the presence of anticonvulsant tolerance, but not dependence. The findings suggested that a localized switch in the subunit composition of GABAAreceptor subtypes involving these specific subunits may represent a minimal requirement for the changes in GABAAreceptor-mediated function recorded previously at hippocampal CA1 GABAergic synapses, associated with benzodiazepine anticonvulsant tolerance.