Regional distribution and kinetics of three sites on the GABAA receptor: lack of effect of portacaval shunting.
Regional distribution and kinetics of three sites on the GABAA receptor: lack of effect of portacaval shunting.
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GABAA 受体上三个位点的区域分布和动力学：缺乏门静脉分流的作用。
DOI：
10.1038/jcbfm.1992.46
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发表时间：
1992
期刊：
影响因子：
--
通讯作者：
Rokosz,NC
中科院分区：
文献类型：
--
作者：
Mans,AM;Kukulka,KM;McAvoy,KJ;Rokosz,NC
GABA受体结合位点的区域分布及其动力学参数的定量放射自显影测定在正常大鼠和大鼠的门腔静脉分流，门脉系统性脑病，其中GABA神经传递可能会改变的模型的大脑。使用的配体为[3 H]氟硝西泮（苯二氮卓类位点激动剂）、[3 H]-Ro 15-1788（苯二氮卓类位点拮抗剂）、[3 H]蝇蕈醇（GABA位点激动剂）和[35 S]叔丁基双环硫代磷酸酯（35 S-TBPS，一种与氯离子通道附近位点结合的惊厥剂）。部分脑组织通过计算机图像分析和三维重建进行分析。苯二氮卓类药物结合的区域分布非常相似，但[3 H]蝇蕈醇和[35 S]TBPS在许多区域获得的模式不同，表明GABAA受体的几种亚型分布不均匀。在脑区测定[3 H]氟硝西泮、[3 H] Ro 15 -1788和[3 H]蝇蕈醇的动力学参数。对于每个配体，kd显示出显着的异质性之间的大脑区域（至少三倍），从早期的研究得出的结论相反。在门腔静脉分流大鼠中，所有四种配体的结合与对照大鼠相比基本上没有变化，这表明，如果在门静脉系统分流期间GABA神经传递异常，则不能通过改变与GABAA受体主要位点的结合来反映。
The regional distribution of binding sites on the GABAAreceptor and their kinetic parameters were measured by quantitative autoradiography in brains from normal rats and rats with a portacaval shunt, a model of portal systemic encephalopathy in which GABA neurotransmission may be altered. The ligands used were [3H]flunitrazepam (a benzodiazepine-site agonist), [3H]-Ro 15-1788 (a benzodiazepine-site antagonist), [3H]muscimol (a GABA-site agonist), and [35S]t-butylbicyclo-phosphorothionate (35S-TBPS, a convulsant that binds to a site near the chloride channel). Some brains were analyzed by computerized image analysis and three-dimensional reconstruction. The regional distribution of binding of the benzodiazepines was very similar, but the patterns obtained with [3H]muscimol and [35S]TBPS were different in many areas, suggesting a heterogeneous distribution of several subtypes of the GABAAreceptor. The kinetic parameters were determined in brain regions for [3H]flunitrazepam, [3H]Ro15-1788, and [3H]muscimol. For each ligand, theKdshowed a significant heterogeneity among brain regions (at least threefold), contrary to conclusions drawn from earlier studies. In portacaval shunted rats, binding of all four ligands was essentially unchanged from that in control rats, indicating that, if there was an abnormality in GABA neurotransmission during portal systemic shunting, it was not reflected by altered binding to the main sites on the GABAAreceptor.