Characterization of benzodiazepine receptors in the cerebellum.
Characterization of benzodiazepine receptors in the cerebellum.
复制标题
小脑中苯二氮卓受体的表征。
DOI：
10.1016/s0278-5846(00)00114-7
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发表时间：
2000
影响因子：
5.6
通讯作者：
Loew,GH
中科院分区：
文献类型：
--
作者：
Lameh,J;Wang,P;Meredith,D;Shafer,SL;Loew,GH
1.本文报告的工作目标是进一步表征小脑中苯二氮卓类/GABA（A）（BDZR）受体的异质性，并测量结构不同的苯二氮卓类药物在每个位点的亲和力和选择性。2.这些研究包括五个化学家族。这些是1，4-苯并二氮杂卓类（氟硝西泮）、咪唑并苯并二氮杂卓类（RO 15 -1788和RO 15 -4513和RO 16 -6028）、β-咔啉类（Abecarnil）和吡唑并喹啉类（CGS 8216、CGS 9895和CGS 9896）。3.饱和和竞争结合试验与我们实验室开发的强大的数据分析软件相结合。该软件的功能之一是使用非选择性标记配体识别冷配体的多个结合位点，所述非选择性标记配体以相等但高的亲和力结合所有结合位点4。使用[3 H]-RO 15 -1788或[3 H]-RO 15 -4513的饱和结合试验仅显示一个表观结合位点，对RO 15 -4513的亲和力高于RO 15 -1788。然而，使用[3 H]-RO 15 -4513进行小脑中的竞争结合研究，以及我们的数据分析软件，导致识别出所研究的不同苯二氮卓类药物的两个具有相同密度的不同结合位点。5.在大鼠小脑中，鉴定的位点之一对应于表现α 1亚单位药理学的GABA（A）受体，另一个对应于表现α 6亚单位药理学的GABA（A）受体。一般而言，所研究的BDZR配体的不同家族对含有α 6的受体具有低得多的亲和力。
1. The goals of the work reported here were to further characterize benzodiazepine/GABA (A)(BDZR) receptor heterogeneity in the cerebellum and to measure the affinities and selectivities of structurally diverse benzodiazepines at each site identified. 2. Five chemical families were included in these studies. These were 1, 4-benzodiazepines (flunitrazepam), imidazobenzodiazepines (RO15-1788 and RO15-4513 and RO16-6028), beta-carbolines (Abecarnil) and pyrazoloquinolines (CGS 8216, CGS 9895 and CGS 9896). 3. Saturation and competition binding assays were combined with powerful data analysis software developed in our laboratory. Among the capabilities of this software is the identification of multiple binding sites for a cold ligand using a non-selective labeled ligand that binds with equal, but high, affinity to all the binding sites 4. Saturation binding assays using either [3H]-RO15-1788 or [3H]-RO15-4513 revealed only one apparent binding site, with a higher affinity for RO15-4513 than for RO15-1788. However, using [3H]-RO15-4513 for the competition binding studies in the cerebellum, together with our data analysis software, led to the identification of two distinct binding sites with equal densities for the diverse benzodiazepines studied. 5. In rat cerebellum one of the sites identified corresponds to GABA (A) receptors exhibiting alpha1 subunit pharmacology and the other to GABA (A) receptors exhibiting alpha6 subunit pharmacology. In general, the diverse families of BDZR ligands studied had much lower affinities for the alpha6 containing receptors.