Heterogeneity in the Allosteric Interaction Between the γ‐Aminobutyric Acid (GABA) Binding Site and Three Different Benzodiazepine Binding Sites of the GABAA/Benzodiazepine Receptor Complex in the Rat Nervous System
Heterogeneity in the Allosteric Interaction Between the γ‐Aminobutyric Acid (GABA) Binding Site and Three Different Benzodiazepine Binding Sites of the GABAA/Benzodiazepine Receptor Complex in the Rat Nervous System
复制标题
大鼠神经系统中 γ-氨基丁酸 (GABA) 结合位点与 GABAA/苯二氮卓受体复合物的三个不同苯二氮卓结合位点之间变构相互作用的异质性
DOI：
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发表时间：
1992
影响因子：
4.7
通讯作者：
J. Vitorica
中科院分区：
文献类型：
--
作者：
D. Ruano;Marisa Vizuete;J. Cano;A. Machado;J. Vitorica
摘要：在本通讯中，我们研究了大鼠不同神经系统区域膜中γ-氨基丁酸A（GABAA）受体与不同的苯二氮卓类（BZD）受体亚型之间的变构偶联。两种类型的BZD受体（I型和II型）已使用CL 218.872进行了经典定义。然而，使用唑吡坦，三种不同的BZD受体已被确定在膜中的结合置换实验。这些BZD受体亚型对唑吡坦表现出高、低和非常低的亲和力。唑吡坦的高亲和力和低亲和力结合位点的分布与小脑、前额皮质和成人大脑皮质中I型和II型亚型的分布相似。另一方面，极低亲和力结合位点在脊髓、海马和新生儿大脑皮层中的比例相对较高，在上级丘中的比例较小。GABAA受体和BZD受体亚型之间的变构偶联是不同的。唑吡坦的高亲和力和低亲和力结合位点似乎具有相似的高度偶联，脊髓除外。另一方面，唑吡坦的极低亲和力结合位点与GABAA受体的偶联程度较低。这些结果似乎表明，GABA在增强[3 H]氟硝西泮结合方面的不同功效可能是由于GABAA/BZD受体复合物中存在不同的BZD受体亚型，此外，还使我们推测在脊髓、海马、和新生儿大脑皮质可能是由于存在相对较高比例的唑吡坦极低亲和力结合位点。
Abstract: In the present communication we have investigated the allosteric coupling between the γ‐aminobutyric acidA (GABAA) receptor and the pharmacologically different benzodiazepine (BZD) receptor subtypes in membranes from various rat nervous system regions. Two types of BZD receptors (type I and type II) have been classically defined using CL 218.872. However, using zolpidem, three different BZD receptors have been identified by binding displacement experiments in membranes. These BZD receptor subtypes displayed high, low, and very low affinity for zolpidem. The distribution of the high‐ and low‐affinity binding sites for zolpidem was similar to that of type I and type II subtypes in cerebellum, prefrontal cortex, and adult cerebral cortex. On the other hand, the very‐low‐affinity binding site was localized in relative high proportion in spinal cord, hippocampus, and newborn cerebral cortex and, to a minor extent, in superior colliculus. The allosteric coupling between the GABAA receptor and the BZD receptor subtypes was different. The high‐ and low‐affinity binding sites for zolpidem seemed to have a similar high degree of coupling, except in spinal cord. On the other hand, the very‐low‐affinity binding site for zolpidem displayed a low degree of coupling with the GABAA receptor. These results seem to indicate that the different efficacy of GABA in enhancing the [3H]flunitrazepam binding could be due to the different BZD receptor subtypes present in the GABAA/BZD receptor complex and, moreover, led us to speculate that the low GABA efficacy found in membranes from spinal cord, hippocampus, and newborn cerebral cortex might be due to the presence in relatively high proportion of the very‐low‐affinity binding site for zolpidem.
γ-氨基丁酸-A 受体蛋白的多个不同亚基表现出不同的配体结合亲和力。
影响因子：
3.6
作者：
Bureau,M;Olsen,RW
通讯作者：
Olsen,RW
苯二氮卓受体与 γ-氨基丁酸 (GABA) 受体亚群偶联：来自定量放射自显影研究的证据。
DOI：
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发表时间：
1981
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Unnerstall,JR;Kuhar,MJ;Niehoff,DL;Palacios,JM
通讯作者：
Palacios,JM