Structural and functional characterization of the gamma 1 subunit of GABAA/benzodiazepine receptors.
Structural and functional characterization of the gamma 1 subunit of GABAA/benzodiazepine receptors.
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GABAA/苯二氮卓受体 γ1 亚基的结构和功能表征。
DOI：
10.1002/j.1460-2075.1990.tb07525.x
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Peter H. Seeburg
中科院分区：
文献类型：
--
作者：
S. Ymer;Andreas Draguhn;William Wisden;P. Werner;Kari Keinänen;Peter R. Schofield;R. Sprengel;D. B. Pritchett;Peter H. Seeburg
对人、大鼠和牛来源的GABAA受体γ1亚基进行分子克隆，并与γ2亚基进行结构和功能比较。原位杂交证明，两种 γ 亚基变体具有 74% 的序列相似性，并且在中枢神经系统的不同区域中显着合成。当与非洲爪蟾卵母细胞和哺乳动物细胞中的 α 和 β 亚基共表达时，γ 变体介导苯二氮卓类药物对 GABA 诱发电流的增强，并有助于生成这些药物的高亲和力结合位点。然而，这些位点表现出不同的药理学特性，对于由α1、β1和γ1亚基组装的受体来说，其特征是对中性拮抗剂（例如氟马西尼）和负调节剂（例如DMCM）的亲和力明显丧失。这些发现揭示了 γ 亚基变异对 GABAA/苯二氮卓受体药理学的显着影响。
The GABAA receptor gamma 1 subunit of human, rat and bovine origin was molecularly cloned and compared with the gamma 2 subunit in structure and function. Both gamma subunit variants share 74% sequence similarity and are prominently synthesized in often distinct areas of the central nervous system as documented by in situ hybridization. When co‐expressed with alpha and beta subunits in Xenopus oocytes and mammalian cells, the gamma variants mediate the potentiation of GABA evoked currents by benzodiazepines and help generate high‐affinity binding sites for these drugs. However, these sites show disparate pharmacological properties which, for receptors assembled from alpha 1, beta 1 and gamma 1 subunits, are characterized by the conspicuous loss in affinity for neutral antagonists (e.g. flumazenil) and negative modulators (e.g. DMCM). These findings reveal a pronounced effect of gamma subunit variants on GABAA/benzodiazepine receptor pharmacology.