Ymer S, Draguhn A, Wisden W, Werner P, Keinänen K, Schofield P R, Sprengel R, Pritchett D B, Seeburg P H
Laboratory of Molecular Neuroendocrinology, University of Heidelberg, FRG.
EMBO J. 1990 Oct;9(10):3261-7. doi: 10.1002/j.1460-2075.1990.tb07525.x.
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.
对人、大鼠和牛源的GABAA受体γ1亚基进行了分子克隆，并在结构和功能上与γ2亚基进行了比较。两种γ亚基变体具有74%的序列相似性，原位杂交证明它们在中枢神经系统的不同区域大量合成。当与α和β亚基在非洲爪蟾卵母细胞和哺乳动物细胞中共表达时，γ变体介导苯二氮䓬类药物对GABA诱发电流的增强作用，并有助于产生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亚基组装而成的受体，其特征是对中性拮抗剂（如氟马西尼）和负性调节剂（如DMCM）的亲和力显著丧失。这些发现揭示了γ亚基变体对GABAA/苯二氮䓬类受体药理学有显著影响。
