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XB-ART-21395
Neuron 1994 Apr 01;124:775-82. doi: 10.1016/0896-6273(94)90330-1.
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A novel allosteric modulatory site on the GABAA receptor beta subunit.

Wafford KA , Bain CJ , Quirk K , McKernan RM , Wingrove PB , Whiting PJ , Kemp JA .


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Cloning of cDNAs that code for GABAA receptor subunits has revealed multiple receptor populations constructed from different subunit combinations. On native rat and cloned human GABAA receptors, the anticonvulsant compound loreclezole strongly potentiated GABA-mediated chloride currents. Using different combinations of human GABAA receptor subunits expressed in Xenopus oocytes and transfected 293 cells, loreclezole was highly selective for receptors containing the beta 2 or beta 3 subunit over those containing the beta 1 subunit. Loreclezole was demonstrated to act at a site distinct from the benzodiazepine, barbiturate, and steroid sites with a unique subunit dependence. These results describe a previously unidentified modulatory site on the GABAA receptor beta subunit that allows pharmacological discrimination of different GABAA receptor subpopulations in the brain and provides a new target for putative anticonvulsant/anxiolytic drugs.

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Species referenced: Xenopus
Genes referenced: gabarap