von Blankenfeld G, Ymer S, Pritchett D B, Sontheimer H, Ewert M, Seeburg P H, Kettenmann H
Department of Neurobiology, University of Heidelberg, F.R.G.
Neurosci Lett. 1990 Jul 31;115(2-3):269-73. doi: 10.1016/0304-3940(90)90467-n.
We compared gamma-aminobutyric acid (GABA)-activated currents and their modulation by benzodiazepines in cultured human cells transfected with complementary desoxyribonucleic acid (cDNA) encoding different GABAA receptor subunits. Flunitrazepam, a benzodiazepine agonist which potentiates GABA responses in both neurons and astrocytes was only effective in receptors containing the gamma 2 subunit (alpha 1 beta 1 gamma 2 and alpha 5 beta 1 gamma 2). The beta-carboline methyl-4-ethyl-6,7-dimethoxy-beta-carboline-3-carboxylate (DMCM) decreased GABA-activated currents in receptors composed of alpha 1 beta 1 gamma 1 and alpha 1 beta 1 gamma 2 subunits but increased GABA-activated currents in receptors containing the alpha 5 subunit (alpha 5 beta 1 gamma 1 and alpha 5 beta 1 gamma 2). These results strongly suggest that flunitrazepam and DMCM do not act on isosteric sites and that differences in the responsiveness of GABAA receptors to these compounds are based on different subunit compositions of GABAA receptors.
