Abstract
γ-Aminobutyric acid type A (GABA(A)) receptor subtypes containing the α6-subunit are generally thought to be insensitive to the action of benzodiazepine agonists. We describe the specific binding of the benzodiazepine agonist flunitrazepam to α6β2γ2-containing GABA(A) receptors, which has not been observed before and differs from previous reports. With the whole-cell voltage-clamp technique, we observed a functional discrimination between α1β2γ2 and α6β2γ2-receptors. Different benzodiazepines had different effects on GABA-evoked chloride currents. The agonist flunitrazepam had an inverse agonistic effect, whereas the antagonist flumazenil increased GABA-induced chloride currents. The action of flunitrazepam on the channel activity of α6β2γ2-receptors was opposite to its action on α1β2γ2-receptors. We conclude that flunitrazepam can act as either an agonist or an inverse agonist, depending on the GABA(A) receptor configuration.
Original language | English (US) |
---|---|
Pages (from-to) | 11723-11727 |
Number of pages | 5 |
Journal | Journal of Biological Chemistry |
Volume | 272 |
Issue number | 18 |
DOIs | |
State | Published - May 2 1997 |
ASJC Scopus subject areas
- Biochemistry