THE PHARMACOLOGY OF THE BENZODIAZEPINE SITE OF THE GABA-A RECEPTOR IS DEPENDENT ON THE TYPE OF GAMMA -SUBUNIT PRESENT

AbstractThe pharmacology of native and recombinant GABA-A receptors containing either γ1, γ2 or γ3 subunits has been investigated. The pharmacology of native receptors has been investigated by immunoprecipitating receptors from solubilised preparations of rat brain with antisera specific for individual γ-subunits and analysing their radioligand binding characteristics. Receptors containing a γ1-subunit do not bind benzodiazepine radioligands with high affinity. Those containing either a γ2 or γ3 subunit bind [3H]flumazenil with high affinity. Some compounds compete for these binding sites with multiple affinities, reflecting the presence of populations of receptors containing several different types of α-subunit. Photoaffinity-labelling of GABA-A receptors from a cell line stably expressing GABA-A receptors of composition α1β3γ2 followed by immunoprecipitation of individual subunits revealed that the α and γ but not the β-subunit could be irreversibly labelled by [3H]flunitrazepam.The properties of recomb...