General Anesthetic Binding Sites in Human α4β3δ γ-Aminobutyric Acid Type A Receptors (GABAARs).

ABSTRACT: Extrasynaptic γ-aminobutyric acid type A receptors (GABA_ARs),which contribute generalized inhibitory tone to the mammalian brain, are major targets for general anesthetics. To identify anesthetic binding sites in an extrasynaptic GABA_AR, we photolabeled human α4β3δ GABA_ARs purified in detergent with [³H]azietomidate and a barbiturate, [³H]R-mTFD-MPAB, photoreactive anesthetics that bind with high selectivity to distinct but homologous intersubunit binding sites in the transmembrane domain of synaptic α1β3γ2 GABA_ARs. Based upon ³H incorporation into receptor subunits resolved by SDS-PAGE, there was etomidate-inhibitable labeling by [³H]azietomidate in the α4 and β3 subunits and barbiturate-inhibitable la

SUBMITTER: Chiara DC 

PROVIDER: S-EPMC5159512 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature