Type I and type II GABAA-benzodiazepine receptors produced in transfected cells.

Article Details

Citation

Pritchett DB, Luddens H, Seeburg PH

Type I and type II GABAA-benzodiazepine receptors produced in transfected cells.

Science. 1989 Sep 22;245(4924):1389-92.

PubMed ID
2551039 [ View in PubMed
]
Abstract

GABAA (gamma-aminobutyric acid A)-benzodiazepine receptors expressed in mammalian cells and assembled from one of three different alpha subunit variants (alpha 1, alpha 2, or alpha 3) in combination with a beta 1 and a gamma 2 subunit display the pharmacological properties of either type I or type II receptor subtypes. These receptors contain high-affinity binding sites for benzodiazepines. However, CL 218 872, 2-oxoquazepam, and methyl beta-carboline-3-carboxylate (beta-CCM) show a temperature-modulated selectivity for alpha 1 subunit-containing receptors. There were no significant differences in the binding of clonazepam, diazepam, Ro 15-1788, or dimethoxy-4-ethyl-beta-carboline-3-carboxylate (DMCM) to all three recombinant receptors. Receptors containing the alpha 3 subunit show greater GABA potentiation of benzodiazepine binding than receptors containing the alpha 1 or alpha 2 subunit, indicating that there are subtypes within the type II class. Thus, diversity in benzodiazepine pharmacology is generated by heterogeneity of the alpha subunit of the GABAA receptor.

DrugBank Data that Cites this Article

Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
FlumazenilGamma-aminobutyric acid receptor subunit alpha-1Ki (nM)0.49N/AN/ADetails
FlumazenilGamma-aminobutyric acid receptor subunit alpha-1Ki (nM)0.48N/AN/ADetails