Type I and Type II GABA _A -Benzodiazepine Receptors Produced in Transfected Cells

TLDR

GABA A benzodiazepine receptors expressed in mammalian cells, assembled from α1, α2, or α3 subunits with β1 and γ2, possess high‑affinity benzodiazepine binding sites and exhibit the pharmacological properties of type I or type II subtypes. The study found that temperature‑dependent selectivity for α1‑containing receptors occurs with CL 218 872, 2‑oxoquazepam, and β‑CCM, while clonazepam, diazepam, Ro 15‑1788, and DMCM bind similarly to all three subtypes, and that α3 subunits enhance GABA‑potentiated benzodiazepine binding more than α1 or α2, revealing subtype diversity within type II receptors driven by α subunit heterogeneity.

Abstract

GABA A (γ-aminobutyric acid A)-benzodiazepine receptors expressed in mammalian cells and assembled from one of three different α subunit variants (α 1 , α 2 , or α 3 ) in combination with a β 1 and a γ 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 β-carboline-3-carboxylate (β-CCM) show a temperature-modulated selectivity for α 1 subunit-containing receptors. There were no significant differences in the binding of clonazepam, diazepam, Ro 15-1788, or dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM) to all three recombinant receptors. Receptors containing the α 3 subunit show greater GABA potentiation of benzodiazepine binding than receptors containing the α 1 or α 2 subunit, indicating that there are subtypes within the type II class. Thus, diversity in benzodiazepine pharmacology is generated by heterogeneity of the α subunit of the GABA A receptor.