Expression and properties of recombinant alpha 1 beta 2 gamma 2 and alpha 5 beta 2 gamma 2 forms of the rat GABAA receptor

Eur J Pharmacol. 1993 Aug 15;246(3):283-7. doi: 10.1016/0922-4106(93)90043-9.


The interaction of omega (benzodiazepine) modulatory drugs with transiently expressed alpha 1 beta 2 gamma 2 and alpha 5 beta 2 gamma 2 forms of the rat GABAA receptor was investigated using [3H]flumazenil as a probe in in vitro radioligand binding assays. The imidazopyridines alpidem and zolpidem exhibited pronounced selectivity for the alpha 1- compared to the alpha 5-containing construct, whereas omega (benzodiazepine) site modulatory compounds from other chemical series including diazepam, tetrazepam, zopiclone, triazolam, bretazenil and midazolam behaved as relatively non-selective drugs. In the presence of 10 microM gamma-aminobutyric acid (GABA) the potencies of diazepam, flunitrazepam and midazolam to inhibit [3H]flumazenil binding to the alpha 1-construct were increased 3 to 5 fold, whereas with 6,7-dimethoxy-4-ethyl-beta-carboline-3-carboxylate methyl ester a 2.5-fold reduction in potency was observed. Similar modulatory effects of GABA were obtained with these drugs, using the alpha 5-construct. We suggest that these GABA shift determinations of [3H]flumazenil binding can be used as a rapid test to evaluate the intrinsic activities of omega modulatory compounds.

MeSH terms

  • Animals
  • Binding, Competitive / physiology
  • Flumazenil / metabolism*
  • Humans
  • Muscimol / metabolism
  • Radioligand Assay
  • Rats
  • Receptors, GABA-A / metabolism*
  • Recombinant Proteins / metabolism


  • Receptors, GABA-A
  • Recombinant Proteins
  • Muscimol
  • Flumazenil