GAMMA-AMINOBUTYRIC ACIDA RECEPTOR ALPHA-5-SUBUNIT CREATES NOVEL TYPE-II BENZODIAZEPINE RECEPTOR PHARMACOLOGY

Abstract: A cDNA encoding a protein with 70% amino acid identity to the previously characterized γ‐aminobutyric acidA (GABAA receptor α‐subunits was isolated from a rat brain cDNA library by homology screening. As observed for α1‐, α2‐, and α3‐subunits, coexpression of this new α‐subunit (α5) with a β‐ and γ2‐subunit in cultured cells produces receptors displaying high‐affinity binding sites for both muscimol, a GABA agonist, and benzodiazepines. Characteristic of GABAA/benzodiazepine type II sites, receptors containing α2‐, α3‐ or α5‐subunits have low affinities for several type I‐selective compounds. However, α5‐subunit‐containing receptors have lower affinities for zolpidem (30‐fold) and Cl 218 872 (three‐fold) than measured previously using recombinantly expressed type II receptors containing either α2‐ or α3‐subunits. Based on these findings, a reclassification of the GABAA/benzodiazepine receptors is warranted. Copyright © 1990, Wiley Blackwell. All rights reserved