z-logo
Premium
Prevalence between different α subunits performing the benzodiazepine binding sites in native heterologous GABA A receptors containing the α2 subunit
Author(s) -
Carlos del Río Juan,
Araujo Francisco,
Ramos Blanca,
Ruano Diego,
Vitorica Javier
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00551.x
Subject(s) - zolpidem , gabaa receptor , protein subunit , receptor , hippocampal formation , population , binding site , chemistry , heterologous , benzodiazepine , alpha (finance) , heterologous expression , biology , microbiology and biotechnology , biochemistry , pharmacology , endocrinology , medicine , recombinant dna , gene , environmental health , insomnia , construct validity , nursing , patient satisfaction
The presence of two heterologous α subunits and a single benzodiazepine binding site in the GABA A receptor implicates the existence of pharmacologically active and inactive α subunits. This fact raises the question of whether a particular α subtype could predominate performing the benzodiazepine binding site. The hippocampal formation expresses high levels of α subunits with different benzodiazepine binding properties (α1, α2 and α5). Thus, we first demonstrated the existence of α2–α1 (36.3 ± 5.2% of the α2 population) and α2–α5 (20.2 ± 2.1%) heterologous receptors. A similar α2–α1 association was observed in cortex. This association allows the direct comparison of the pharmacological properties of heterologous native GABA A receptors containing a common (α2) and a different (α1 or α5) α subunit. The α2 subunit pharmacologically prevailed over the α1 subunit in both cortex and hippocampus (there was an absence of high‐affinity binding sites for Cl218,872, zolpidem and [ 3 H]zolpidem). This prevalence was directly probed by zolpidem displacement experiments in α2–α1 double immunopurified receptors ( K i  = 295 ± 56 n m and 200 ± 8 n m in hippocampus and cortex, respectively). On the contrary, the α5 subunit pharmacologically prevailed over the α2 subunit (low‐ and high‐affinity binding sites for zolpidem and [ 3 H]L‐655,708, respectively). This prevalence was probed in α2–α5 double immunopurified receptors. Zolpidem displayed a single low‐affinity binding site ( K i  = 1.73 ± 0.54 µ m ). These results demonstrated the existence of a differential dominance between the different α subunits performing the benzodiazepine binding sites in the native GABA A receptors.

This content is not available in your region!

Continue researching here.

Having issues? You can contact us here