ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: The interactions of the atypical benzodiazepine 4′-chlorodiazepam (Ro 5-4864) with functionally expressed human GABAA receptor cDNAs were determined. Cotransfection of human α2, β1, and γ2 subunits was capable of reconstituting a 4′-chlorodiazepam recognition site as revealed by a dose-dependent potentiation of t-[35S]butylbicyclophosphorothionate ([35S]TBPS) binding to the GABA-activated chloride channel. This site is found on GABAA receptor complexes containing sites for GABA agonist-like benzodiazepines and neuroactive steroids. The importance of the α subunit was further demonstrated as substitution of either α1 or α3 for the α2 subunit did not reconstitute a 4′-chlorodiazepam recognition site that was capable of modulating [35S]TBPS binding under the same experimental conditions. The 4′-chlorodiazepam modulatory site was shown to be distinct from the benzodiazepine site, but the phenylquinolines PK 8165 and PK 9084 produced effects similar to 4′-chlorodiazepam, consistent with the previous analysis of the 4′-chlorodiazepam site in brain homogenates. Further analysis of the subunit requirements revealed that coexpression of α2 and β1 alone reconstituted a 4′-chlorodiazepam recognition site. It is interesting, however, that the 4′-chlorodiazepam site was found to inhibit [35S]TBPS binding to the GABA-activated chloride channel. Thus, the 4′-chlorodiazepam site may be reconstituted with only the α and β polypeptides.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1046/j.1471-4159.1995.64020684.x
