Regulation of GABA(A) receptor alpha1 protein is a sensitive indicator of benzodiazepine agonist efficacy.
The effect of benzodiazepine agonists of varying efficacy on gamma-aminobutyric acidA receptor alpha1 subunit protein expression was determined in primary cultured cerebellar granule cells. After 48 h exposure to 1 microM drug concentrations, flunitrazepam, diazepam, and the partial agonists Ro 19-8022 and bretazenil, but not the partial agonists Ro 42-8773, Ro 41-7812 or imidazenil, decreased alpha1 subunit protein expression. The grading of effect of the benzodiazepine partial agonists on alpha1 subunit protein expression is consistent with their agonist efficacies. This model, therefore, appears to act as a sensitive indicator of benzodiazepine agonist efficacy with the ability to differentiate between partial agonists.
Johnston
J D
JD
Division of Neuroscience, School of Biological Sciences, University of Manchester, UK.
Bristow
D R
DR
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D001569:Benzodiazepines / Q000819:agonists*; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000378:metabolism; D003975:Diazepam / Q000494:pharmacology; D005445:Flunitrazepam / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D011807:Quinolizines / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000096:biosynthesis* / Q000235:genetics
D014151:Anti-Anxiety Agents; D018757:GABA Modulators; D011759:Pyrrolidines; D011807:Quinolizines; D011963:Receptors, GABA-A; C076809:Ro 19-8022; D001569:Benzodiazepines; D005445:Flunitrazepam; D003975:Diazepam