Flunitrazepam rapidly reduces GABAA receptor subunit protein expression via a protein kinase C‐dependent mechanism

Abstract
Acute flunitrazepam (1 μm) exposure for 1 h reduced GABAA receptor α1 (22±4%, mean±s.e.mean) and β2/3 (21±4%) subunit protein levels in cultured rat cerebellar granule cells. This rapid decrease in subunit proteins was completely prevented by bisindolymaleimide 1 (1 μm), an inhibitor of protein kinase C, but not by N‐[2‐((p‐bromocinnamyl)amino)ethyl]‐5‐isoquinolinesulfonamide (H‐89, 4.8 μm), an inhibitor of protein kinases A and G. These results suggest the existence of a benzodiazepine‐induced mechanism to rapidly alter GABAA receptor protein expression, that appears to be dependent on protein kinase C activity.British Journal of Pharmacology (1998) 124, 1338–1340; doi:10.1038/sj.bjp.0702012

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