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

Acute flunitrazepam (1 μ m ) exposure for 1 h reduced GABA A 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 μ m ), an inhibitor of protein kinase C, but not by N‐[2‐(( p ‐bromocinnamyl)amino)ethyl]‐5‐isoquinolinesulfonamide (H‐89, 4.8 μ m ), an inhibitor of protein kinases A and G. These results suggest the existence of a benzodiazepine‐induced mechanism to rapidly alter GABA A 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