FLUNITRAZEPAM RAPIDLY REDUCES GABA(A) RECEPTOR SUBUNIT PROTEIN EXPRESSION VIA A PROTEIN-KINASE C-DEPENDENT MECHANISM

Acute flunitrazepam (1 mu M) exposure for 1 h reduced GABA(A) receptor alpha 1 (22+/-4%, mean +/- s.e. mean) and beta 2/3 (21 +/- 4%) subuni t protein levels in cultured rat cerebellar granule cells. This rapid decrease in subunit proteins was completely prevented by bisindolymale imide 1 (1 mu M), an inhibitor of protein kinase C, but not by omocinn amyl)amino)ethyl]-5-isoquinolinesulfonamide (H-89, 4.8 mu M), an inhib itor of protein kinases A and G. These results suggest the existence o f a benzodiazepine-induced mechanism to rapidly alter GABA(A) receptor protein expression, that appears to be dependent on protein kinase C activity.