Flunitrazepam rapidly reduces GABA_A receptor subunit protein expression via a protein kinase C-dependent mechanism

摘要

Acute flunitrazepam (1 μM) exposure 1 h reduced GAB_A receptor α1 (22±4/100, mean ±s.e.mean) and β2/3 (21±4/100)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-((ρ-bromocinnamyl) amino)ethyl]-5-isoquinolinesulfonamide(H-89, 4.8μM), 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.