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Flunitrazepam rapidly reduces GABA A receptor subunit protein expression via a protein kinase C‐dependent mechanism
Author(s) -
Johnston Jonathan D.,
Price Sally A.,
Bristow David R.
Publication year - 1998
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0702012
Subject(s) - flunitrazepam , gabaa receptor , protein kinase a , protein subunit , receptor , kinase , biology , protein kinase c , pharmacology , microbiology and biotechnology , chemistry , biochemistry , gene
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