Gaba-benzodiazepine receptor complex in brain oxidative metabolism regulation.
This study investigated the impact of modulating the gamma-aminobutyric acid(A) (GABA)(A)-benzodiazepine receptor complex activity on the rat frontal cortex slices oxygen consumption (QO(2)), polarographically determined using the biological oxygen monitor. Throughout the study, diazepam, flumazenil and picrotoxin were administered i.p. 30 min before sacrificing animals and obtaining slice preparations, while GABA was added directly into the medium in the reaction chamber. GABA decreased QO(2) in concentrations of 5 x 10(-4), 10(-2) and 5 x 10(-2)mol l(-1), while 10(-5) and 10(-6)mol l(-1) GABA had no effect, as well as diazepam, flumazenil and picrotoxin. All diazepam doses (1, 2.5 and 5 mg kg(-1)) increased action of 5 x 10(-4)mol l(-1) GABA, whereas 2.5 mg kg(-1) dose amplified the effect of 10(-6)mol l(-1) GABA. Flumazenil and picrotoxin (5 mg kg(-1) both) blocked diazepam's effects. Flumazenil augmented 10(-6)mol l(-1) GABA effects, while picrotoxin and flumazenil abolished the effects of 5 x 10(-4)mol l(-1) GABA. To our knowledge, this is the first study to examine the influence of modulation of GABA(A)-benzodiazepine receptor function on cerebral metabolism of oxygen in in vitro settings. The results are in accordance with those obtained in numerous in vivo studies, pointing to the moderate level of influence of GABA(A)-benzodiazepine receptor complex on QO(2) regulation.
Obradović
Dragan I
DI
Department of Pharmacology, Medical Faculty, University of Belgrade, Vojvode Stepe 450, 11221 Belgrade, Yugoslavia.
Bokonjić
Dubravko R
DR
Savić
Miroslav M
MM
Andjelković
Draginja S
DS
Ugresić
Nenad D
ND
Stojilković
Milos P
MP
D000818:Animals; D003975:Diazepam / Q000494:pharmacology; D005442:Flumazenil / Q000494:pharmacology; D005625:Frontal Lobe / Q000378:metabolism*; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D007274:Injections, Intraperitoneal; D008297:Male; D010101:Oxygen Consumption / Q000187:drug effects*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology*
D003975:Diazepam; D005442:Flumazenil; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid