Changes in benzodiazepine receptors of rat brain after long-term treatment with the Ca(2+)-antagonists nifedipine, verapamil, flunarizine and with the calmodulin antagonist trifluoperazine.
1. The binding of [3H]flunitrazepam to benzodiazepine receptors in the cerebral cortex and hippocampus (membrane fraction P2) was studied after 13-day oral treatment of male Wistar rats with the Ca(2+)-antagonists nifedipine (20 mg/kg), verapamil (50 mg/kg), flunarizine (10 mg/kg) and with the calmodulin (CaM)-antagonist trifluoperazine (TFP) (3 mg/kg). 2. The changes in the binding characteristics of the benzodiazepine receptors in the frontal cortex were studied in vitro after the addition of nifedipine (10(-6) and 10(-5) M) and verapamil (10(-6) and 10(-5) M). 3. A significant decrease of the binding capacity (Bmax) of [3H]flunitrazepam was established after in vivo treatment with the three Ca(2+)-antagonists as well as after TFP, the decrease being much more pronounced in the hippocampus. 4. Changes in the affinity values (Kd) of [3H]flunitrazepam binding were found in neither of the groups. 5. No data for a direct interaction of nifedipine and verapamil with the brain benzodiazepine receptors were obtained in in vitro experiments.
Staneva-Stoytcheva
D
D
Institute of Physiology, Bulgarian Academy of Sciences, Sofia.
Danchev
N
N
Popov
P
P
D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002147:Calmodulin / Q000037:antagonists & inhibitors*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D005444:Flunarizine / Q000494:pharmacology; D005445:Flunitrazepam / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D014268:Trifluoperazine / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002147:Calmodulin; D011963:Receptors, GABA-A; D014268:Trifluoperazine; D005445:Flunitrazepam; D014700:Verapamil; D009543:Nifedipine; D005444:Flunarizine