High doses of penicillin decreases [3H]flunitrazepam binding sites in rat neuron primary culture.
Penicillin (PC) neurotoxicity (convulsions and encephalopathy) is considered to be due to GABAergic inhibition. The effects of penicillin G(PCG) on [3H]flunitrazepam (FNZ) binding in rat neuron-enriched primary cultures was examined to assess the role of the benzodiazepine (BDZ) receptor in the neurotoxicity. PCG application for 24 h induced a significant decrease in [3H]FNZ binding activity at 10(-3) M, and a decrease in available receptor number (Bmax) at 10(-2) M, without obvious cell damage. Pre-application of the BDZ receptor antagonist, Ro-15-1788, prevented the PC-induced decrease in [3H]FNZ binding activity. Therefore, PC seems to reduce the number of BDZ receptors through a direct effect on this receptor, which is a part of the major inhibitory system in mammalian brain; the GABAergic macromolecular receptor complex. This decrease in BDZ receptors may play a role in PC-induced neurotoxicity, especially encephalopathy.
Shiraishi
H
H
Department of Pediatrics, Shimane Medical University, Izumo, Japan.
Ito
M
M
Go
T
T
Mikawa
H
H
D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005442:Flumazenil / Q000494:pharmacology; D005445:Flunitrazepam / Q000493:pharmacokinetics*; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D010400:Penicillin G / Q000494:pharmacology*; D011247:Pregnancy; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D011963:Receptors, GABA-A; D005442:Flumazenil; D005445:Flunitrazepam; D010400:Penicillin G