Effects of 1-amino-5-bromouracil on the benzodiazepine-GABAA receptor complex.
We investigated the effects of 1-amino-5-bromouracil on the benzodiazepine-gamma-aminobutyric acid (GABA)A receptor complex to elucidate its central action. 1-Amino-5-bromouracil neither displaced nor enhanced [3H]muscimol, [35S]t-butylbicyclophosphorothionate (TBPS), or [3H]dehydroepiandrosterone sulfate binding to the rat brain synaptosomal membranes. The anesthesia induced by 1-amino-5-bromouracil was potentiated by diazepam, pentobarbital, and muscimol, and was antagonized by picrotoxin but not by bicuculline. 1-Amino-5-bromouracil protected mice from picrotoxin-induced seizure and slightly ameliorated TBPS-induced seizure, but did not antagonize bicuculline-induced seizure. Diazepam antagonized both the bicuculline- and the picrotoxin-induced seizure, and pentobarbital antagonized the picrotoxin- and the TBPS-induced seizure. Our in vivo studies suggest that part of the central action of 1-amino-5-bromouracil is concerned with the benzodiazepine-GABAA receptor complex including the chloride channel.
Miyazaki
S
S
Biology Laboratory, Yamasa Corporation, Chiba, Japan.
Imaizumi
M
M
Machida
H
H
D000758:Anesthesia; D000818:Animals; D014151:Anti-Anxiety Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000927:Anticonvulsants / Q000494:pharmacology; D001643:Bridged Bicyclo Compounds / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001976:Bromouracil / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D003292:Convulsants / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology; D003687:Dehydroepiandrosterone / Q000378:metabolism; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009118:Muscimol / Q000378:metabolism / Q000494:pharmacology; D010852:Picrotoxin / Q000037:antagonists & inhibitors / Q000633:toxicity; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000187:drug effects*; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism
D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001976:Bromouracil; D003292:Convulsants; D003687:Dehydroepiandrosterone; D009118:Muscimol; D010852:Picrotoxin; D011963:Receptors, GABA-A; C037476:tert-butylbicyclophosphorothionate; C087307:1-amino-5-bromouracil