Partial chemical characterization of cyclopyrrolones ([3H] suriclone) and benzodiazepines ([3H]flunitrazepam) binding site: differences.
Rat hippocampus membranes were treated with several protein modifying reagents (iodoacetamide, N-ethylmaleimide, tetranitromethane and N-acetylimidazole). The effects of these treatments on the binding sites of cyclopyrrolones ([3H] suriclone), a new chemical family of minor tranquilizers, and benzodiazepines ([3H] flunitrazepam) were investigated. Here we show that both ligands are similarly sensitive to cysteine alkylation: [3H] suriclone and [3H] flunitrazepam binding are reduced by iodoacetamide and slightly increased by N-ethylmaleimide. On the contrary they are clearly differenciated by tyrosine modification: [3H] suriclone binding is not changed whereas [3H] flunitrazepam binding is increased by tetranitromethane and decreased by N-acetylimidazole. Our present findings and published evidence suggest cyclopyrrolones and benzodiazepines bind to distinct sites or to different allosteric forms of the benzodiazepine receptor.
Zundel
J L
JL
Blanchard
J C
JC
Julou
L
L
D000818:Animals; D005033:Ethylmaleimide / Q000494:pharmacology; D005445:Flunitrazepam / Q000378:metabolism*; D006624:Hippocampus / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D007460:Iodoacetamide / Q000494:pharmacology; D008297:Male; D009287:Naphthyridines; D010879:Piperazines / Q000378:metabolism*; D051381:Rats; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*; D013457:Sulfur Compounds; D013774:Tetranitromethane / Q000494:pharmacology; D014316:Tritium
D007093:Imidazoles; D009287:Naphthyridines; D010879:Piperazines; D011963:Receptors, GABA-A; D013457:Sulfur Compounds; D014316:Tritium; D005445:Flunitrazepam; D013774:Tetranitromethane; C037283:suriclone; D005033:Ethylmaleimide; C012160:N-acetylimidazole; D007460:Iodoacetamide