gamma-Aminobutyric acid and pentobarbital enhance 2-[3H]oxoquazepam binding to type I benzodiazepine recognition sites in rat and human brain.
2-Oxoquazepam (2oxoquaz) is a novel benzodiazepine which shows preferential affinity for type I benzodiazepine recognition sites. In the present study, we analyzed the effect of gamma-aminobutyric acid (GABA), pentobarbital, and chloride ions on [3H]2oxoquaz and [3H]flunitrazepam ( [3H]FNT) binding to membrane preparations from rat and human brain. GABA stimulated [3H]-2oxoquaz and [3H]FNT binding in a concentration-dependent manner. The maximal enhancement produced by GABA on [3H]2oxoquaz binding was higher than that produced on [3H]FNT binding in both rat and human tissues. In the rat brain, the effect of GABA on [3H]2oxoquaz was similar throughout different brain areas, whereas the effect on [3H]FNT binding was lower in the cerebral cortex and hippocampus than in the cerebellum. Moreover, both [3H]2oxoquaz and [3H]FNT binding were stimulated by chloride ions and pentobarbital. The results are consistent with the hypothesis that type I benzodiazepine recognition sites are linked functionally to the GABA recognition site and the chloride ionophore.
Corda
M G
MG
Department of Experimental Biology, University of Cagliari, Italy.
Giorgi
O
O
Longoni
B
B
Ongini
E
E
Barnett
A
A
Montaldo
S
S
Biggio
G
G
D000328:Adult; D000818:Animals; D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; D001570:Benzodiazepinones / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D004357:Drug Synergism; D005260:Female; D005445:Flunitrazepam / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000145:classification / Q000378:metabolism*; D014316:Tritium; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D014151:Anti-Anxiety Agents; D001570:Benzodiazepinones; D002712:Chlorides; D011963:Receptors, GABA-A; D014316:Tritium; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam; C039103:2-oxoquazepam; D010424:Pentobarbital