Barbiturate recognition site on the GABA/benzodiazepine receptor complex is distinct from the picrotoxinin/TBPS recognition site.
The cage convulsant [35S]tert-butylbicyclophosphorothionate [( 35S]TBPS) labels a presumed sedative-convulsant receptor complex. The relative potencies of barbiturates in competing for [35S]TBPS binding parallels their potencies in enhancing benzodiazepine receptor binding. Barbiturates inhibit [35S]TBPS binding in a complex, mixed competitive fashion, leading to a decrease in both the apparent affinity of TBPS for its sites and the apparent number of TBPS sites. All of the barbiturates examined markedly accelerate the dissociation of [35S]TBPS from its recognition sites, while picrotoxinin does not affect the dissociation. These results suggest that the barbiturate and picrotoxinin/TBPS recognition sites are distinct but allosterically linked.
D000495:Allosteric Site; D000818:Animals; D001463:Barbiturates / Q000494:pharmacology*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds / Q000378:metabolism*; D002540:Cerebral Cortex / Q000378:metabolism*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects* / Q000378:metabolism
D001463:Barbiturates; D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D001952:Bridged-Ring Compounds; D011963:Receptors, GABA-A; C037480:picrotoxinin receptor; C037476:tert-butylbicyclophosphorothionate