Benzodiazepine agonists protect a histidine residue from modification by diethyl pyrocarbonate whereas propyl beta-carboline does not.
The pH sensitivity of benzodiazepine binding suggests that a histidine residue may be present in, or close to the benzodiazepine binding site. This was confirmed by the selective modification of histidine residues using diethyl pyrocarbonate which was found to block both benzodiazepine and beta-carboline binding. In order to assess whether this histidine residue is located in or adjacent to the benzodiazepine and beta-carboline binding sites, experiments were performed using either benzodiazepine or beta-carboline to protect against diethyl pyrocarbonate treatment. It was found that benzodiazepine agonists, but not propyl beta-carboline protect the benzodiazepine binding sites from diethyl pyrocarbonate modification.
D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D002462:Cell Membrane / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism*; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology*; D005442:Flumazenil / Q000378:metabolism; D005561:Formates / Q000494:pharmacology*; D006639:Histidine; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects / Q000378:metabolism*
D002243:Carbolines; D005561:Formates; D011963:Receptors, GABA-A; C040697:9-propyl-beta-carboline; D005442:Flumazenil; D006639:Histidine; D004047:Diethyl Pyrocarbonate