Diethylpyrocarbonate modification of benzodiazepine receptors from calf cerebral cortex.
Diethylpyrocarbonate (DEP), an amino acid modifying reagent, causes complete inactivation of particulate and deoxycholate-solubilized benzodiazepine-receptors from calf cerebral cortex. No heterogeneity was observed in DEP-sensitivity of the receptors. Protection from DEP-induced inactivation was provided by the centrally active benzodiazepines, diazepam and nitrazepam, but not by the peripherally active Ro5-4864, suggesting that DEP modifies a residue which is essential for the central actions of benzodiazepines. GABA did not protect against inactivation or influence the protection afforded by diazepam, indicating that the DEP-modifiable residue is independent of GABA binding sites, or that GABA binding sites are also sensitive to DEP. DEP-induced inactivation of benzodiazepine-receptors proceeds much faster at pH 10.1 than at pH 8.1 or 6.0, indicating the modification of a high pKa side group, possibly the phenol of a tyrosyl residue. This postulation is in accord with our previous findings with the modifying reagents tetranitromethane and N-acetylimidazole.
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D002540:Cerebral Cortex / Q000378:metabolism*; D004047:Diethyl Pyrocarbonate / Q000494:pharmacology*; D005445:Flunitrazepam / Q000378:metabolism; D005561:Formates / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D008566:Membranes / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A
D005561:Formates; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D005445:Flunitrazepam; D004047:Diethyl Pyrocarbonate