169445

Histidine modification with diethyl pyrocarbonate shows heterogeneity of benzodiazepine receptors.

Article date: 1981/6/1

PubMed ID: 169445

Journal name: Proceedings of the National Academy of Sciences of the United States of America (ISSN: 0027-8424)

ABSTRACT

The effect of diethyl pyrocarbonate modification of histidine on the specific binding of [3H]diazepam and its enhancement with muscimol and (+/-)-pentobarbital was investigated. Diethyl pyrocarbonate treatment produced a dose-related inhibition of specific [3H]diazepam binding to rat brain membranes with a maximal inhibition of approximately 40% at 1 mM. Scatchard analysis of the binding data showed that diethyl pyrocarbonate, while having no effect on the affinity (Kd), decreased the binding capacity (Bmax) of diazepam from a control value of 1543 +/- 116 fmol/mg of protein to 789 +/- 79 fmol/mg of protein (mean +/- SD; P less than 0.005; n = 4). Under conditions in which approximately 40% of the diazepam binding sites were modified by diethyl pyrocarbonate treatment, the ability of muscimol and pentobarbital to enhance diazepam binding was not altered. These results suggest that a histidine residue is critical for a part (approximately 40%) of the benzodiazepine binding sites and that there may exist a heterogeneity of benzodiazepine binding sites. Furthermore, these results indicate that perhaps only a portion of the benzodiazepine binding sites are functionally coupled to the gamma-aminobutyric acid receptor-ionophore complex.

Author List: Burch T P, Ticku M K

Publication Types: Journal Article; Research Support, U.S. Gov't, P.H.S.

Substances mentioned in the article: Formates; Receptors, Drug; Receptors, GABA-A; Receptors, Neurotransmitter; Benzodiazepines; Muscimol; Histidine; Pentobarbital; Diethyl Pyrocarbonate; Diazepam;

Mesh terms: Animals; Benzodiazepines/metabolism; Brain; Chemical Phenomena; Chemistry; Diazepam/metabolism; Diethyl Pyrocarbonate/pharmacology; Formates/pharmacology; Histidine; Male; Muscimol/pharmacology; Pentobarbital/pharmacology; Rats; Receptors, Drug/drug effects; Receptors, GABA-A; Receptors, Neurotransmitter/drug effects;

Citations: - 4155790

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