NDLI: Histidine modification with diethyl pyrocarbonate shows heterogeneity of benzodiazepine receptors.

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Histidine modification with diethyl pyrocarbonate shows heterogeneity of benzodiazepine receptors.

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Histidine modification with diethyl pyrocarbonate shows heterogeneity of benzodiazepine receptors.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Burch, T. P. Ticku, M. K.
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.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	6
Volume Number	78
Language	English
Publisher	National Academy of Sciences
Publisher Date	1981-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Benzodiazepines Metabolism Diethyl Pyrocarbonate Pharmacology Formates Receptors, Drug Drug Effects Receptors, Neurotransmitter Animals Brain Chemical Phenomena Chemistry Diazepam Histidine Muscimol Pentobarbital Receptors, GABA-A Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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