Diethylpyrocarbonate modification of benzodiazepine receptors from calf cerebral cortex

Sherman-Gold, Rivka; Dudai, Yadin

doi:10.1007/bf00963925

Cited by 10 publications

(3 citation statements)

References 19 publications

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“…Differences in species or in membrane preparations and the "unburying" effect of solubilization on a tyrosine residue (Glazer, 1976) might explain the differences. While this manuscript was in preparation, another report of the same authors has been published (Sherman-Gold and Dudai, 1983). On the basis of the pH profile of the DEP reaction, they suggest that DEP might also modify a tyrosine residue instead of histidine.…”

Section: Bz Binding Sitesmentioning

confidence: 89%

Characterization of γ‐Aminobutyric Acid‐Benzodiazepine Receptor Complexes by Protection Against Inactivation by Group‐Specific Reagents

Maksay

Ticku

1984

Journal of Neurochemistry

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The chemical topography of the gamma-aminobutyric acid (GABA) and benzodiazepine (BZ) receptors was investigated in a thoroughly washed cortical membrane preparation of the rat. Chemical modification by several amino- and tyrosyl-selective reagents and the protection from it by direct and allosteric ligands of the GABA-BZ receptor complex were used to identify the residues at the binding sites. Inhibition of specific GABA binding by p-diazobenzenesulfonic acid (DSA), tetranitromethane (TNM), and N-acetylimidazole and the selective and complete protection from it by GABA and muscimol suggest the presence of a tyrosine residue at the GABAA site. TNM, like DSA, selectively decreased the number of the low-affinity GABA receptors, and this could be completely protected only by GABA concentrations that can saturate the low-affinity sites. TNM pretreatment also abolished the muscimol enhancement of [3H]diazepam binding, which suggests that the low-affinity GABA receptor sites are responsible for this enhancement. Inhibition of GABA binding by pyridoxal-5-phosphate (PLP) and the selective protection by GABA and muscimol support the presence of a lysine residue at the GABAA receptor site. Complete and selective protection from diethylpyrocarbonate (DEP) inhibition of [3H]diazepam binding by flurazepam suggests the presence of a histidine residue at the BZ site. Flurazepam selectively protected from inhibition of [3H]diazepam binding by N-bromosuccinimide and N-acetylimidazole, but not that by DSA and TNM, which does not allow a unanimous conclusion regarding the presence of tyrosine or tryptophan residues at the BZ site.

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Section: Bz Binding Sitesmentioning

confidence: 89%

Characterization of γ‐Aminobutyric Acid‐Benzodiazepine Receptor Complexes by Protection Against Inactivation by Group‐Specific Reagents

Maksay

Ticku

1984

Journal of Neurochemistry

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“…Pretreatment of membranes with DEP inhibits benzodiazepine binding in a dose-dependent manner (Burch et al, 1983;Sherman-Gold and Dudai, 1983). Moreover, the rate of the inhibition is pH dependent (Sherman-Gold and Dudai, 1983;Maksay and Ticku, 1984;Lambolez et al, 1989 Fig.…”

Section: Resultsmentioning

confidence: 99%

Effect of Diethyl Pyrocarbonate Modification of Benzodiazepine Receptors on [³H]Ro 15‐4513 Binding

Uusi‐Oukari

1992

Journal of Neurochemistry

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The effects of treatment of brain membranes with diethyl pyrocarbonate (DEP), a histidine-modifying reagent, on the binding of 3H-labeled Ro 15-4513 (ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo[1,5-a]- [1,4]benzodiazepine-3-carboxylate) and [3H]diazepam were compared. DEP pretreatment produced a dose-dependent decrease in [3H]diazepam binding, whereas low DEP concentrations enhanced the binding of [3H]Ro 15-4513. These effects were reversed by incubation with hydroxylamine after the treatment. The enhancement of [3H]Ro 15-4513 binding was due to an increase in the affinity of the binding sites (KD), without any effect on binding capacity (Bmax). The enhancement was perceived in cerebral cortical, cerebellar, and hippocampal membranes. DEP treatment decreased the displacement of [3H]Ro 15-4513 binding by diazepam and FG 7142 (N-methyl-beta-carboline-3-carboxamide) but not by Ro 15-4513 and Ro 19-4603 (tert-butyl-5,6-dihydro-5-methyl-6-oxo-4H-imidazol[1,5- a]thieno[2,3-f][1,4]diazepine-3-carboxylate). Although the stimulating effect of gamma-aminobutyric acid (GABA) on [3H]-diazepam binding was not affected by DEP treatment, such treatment reduced the inhibitory effect of GABA on [3H]Ro 15-4513 binding. The enhancement of [3H]Ro 15-4513 binding was observed in membranes pretreated with DEP in the presence of flunitrazepam, whereas such pretreatment reduced significantly the inhibitory effect of DEP on [3H]-diazepam binding.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…This action of DEP has been attributed to modification of either a histidine or a tyrosine residue [5,6].…”

mentioning

confidence: 99%

Benzodiazepine agonists protect a histidine residue from modification by diethyl pyrocarbonate whereas propyl β‐carboline does not

Lambolez¹,

Rossier²

1987

FEBS Letters

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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 β‐carboline binding. In order to assess whether this histidine residue is located in or adjacent to the benzodiazepine and β‐carboline binding sites, experiments were performed using either benzodiazepine or β‐carboline to protect against diethyl pyrocarbonate treatment. It was found that benzodiazepine agonists, but not propyl β‐carboline protect the benzodiazepine binding sites from diethyl pyrocarbonate modification.

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Diethylpyrocarbonate modification of benzodiazepine receptors from calf cerebral cortex

Cited by 10 publications

References 19 publications

Characterization of γ‐Aminobutyric Acid‐Benzodiazepine Receptor Complexes by Protection Against Inactivation by Group‐Specific Reagents

Characterization of γ‐Aminobutyric Acid‐Benzodiazepine Receptor Complexes by Protection Against Inactivation by Group‐Specific Reagents

Effect of Diethyl Pyrocarbonate Modification of Benzodiazepine Receptors on [³H]Ro 15‐4513 Binding

Benzodiazepine agonists protect a histidine residue from modification by diethyl pyrocarbonate whereas propyl β‐carboline does not

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Diethylpyrocarbonate modification of benzodiazepine receptors from calf cerebral cortex

Cited by 10 publications

References 19 publications

Characterization of γ‐Aminobutyric Acid‐Benzodiazepine Receptor Complexes by Protection Against Inactivation by Group‐Specific Reagents

Characterization of γ‐Aminobutyric Acid‐Benzodiazepine Receptor Complexes by Protection Against Inactivation by Group‐Specific Reagents

Effect of Diethyl Pyrocarbonate Modification of Benzodiazepine Receptors on [3H]Ro 15‐4513 Binding

Benzodiazepine agonists protect a histidine residue from modification by diethyl pyrocarbonate whereas propyl β‐carboline does not

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Effect of Diethyl Pyrocarbonate Modification of Benzodiazepine Receptors on [³H]Ro 15‐4513 Binding