Abstract
This report describes the purification and characterization from rat brain of DBI39-75, a novel, biologically active processing product of diazepam binding inhibitor (DBI). We have shown that DBI39-75 in nM concentrations stimulates pregnenolone synthesis in mitochondria of rat brain. Using cross-linking of 125I-DBI39-75 in steroidogenically active concentrations we have demonstrated for the first time that the DBI fragment has a specific high affinity binding site in rat brain. Displacement of [3H]PK 11195 and [3H]Ro5-4864 by DBI39-75 indicates more complex interaction than the competitive inhibition. Collectively, the data suggest that the function of DBI39-75 is mediated through a mitochondrial receptor complex which includes binding sites for PK 11195 and Ro5-4864.
MeSH terms
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Amino Acid Sequence
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Animals
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Benzodiazepinones / metabolism*
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Binding Sites
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Brain / drug effects
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Brain / metabolism*
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Carrier Proteins / isolation & purification*
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Carrier Proteins / metabolism
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Carrier Proteins / pharmacology
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Chromatography, High Pressure Liquid
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Cross-Linking Reagents
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Diazepam Binding Inhibitor
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Isoquinolines / metabolism*
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Male
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Mitochondria / metabolism
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Molecular Sequence Data
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Neuropeptides / isolation & purification*
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Neuropeptides / metabolism
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Neuropeptides / pharmacology
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Peptide Fragments / isolation & purification*
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology
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Pregnenolone / biosynthesis
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Radioligand Assay
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Rats
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Rats, Sprague-Dawley
Substances
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Benzodiazepinones
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Carrier Proteins
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Cross-Linking Reagents
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Diazepam Binding Inhibitor
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Isoquinolines
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Neuropeptides
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Peptide Fragments
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diazepam binding inhibitor (39-75)
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4'-chlorodiazepam
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Pregnenolone
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PK 11195