Premium
Subcellular Location and Neuronal Release of Diazepam Binding Inhibitor
Author(s) -
Ferrarese Carlo,
Vaccarino Flora,
Alho Hannu,
Mellstrom Britt,
Costa Erminio,
Guidotti Alessandro
Publication year - 1987
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1987.tb05632.x
Subject(s) - veratridine , depolarization , tetrodotoxin , synaptosome , cerebral cortex , biophysics , biology , percoll , synaptic vesicle , chemistry , neuroscience , biochemistry , centrifugation , central nervous system , sodium , sodium channel , vesicle , organic chemistry , membrane
Diazepam binding inhibitor (DBI), a peptide located in CNS neurons, blocks the binding of benzodiaze‐pines and β‐carbolines to the allosteric modulatory sites of γ‐aminobutyric acid (GABA A ) receptors. Subcellular frac‐tionation studies of rat brain indicate that DBI is compartmentalized. DBI‐like immunoreactivity is highly enriched in synaptosomes obtained by differential centrifugation in isotonic sucrose followed by a Percoll gradient. In synapto‐somal lysate, DBI‐like immunoreactivity is primarily associated with synaptic vesicles partially purified by differential centrifugation and continuous sucrose gradient. Depolarization induced by high K + levels (50 m M ) or veratridine (50 μ M ) released DBI stored in neurons of superfused slices of hypothalamus, hippocampus, striatum, and cerebral cortex. The high K + level‐induced release is Ca 2+ dependent, and the release induced by veratridine is blocked by 1.7 μ M tetrodotoxin. Depolarization released GABA and Met 5 ‐enkephalin‐Arg 6 ‐Phe 7 together with DBI. DBI is also released by veratridine depolarization, in a tetrodotoxin‐sen‐sitive fashion, from primary cultures of cerebral cortical neurons, but not from cortical astrocytes. Depolarization fails to release DBI from slices of liver and other peripheral organs. These data support the view that DBI may be released as a putative neuromodulatory substance from rat brain neurons.