Disease relevance of Dbi

• cDNA clones corresponding to the polypeptide that has been shown to be an endogenous diazepam binding inhibitor and may act as a physiological ligand for the benzodiazepine/beta-carboline receptor have been isolated from bacteriophage lambda recombinant libraries from rat hypothalamus, total brain, and liver [1].
• Pregnenolone biosynthesis in C6-2B glioma cell mitochondria: regulation by a mitochondrial diazepam binding inhibitor receptor [2].
• This drug interaction was extended to the level of antiproliferative activity in which DBI was found to potentiate the growth-inhibitory effects of MGBG on murine L1210 leukemia in vivo [3].
• ACBP overexpression in COS-7 or rat hepatoma cells enhanced transactivation of an HNF-4 alpha-dependent luciferase reporter plasmid by 3.2- and 1.6-fold, respectively [4].
• It was once well accepted that liver fatty acid binding protein bound fatty acyl-CoAs, but the recent finding of a novel acyl-CoA binding protein (ACBP) in preparations of L-FABP has challenged the role of FABPs in acyl-CoA metabolism [5].

Psychiatry related information on Dbi

• These results indicate that cerebral DBI is enhanced by psychological stress, which is regulated by central BZD receptors [6].
• Altogether, the present data suggest that Abeta-induced activation of endozepine biosynthesis and release may contribute to astrocyte proliferation associated with Alzheimer's disease [7].
• Mitochondrial diazepam-binding inhibitor receptor complex agonists antagonize dizocilpine amnesia: putative role for allopregnanolone [8].
• Using conditioned place preference (CPP) rat model and in situ hybridization technique, we examined the correlation between opiate dependence and the mRNA expression of DBI [9].

High impact information on Dbi

• In the rat cerebral cortex, DBI immunoreactivity is located in neurons that are not GABAergic (GABA, gamma-aminobutyric acid); in the cerebellum and hippocampus, however, it might be present also in GABAergic neurons [10].
• Luminal DBI levels increased 4-fold [11].
• The amino acid sequence of this peptide was determined to be identical to that of the diazepam-binding inhibitor (DBI) [11].
• Diazepam-binding inhibitor mediates feedback regulation of pancreatic secretion and postprandial release of cholecystokinin [11].
• Infusion of the CCK antagonist MK-329 completely blocked the diazepam binding inhibitor-stimulated amylase secretion [12].

Chemical compound and disease context of Dbi

• DBI and its naturally occurring fragments have been found to be present in high concentrations in C6-2B glioma cells, to compete against specific isoquinolinecarboxamide or 4'-chlorodiazepam binding to mitochondrial recognition sites with high affinity, and to stimulate mitochondrial pregnenolone formation [2].
• Induction of hepatic acyl-CoA-binding protein and liver fatty acid-binding protein by perfluorodecanoic acid in rats. Lack of correlation with hepatic long-chain acyl-CoA levels [13].
• We investigated which EP receptors mediate PGE2-induced hyperthermia by injecting selective EP receptor agonists into the rat lateral cerebral ventricle under unrestrained condition [14].

Biological context of Dbi

• To investigate the regulation of DBI gene expression, three positive clones were isolated from a rat genomic library [15].
• Two other overlapping clones contained a processed DBI pseudogene [15].
• One of them contained a DBI genomic DNA fragment encompassing 4 kb of the 5' untranslated region, the first two exons, and part of the second intron of the DBI gene [15].
• These data suggest that TTN, a natural DBI processing product acting at "Ro 5-4864 preferring" BZ binding site subtypes, might function as a putative neuromodulator of specific GABAA receptor-mediated effects [16].
• Acyl-CoA-binding protein in the rat. Purification, binding characteristics, tissue concentrations and amino acid sequence [17].

Anatomical context of Dbi

• Here we confirm a previous observation that ACBP expression in rodent liver is down-regulated by fasting, and we show that insulin but not glucose is the inducer of ACBP expression in primary rat hepatocytes [18].
• These findings provide evidence that C6-2B cells exhibit a significant steroidogenic activity which resembles that found in peripheral endocrine organs and they suggest that MDRs and DBI are involved in the regulation of glial cell steroidogenesis [2].
• The steroidogenic capability of this cell line and the regulation of pregnenolone production by 4'-chlorodiazepam (4'CD), a specific ligand for the mitochondrial diazepam binding inhibitor (DBI) receptor (MDR), were investigated [19].
• Diazepam-binding inhibitor (DBI)-processing products, acting at the mitochondrial DBI receptor, mediate adrenocorticotropic hormone-induced steroidogenesis in rat adrenal gland [20].
• Both the content of DBI and DBI mRNA increased in the cerebellum and cerebral cortex but failed to change in the hippocampus and striatum of rats receiving this protracted benzodiazepine treatment [21].

Associations of Dbi with chemical compounds

• In addition to high levels of mRNA in various brain regions, RNA blot analysis reveals an abundance of diazepam binding inhibitor mRNA in many peripheral organs (e.g., testes, kidney, liver, and heart) that are known to be rich in peripheral benzodiazepine recognition sites [1].
• Diazepam binding inhibitor (DBI) is a 10-kDa polypeptide that regulates mitochondrial steroidogenesis, glucose-induced insulin secretion, metabolism of acyl-CoA esters, and the action of gamma-aminobutyrate on GABAA receptors [15].
• Isolation and characterization of a rat brain triakontatetraneuropeptide, a posttranslational product of diazepam binding inhibitor: specific action at the Ro 5-4864 recognition site [16].
• By binding with high affinity to the MDR, DBI and one of its processing products--DBI-(17-50)--regulate pregnenolone synthesis and have been suggested to participate in the immediate activation of adrenal steroidogenesis by adrenocorticotropic hormone (ACTH) [20].
• Acute treatment with diazepam did not affect the dynamic state of brain DBI [21].

Regulatory relationships of Dbi

• In addition, somatostatin reduced forskolin-induced endozepine release [22].
• We have recently demonstrated that the endozepine octadecaneuropeptide (ODN) exerts an inhibitory influence on corticotropin-releasing hormone (CRH) mRNA expression [23].
• The present results demonstrate that PACAP stimulates endozepine release through activation of PAC1 receptors coupled to the AC/PKA pathway [24].

Other interactions of Dbi

• Previous studies have demonstrated that gastric mucosa contained high levels of the polypeptide diazepam binding inhibitor, the endogenous ligand of the peripheral-type benzodiazepine receptor (PBR) [25].
• Diazepam binding inhibitor is a potent cholecystokinin-releasing peptide in the intestine [12].
• Physical and functional interaction of Acyl-CoA-binding protein with hepatocyte nuclear factor-4 alpha [4].
• Acyl-CoA-binding protein, a 20-kDa homodimer that exerts many physiological functions, promotes activation of the classic calpain forms, most markedly that of the m-isozyme [26].
• H89 mimicked the inhibitory effect of somatostatin on endozepine secretion [22].

Analytical, diagnostic and therapeutic context of Dbi

• Brain TTN was purified by immunoaffinity chromatography with polyclonal octadecaneuropeptide, DBI 33-50) antibodies coupled to CNBr-Sepharose 4B followed by two reverse-phase HPLC steps [16].
• To test the role of DBI in pancreatic secretion and responses to feeding, we used pancreaticobiliary and intestinal cannula to divert bile-pancreatic juice from anesthetized rats [11].
• Using a perfusion system containing isolated mucosal cells from the proximal intestine of rats, porcine diazepam binding inhibitor 10(-12) M) dose dependently stimulated CCK secretion [12].
• In the present study, we used a sandwich enzyme-linked immunosorbent assay to quantify ACBP concentration in different muscle fiber types [27].
• Time-resolved fluorometry revealed that ACBP-bound parinaroyl-CoAs had high rotational freedom within the single, relatively hydrophobic (epsilon <32), binding site [28].

References