Disease relevance of Bzrp

• Peripheral-type benzodiazepine receptor (PBR) protein was also increased at 6 and 7 days of age in pups exposed to hypoxia from birth [1].
• Peripheral benzodiazepine receptor (PBR) expression increases in small dorsal root ganglion (DRG) sensory neurons after peripheral nerve injury [2].
• In conclusion, our results suggest that enhanced IBP expression, including enhanced PBR ligand binding, such as occurring in untreated C6 glioma cells, may provide a mechanism to increase apoptotic rates of cancer cells [3].
• We examined the biochemical and ultrastructural alterations in rat liver following experimentally induced acute hepatic porphyria, as well as the effects of the administration of a selective PBR ligand, PK 11195 [4].
• Stimulation of mitochondrial benzodiazepine receptors (MBRs), which enhances neurosteroid production, by infusions of an MBR agonist to the VTA enhances lordosis [5].

Psychiatry related information on Bzrp

• Quantitative receptor autoradiography was used to evaluate the density of high-affinity binding sites for the "peripheral-type" benzodiazepine receptor (PTBR) ligand [3H]PK11195 in brain regions of the rat at different stages of pyrithiamine-induced thiamine deficiency encephalopathy, an experimental model of the Wernicke-Korsakoff syndrome (WKS) [6].
• These results suggest that inflammatory responses from activated microglia are damaging to striatal neurons and pharmacological targeting of PBR in microglia may be an effective strategy in protecting neurons in neurological disorders such as Huntington's disease [7].
• Overexpression of the peripheral benzodiazepine receptor (PBR) has been observed in a variety disease states, including glioblastoma, breast cancer, and Alzheimer's disease [8].
• In addition, virtually all stress procedures that cause rapid changes in PBR simultaneously increase the physical activity or metabolic rate of the subjects [9].

High impact information on Bzrp

• Collapse of the mitochondrial membrane potential preceeded PBR-ligand-induced apoptosis [10].
• The selective PBR ligands 1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3-isoquinolinecarboxamide (PK11195) and 4' chlorodiazepam (Ro5-4864), but not the centrally acting benzodiazepine ligand clonazepam, induced dose-dependent apoptosis in HSC [10].
• No apoptosis was induced by PK11195 in parenchymal cells, despite the presence of PBR, and PK11195 had no effect in these cells on Bad phosphorylation and Bcl-2 expression [10].
• Immunoreactive PBR showed a punctate staining and colocalized with mitochondrial manganese-dependent superoxide dismutase and adenine nucleotide translocator 1 [10].
• The 18-kDa protein is labeled by the isoquinoline carboxamide mBzR ligand [3H]PK14105, whereas the 30- and 32-kDa subunits are labeled by the benzodiazepine (Bz) ligands [3H]flunitrazepam and [3H]AHN-086 [11].

Chemical compound and disease context of Bzrp

• Adrenocortical responses to ACTH in neonatal rats: effect of hypoxia from birth on corticosterone, StAR, and PBR [1].
• On the basis of receptor-binding displacement assays in rat brain and glioma cells, 9 had appreciable binding affinity and displaced a prototypical PBR ligand, Ro 5-4864, with IC50 values between 289 and 390 nM [12].
• In the present study, rats received intraperitoneal kainic acid injections, which are known to cause seizures, neurodegeneration, hyperactivity, gliosis, and a fivefold increase in PBR ligand binding density in the hippocampus [13].
• The centrally acting benzodiazepine compounds clonazepam and flumazenil, which have negligible affinities for the MBR, had no effect on ALA-mediated phototoxicity [14].
• Ventral tegmental area (VTA) infusions of the MBR agonist, FGIN 1-27, increase midbrain levels of the progesterone metabolite 5alpha-pregnan-3alpha-ol-20-one (3alpha,5alpha-THP) and lordosis of rats and hamsters [15].

Biological context of Bzrp

• This report describes the cloning of a full length cDNA encoding PKBS, a protein of approximately 17 kDa associated with peripheral-type benzodiazepine binding sites [16].
• The PKBS cDNA was cloned into an eukaryotic expression vector placing it under transcriptional control of the beta-globin promoter and SV40 enhancer [16].
• The peripheral-type benzodiazepine receptor and tumorigenicity: isoquinoline binding protein (IBP) antisense knockdown in the C6 glioma cell line [3].
• We therefore tested the hypotheses that the change in phenotype induced by ACTH was permanent, and that the effects of ACTH were mediated by increased PBR expression [17].
• The MBR gene is comprised of four exons spanning approx. 10 kb [18].

Anatomical context of Bzrp

• Levels of the variant of the neuronal nitric oxide synthase (nNOS) that is restricted to Leydig cells, TnNOS, significantly increased in response to ISO, CRF, and EtOH over the time course of altered StAR/PBR concentrations [19].
• Developmental expression of the peripheral-type benzodiazepine receptor and the advent of steroidogenesis in rat adrenal glands [20].
• Although the precise mechanism whereby cholesterol is transported across the outer mitochondrial membrane is uncertain, a multimeric receptor complex termed the peripheral-type benzodiazepine receptor (PBR) appears essential for this process [20].
• When DRG cells were preconditioned into an active growth state by a prior peripheral nerve injury Ro5-4864 augmented and PK 11195, a PBR antagonist, blocked the injury-induced increased outgrowth [2].
• Recently, we found that high levels of PBR ligand binding in glioma cell lines correlate with in vitro tumorigenicity [3].

Associations of Bzrp with chemical compounds

• However, pretreatment of the rats with N(w)nitro-arginine methylester, which blocked ISO-induced increases in TnNOS, neither restored the T response to human chorionic gonadotropin nor prevented the decreases in StAR and PBR [19].
• This effect appears to be mediated at least in part by an increase in controllers of mitochondrial cholesterol transport (StAR and PBR) and to occur independently of measurable changes in endogenous plasma ACTH [1].
• These studies suggest that PKBS comprises binding domains for benzodiazepines and isoquinoline carboxamides and hence is apparently responsible for the manifestation of peripheral-type benzodiazepine recognition sites [16].
• Cyanogen bromide digestion of purified PKBS yielded several peptide fragments which were subjected to gas-phase sequencing [16].
• Exposure to ACTH, but not saline, for 1 wk significantly increased adrenal mass, the corticosterone response to ACTH, and the expression of PBR protein and mRNA [17].

Regulatory relationships of Bzrp

• A ligand of the mitochondrial benzodiazepine receptor (Ro5-4864) in submicromolar concentrations had an apparent influence on the kinetic behavior of enzymatic coupling of hexokinase and creatine kinase [21].

Other interactions of Bzrp

• Activation of a neural brain-testicular pathway rapidly lowers Leydig cell levels of the steroidogenic acute regulatory protein and the peripheral-type benzodiazepine receptor while increasing levels of neuronal nitric oxide synthase [19].
• GnRH-Ag also reduced, in the CL, the PBR protein/ligand binding, the StAR protein and P450 scc protein and its activity as early as 8 h after the treatment and they remained low compared with those in corresponding sham controls [22].
• Differentiated RGA-1 cells were found to express inhibin alpha- and beta-transcripts, as well as steroidogenic acute regulatory protein and peripheral-type benzodiazepine receptor proteins in a manner reminiscent of steroidogenic functional responses observed in primary differentiated granulosa cells [23].
• Peripheral-type benzodiazepine receptors (PBR) are constituted by three protein components, the isoquinoline binding protein (IBP), the voltage-dependent anion channel (VDAC), and the adenine nucleotide transporter (ANT) [3].
• 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) [24].

Analytical, diagnostic and therapeutic context of Bzrp

• Molecular cloning and expression of cDNA encoding a peripheral-type benzodiazepine receptor [16].
• Immunohistochemistry identified an intense PBR immunoreactivity in the mucous and parietal cells of rat gastric fundus and in the mucous cells of antrum [24].
• Immunoelectron microscopy revealed the mitochondrial localization of PBR in these cells [24].
• In another series of experiments, we used semipurified Leydig cell preparations to measure StAR, PBR, P450scc, and TnNOS by Western blot analysis [25].
• Purified preparations of PKBS exhibited a single band with a Mr of approximately 17,000 when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by silver-staining or autoradiographic detection [26].

References