Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Using quantitative receptor radioautography, binding sites for the 'peripheral-type' benzodiazepine receptor ligand [3H]PK 11195 were studied in rats 4 week after end-to-side portacaval anastomosis and in sham-operated controls. Portacaval anastomosis resulted in region-selective increases in density of [3H]PK 11195 binding sites in cerebellum, pons greater than thalamus, cerebral cortex greater than hippocampus greater than striatum. Possible mechanisms implicated in these changes include (i) the action of endogenous ligands for the mitochondrial benzodiazepine receptor such as octadecaneuropeptide and (ii) neurotoxic actions of ammonia. In view of the proposed role of these receptors as modulators of intermediary metabolism and neurosteroid biosynthesis, such changes could contribute to the neurochemical mechanisms responsible for portal-systemic encephalopathy.
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PMID:Increased densities of binding sites for the 'peripheral-type' benzodiazepine receptor ligand [3H]PK 11195 in rat brain following portacaval anastomosis. 132 70

Using RT-PCR, gene expression of the peripheral-type benzodiazepine receptor isoquinoline carboxamide-binding protein (PTBR-IBP) was studied in the frontal cortex of rats four weeks following end-to-side portacaval anastomosis, an experimental animal model of hepatic encephalopathy, or sham operation. Portacaval anastomosis resulted in increased expression of PTBR-IBP in frontal cortex and in a concomitant increase in densities (Bmax) of binding sites for the PTBR ligand [3H]PK11195. In view of the findings that the PTBR modulates the synthesis of neurosteroids with high affinity for excitatory and inhibitory neurotransmitter systems in brain, increased expression of these receptors could be implicated in the pathogenesis of hepatic encephalopathy.
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PMID:Increased expression of the peripheral-type benzodiazepine receptor-isoquinoline carboxamide binding protein mRNA in brain following portacaval anastomosis. 920 58

An increasing body of evidence supports the notion that activation of astrocytic (peripheral-type) benzodiazepine receptors contributes to the pathogenesis of the central nervous system symptoms which are characteristic of portal-systemic encephalopathy (PSE). Binding site densities for the PTBR ligand [3H-PK11195] are increased in autopsied brain tissue from PSE patients as well as in the brains of animals with experimental chronic liver failure. In the case of the animal studies, increased PTBR sites resulted from increased PTBR gene expression. Exposure of cultured astrocytes to ammonia or manganese (two neurotoxic agents which under normal circumstances are removed by the hepatobiliary system and which are found to accumulate in brain in PSE) results in increased densities of [3H-PK11195] binding sites. Activation of PTBR is known to result in increased cholesterol uptake and increased synthesis in brain of neurosteroids some of which have potent positive allosteric modulator properties on the GABA-A receptor system. Accumulation of such substances in the brain in chronic liver failure could explain the neural inhibition characteristics of PSE.
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PMID:The astrocytic ("peripheral-type") benzodiazepine receptor: role in the pathogenesis of portal-systemic encephalopathy. 1073 8

Increased levels of brain ammonia occur in both congenital and acquired hyperammonemic syndromes including hepatic encephalopathy, fulminant hepatic failure, Reye's syndrome and congenital urea cycle disorders. In addition to its effect on neurotransmission and energy metabolism, ammonia modulates the expression of various genes including the astrocytic "peripheral-type" benzodiazepine (or omega 3) receptor (PTBR). Increased expression of the isoquinoline carboxamide binding protein (IBP), one of the components of the PTBR complex, is observed in brain and peripheral tissues following chronic liver failure as well as in cultured astrocytes exposed to ammonia. Increased densities of binding sites for the PTBR ligand [3H]-PK11195 are also observed in these conditions as well as in brains of animals with acute liver failure, congenital urea cycle disorders and in patients who died in hepatic coma. The precise role of PTBR in brain function has not yet fully elucidated, but among other functions, PTBR mediates the transport of cholesterol across the mitochondrial membrane and thus plays a key role in the biosynthesis of neurosteroids some of which modulate major neurotransmitter systems such as the gamma-aminobutyric acid (GABA(A)) and glutamate (N-methyl-D-aspartate (NMDA)) receptors. Activation of PTBR in chronic and acute hyperammonemia results in increased synthesis of neurosteroids which could lead to an imbalance between excitatory and inhibitory neurotransmission in the CNS. Preliminary reports suggest that positron emission tomography (PET) studies using [11C]-PK11195 may be useful for the assessment of the neurological consequences of chronic liver failure.
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PMID:The "peripheral-type" benzodiazepine (omega 3) receptor in hyperammonemic disorders. 1202 Jun 11

Hepatic encephalopathy (HE) is a serious neuropsychiatric complication of liver failure, characterized neuropathologically by astrocyte swelling, microglial activation and Alzheimer Type II astrocytosis. Molecular studies in HE brain reveal altered expression of genes coding for key astroglial proteins including early losses of expression of GFAP and the glutamate transporter EEAT-2 with concomitant increases of the astrocytic/microglial mitochondrial benzodiazepine receptor (MBR). Decreased expression of EAAT-2 results in decreased glutamate transport and impaired cycling of glutamate-glutamine between astrocytes and neurons, as well as increased extracellular glutamate, activation of the NMDA receptor-mediated cGMP-NO signal transduction pathway, and nitration of tyrosine residues on key astroglial proteins such as glutamine synthetase (GS) and the MBR. GS is uniquely responsible for the removal of excess ammonia in brain. Ammonia-induced activation of MBR in astrocytes and/or microglia results in stimulation of the synthesis of neurosteroids such as allopregnanolone with positive allosteric GABA-A receptor neuromodulatory properties. Allopregnanolone concentrations are increased up to 7-fold in HE brain. Attenuation of microglial activation by minocycline results in a delay in onset of HE and prevents brain edema in liver failure. Mild hypothermia is likewise beneficial in acute liver failure resulting in normalization of extracellular brain glutamate and prevention of oxidative/nitrosative stress in experimental animals with HE resulting from either ischemic or toxic liver injuries.
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PMID:Altered glial-neuronal crosstalk: cornerstone in the pathogenesis of hepatic encephalopathy. 2035 May 77