RGD Reference Report - Glutamate decarboxylase inhibition and vitamin B6 metabolism in brain of cirrhotic rats chronically treated with carbon tetrachloride. - Rat Genome Database

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Glutamate decarboxylase inhibition and vitamin B6 metabolism in brain of cirrhotic rats chronically treated with carbon tetrachloride.

Authors: Diaz-Munoz, M  Tapia, R 
Citation: Diaz-Munoz M and Tapia R, J Neurosci Res. 1988 Jul;20(3):376-82.
RGD ID: 2303021
Pubmed: PMID:3225873   (View Abstract at PubMed)
DOI: DOI:10.1002/jnr.490200311   (Journal Full-text)

In a previous work we found that the activity of glutamate decarboxylase (GAD), the enzyme responsible for the synthesis of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), is decreased in comatose cirrhotic rats after chronic treatment with CCl4. In the present report we studied the participation of pyridoxal phosphate in the inhibition of GAD, as well as the concentration of this coenzyme and the activity of its synthesizing enzyme, pyridoxal kinase, in the brain of the cirrhotic rats. Furthermore, cirrhotic animals were treated with three inhibitors of GAD, and the effects of such treatment were compared to those of ammonium. Liver failure resulted in a 25% inhibition of GAD activity when measured in the absence of added pyridoxal phosphate. Treatment with the GAD inhibitors thiosemicarbazide or 3-mercaptopropionic acid enhanced this inhibition and produced convulsions at a dose that had no behavioral effects in control rats. Treatment with ammonia resulted in a comatose state and in a 25-40% inhibition of GAD. Both pyridoxal kinase activity and pyridoxal phosphate levels were found to be decreased by 15-20% in the brain of the cirrhotic rats. We concluded that chronic liver failure results in a decreased pyridoxal phosphate and GABA synthesis in brain, with a consequent diminished efficiency of GABAergic neurotransmission; these effects are probably related to the manifestations of neuronal hyperexcitability that are frequently seen in human hepatic encephalopathy.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PDXKHumanExperimental Liver Cirrhosis  ISOPdxk (Rattus norvegicus)protein:decreased expression:brainRGD 
PdxkRatExperimental Liver Cirrhosis  IEP protein:decreased expression:brainRGD 
PdxkMouseExperimental Liver Cirrhosis  ISOPdxk (Rattus norvegicus)protein:decreased expression:brainRGD 

Objects Annotated

Genes (Rattus norvegicus)
Pdxk  (pyridoxal kinase)

Genes (Mus musculus)
Pdxk  (pyridoxal (pyridoxine, vitamin B6) kinase)

Genes (Homo sapiens)
PDXK  (pyridoxal kinase)


Additional Information