Effect of portacaval anastomosis on glutamine synthetase protein and gene expression in brain, liver and skeletal muscle

Paul Desjardins, K. V. Rama Rao, Adrianna Michalak, Christopher Rose, Roger F. Butterworth

Research output: Contribution to journalArticlepeer-review

75 Scopus citations


The effects of chronic liver insufficiency resulting from end-to-side portacaval anastomosis (PCA) on glutamine synthetase (GS) activities, protein and gene expression were studied in brain, liver and skeletal muscle of male adult rats. Four weeks following PCA, activities of GS in cerebral cortex and cerebellum were reduced by 32% and 37% (p<0.05) respectively whereas GS activities in muscle were increased by 52% (p<0.05). GS activities in liver were decreased by up to 90% (p<0.01), a finding which undoubtedly reflects the loss of GS-rich perivenous hepatocytes following portal-systemic shunting. Immunoblotting techniques revealed no change in GS protein content of brain regions or muscle but a significant loss in liver of PCA rats. GS mRNA determined by semiquantitative RT-PCR was also significantly decreased in the livers of PCA rats compared to sham-operated controls. These findings demonstrate that PCA results in a loss of GS gene expression in the liver and that brain does not show a compensatory induction of enzyme activity, rendering it particularly sensitive to increases in ammonia in chronic liver failure. The finding of a post-translational increase of GS in muscle following portacaval shunting suggests that, in chronic liver failure, muscle becomes the major organ responsible for the removal of excess blood-borne ammonia.

Original languageEnglish (US)
Pages (from-to)273-280
Number of pages8
JournalMetabolic Brain Disease
Issue number4
StatePublished - 1999
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


  • Ammonia
  • Gene expression
  • Glutamine synthetase
  • Hepatic encephalopathy
  • Liver
  • Portacaval anastomosis
  • Skeletal muscle


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