Hyperammonemia causes altered protein phosphorylation in astrocytes.

Treatment of primary astrocyte cultures with ammonium chloride for one day prior to phosphoprotein labeling resulted in a reduction in phosphate incorporation in a 66-kDa protein. Increasing ammonium chloride concentrations (2, 5, and 10 mM) led to greater reductions in phosphate incorporation in this band. The specificity of the effect was indicated by the lack of change in phosphate incorporation in 7 other protein bands. These results indicate that protein phosphorylation can be affected by pathophysiological concentrations of ammonia and suggest that altered protein phosphorylation may be related to the pathogenesis of disorders such as hepatic encephalopathy and Reye's syndrome where ammonia has been implicated as an important etiological factor.