Overestimation of serum concentrations of γ-aminobutyric acid in patients with hepatic encephalopathy by the γ-aminobutyric acid-radioreceptor assay
✍ Scribed by Peter Ferenci; Josef Ebner; Christof Zimmermann; Christian Kikuta; Erich Roth; Dieter Häussinger
- Publisher
- John Wiley and Sons
- Year
- 1988
- Tongue
- English
- Weight
- 492 KB
- Volume
- 8
- Category
- Article
- ISSN
- 0270-9139
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✦ Synopsis
Sera of patients with hepatic encephalopathy strongly inhibit the specific binding of y-aminobutyric acid to synaptic membranes. In a previous study, this inhibition of specific y-aminobutyric acid binding was attributed to y-aminobutyric acid itself, and it was assumed that serum y-aminobutyric acid is increased 5-to 30-fold in patients with hepatic encephalopathy. The findings of that study, however, were not confirmed by other analytical methods. Therefore, the validity of the y-aminobutyric acid-radioreceptor assay was tested. In view of the increased serum concentrations of several amino acids in hepatic encephalopathy, the effects of L-a-amino acids on the assay were studied. Five amino acids inhibited specific y-aminobutyric acid binding at a concentration of 0.5 mM or lower: glutamine; glutamate; taurine; proline, and OH-proline. Equimolar amounts of aminooxyacetate prevented the inhibition of specific y-aminobutyric acid binding by glutamine and glutamate but had no effect on that of y-aminobutyric acid, taurine, proline and OH-proline. Aminooxyacetate had no effect on specific y-aminobutyric acid binding itself. The inhibitory activity of a serum sample from a patient with hepatic encephalopathy was inhibited by 0.5 m M aminooxyacetate. The y-aminobutyric acid binding inhibitory activity of a serum sample of a patient with hepatic encephalopathy was purified by gel chromatography and contained several amino acids at concentrations of about 0.1 mM, 3.5 m M glutamine but no detectable yaminobutyric acid. Accordingly, the y-aminobutyric acid binding inhibitory activity is not mediated by y-aminobutyric acid alone and is most likely due to glutamine. Thus, using the y-aminobutyric acid-radioreceptor assay serum, "true y-aminobutyrie acid" concentrations in patients with hepatic encephalopathy were overestimated.