Premium
Overestimation of serum concentrations of γ‐aminobutyric acid in patients with hepatic encephalopathy by the γ‐aminobutyric acid‐radioreceptor assay
Author(s) -
Ferenci Peter,
Ebner Josef,
Zimmermann Christof,
Kikuta Christian,
Roth Erich,
Häussinger Dieter
Publication year - 1988
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840080114
Subject(s) - aminobutyric acid , taurine , glutamine , proline , amino acid , biochemistry , chemistry , glutamic acid , hepatic encephalopathy , glycine , glutamate receptor , gamma aminobutyric acid , medicine , receptor , cirrhosis
Sera of patients with hepatic encephalopathy strongly inhibit the specific binding of γ‐aminobutyric acid to synaptic membranes. In a previous study, this inhibition of specific γ‐aminobutyric acid binding was attributed to γ‐aminobutyric acid itself, and it was assumed that serum γ‐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 γ‐aminobutyric acid‐radioreceptor assay was tested. In view of the increased serum concentrations of several amino acids in hepatic encephalopathy, the effects of L‐α‐amino acids on the assay were studied. Five amino acids inhibited specific γ‐aminobutyric acid binding at a concentration of 0.5 m M or lower: glutamine; glutamate; taurine; proline, and OH‐proline. Equimolar amounts of amino‐oxyacetate prevented the inhibition of specific γ‐aminobutyric acid binding by glutamine and glutamate but had no effect on that of γ‐aminobutyric acid, taurine, proline and OH‐proline. Aminooxyacetate had no effect on specific γ‐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 γ‐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 m M , 3.5 m M glutamine but no detectable γ‐aminobutyric acid. Accordingly, the γ‐aminobutyric acid binding inhibitory activity is not mediated by γ‐aminobutyric acid alone and is most likely due to glutamine. Thus, using the γ‐aminobutyric acid‐radioreceptor assay serum, “true γ‐aminobutyric acid” concentrations in patients with hepatic encephalopathy were overestimated.