Plasma gaba-like activity in rats with hepatic encephalopathy is due to gaba and taurine

Authors

  • Jill E. Maddison,

    Corresponding author
    1. Department of 1Veterinary Clinical Sciences and 2Department of Pharmacology, University of Sydney, N. S. W. 2006, Australia and 3Clinical Research Centre, Royal Brisbane Hospital Foundation, Qld. 4029 Australia
    • Department of Veterinary Clinical Sciences, University of Sydney, N. S. W. 2006, Australia
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  • Dorothy K. Leong,

    1. Department of 1Veterinary Clinical Sciences and 2Department of Pharmacology, University of Sydney, N. S. W. 2006, Australia and 3Clinical Research Centre, Royal Brisbane Hospital Foundation, Qld. 4029 Australia
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  • Peter R. Dodd,

    1. Department of 1Veterinary Clinical Sciences and 2Department of Pharmacology, University of Sydney, N. S. W. 2006, Australia and 3Clinical Research Centre, Royal Brisbane Hospital Foundation, Qld. 4029 Australia
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  • Graham A. R. Johnston

    1. Department of 1Veterinary Clinical Sciences and 2Department of Pharmacology, University of Sydney, N. S. W. 2006, Australia and 3Clinical Research Centre, Royal Brisbane Hospital Foundation, Qld. 4029 Australia
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Abstract

Significant discrepancy exists between radioreceptor and high-performance liquid chromatographic estimates of plasma GABA concentrations in animal models of hepatic encephalopathy. A possible explanation for this discrepancy is the presence in plasma of a substance that can inhibit [3H]-GABA binding but is not GABA itself. The aim of this study was to determine whether any of the amino acids that are increased in the plasma of animal models of acute and chronic hepatic encephalopathy (glutamine, glutamate, phenylalanine, tyrosine, citrulline and taurine) can significantly inhibit [3H]-GABA binding and contribute to the GABA-like activity of plasma aliquots.

At final assay concentrations equivalent to plasma concentrations found in hepatic encephalopathy, only taurine was found to significantly inhibit [3H]-GABA binding to whole rat brain synaptosomal membranes (36% inhibition at 30 μmol/L final assay concentration). The concentration of taurine that resulted in 50% inhibition (final assay concentration) was 158 μmol/L, corresponding to a plasma concentration of 1.58 mmol/L. Taurine inhibition of [3H]-GABA binding was competitive because the receptor density was unaltered, but the receptor affinity decreased with increasing concentration of taurine.

Plasma GABA-like activity (determined by radioreceptor assay) and plasma GABA and taurine concentrations (determined by high-performance liquid chromatography) were measured in 18 rats with acute or chronic hepatic encephalopathy and 9 control rats. Plasma GABA-like activity and plasma GABA and taurine concentrations were significantly increased in rats with hepatic encephalopathy compared with control rats.

A comparison of the percent inhibition of [3H]-GABA binding expected by known concentrations (determined by high-performance liquid chromatography) of taurine and GABA in each plasma sample indicated that the inhibition of [3H]-GABA binding by plasma aliquots could be entirely attributed to the presence of GABA and taurine in plasma. Therefore the plasma “GABA-like factor” in animal models of hepatic encephalopathy is taurine. The implications of this finding to the pathogenesis of hepatic encephalopathy are unknown at present.

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