Plasma GABA-like activity in rats with hepatic encephalopathy is due to GABA and taurine.
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 mumol/L final assay concentration). The concentration of taurine that resulted in 50% inhibition (final assay concentration) was 158 mumol/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.(ABSTRACT TRUNCATED AT 250 WORDS)
Maddison
J E
JE
Department of Veterinary Clinical Sciences, University of Sydney, N.S.W., Australia.
Leong
D K
DK
Dodd
P R
PR
Johnston
G A
GA
D000818:Animals; D001667:Binding, Competitive; D002851:Chromatography, High Pressure Liquid; D005971:Glutamates / Q000378:metabolism; D018698:Glutamic Acid; D005973:Glutamine / Q000378:metabolism; D006501:Hepatic Encephalopathy / Q000097:blood*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000378:metabolism*; D013654:Taurine / Q000097:blood* / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D005680:gamma-Aminobutyric Acid / Q000097:blood* / Q000378:metabolism
D005971:Glutamates; D011963:Receptors, GABA-A; D005973:Glutamine; D013654:Taurine; D018698:Glutamic Acid; D014443:Tyrosine; D005680:gamma-Aminobutyric Acid