Metabolism and Brain Uptake of γ‐Aminobutyric Acid in Galactosamine‐Induced Hepatic Encephalopathy in Rats

Abstract

Kinetic studies of [3H]GABA after an i.v. injection were performed in normal rats and in rats with severe degree of hepatic encephalopathy due to fulminant hepatic failure induced by galactosamine. Plasma and brain GABA levels, and GABA and glutamic acid decarboxylase activity were studied in some brain areas. After i.v. injection, [3H]GABA disappeared very rapidly in the blood of normal rats, with a prompt increase of 3H metabolites. In comatose rats, a delayed disappearance of [3H]GABA was paralleled by a lower amount of metabolites, indirectly indicating a peripheral decrease of GABA-transaminase activity. The amount of [3H]GABA in brain was lightly but constantly lower in comatose rats than in controls, indicating that the change in permeability of the blood-brain barrier in hepatic encephalopathy does not affect the [3H]GABA uptake of the brain. The assay of endogenous GABA in blood, whole brain and brain areas did not show any significant difference in any of the 2 groups. The finding that glutamic acid decarboxylase activity in brain was reduced, together with the indirect evidence of a reduction in GABA-transaminase, may account for the steady state of GABA in hepatic encephalopathy. The reduction in glutamic acid decarboxylase activity favors a functional derangement at the GABAergic nerve terminals in this pathological condition.