A Regional Study of 4‐Aminobutyrate Metabolism and Amino Acid Levels in Rat Brain Following Chronic Oral Administration of Ethanolamine O‐Sulphate

Abstract

Ethanolamine O-sulphate (EOS) dissolved in the drinking water (5 mg . ml(-1) was administered ad libitum to rats for 26 days. At the end of this period, glutamate decarboxylase (GAD) and GAA-transaminase (GABA-T) activities, 4-aminobutyrate (GABA) concentration, and the levels of six other amino acids were measured in various brain regions. Significant inhibition of GABA-T accompanied by significant increases in GABA content were observed throughout the brain, although the magnitudes of these effects varied according to region. GAD activity was significantly reduced in most brain regions, although this effect was apparently not related to cofactor availability or the direct actions of EOS or increased GABA concentration. Glutamine levels were significantly reduced to approximately 72% of control values in all brain regions. Aspartate levels were significantly reduced to approximately 84% of control values in all regions except the striatum and cerebellum. Minor changes in other amino acid levels were also detected. These neurochemical changes which accompanied the primary effect of EOS on GABA-T are discussed in terms of indirect secondary metabolic changes rather than nonspecific enzyme inhibition by EOS.

A rapid assay for neurotransmitter amino acids, aspartate, glutamate, glycine, taurine and ?-aminobutyric acid in the brain by high-performance liquid chromatography with electrochemical detection

“…It is noteworthy that the lower pH dramatically shortened the GABA elution, but produced impairment of clear separation of the Asp and Glu peaks. Gln is not a neurotransmitter but an interesting amino acid that is not only a precursor but also a metabolite of Glu (Fletcher and Fowler, 1982). Thus, determination of Gln could offer some additional information on changes in Glu and GABA levels.…”

Development of the γ‐Aminobutyric Acid Neurotransmitter System in the Rat Cerebral Cortex During Repeated Administration of the GABA‐Transaminase Inhibitor Ethanolamine O‐Sulphate

“…The most likely explanation of the greater effect on GAD activity is that feedback suppression is more sensitive in the neonate, when enzyme synthesis is rapid, than in the adult, when enzyme synthesis is maintaining the steady-state level of enzyme. Although EOS is likely to penetrate the neonatal brain more easily than the adult brain, a greater accumulation of EOS is unlikely to explain these results since almost complete inhibition of cortical GABA-T activity occurs in the adult at the dose of EOS used (Fletcher and Fowler, 1982).…”