Reduction of brain taurine: Effects on neurotoxic and metabolic actions of kainate.

The effects of chronic administration of 2-guanidinoethane sulfonic acid on the levels of intra- and extracellular amino acids in the rat hippocampus were studied. The tissue content of taurine was selectively reduced by almost one third after 9 days of peroral administration of 1% 2-guanidinoethane sulfonate. Extracellular levels of amino acids were monitored with the brain microdialysis method. The taurine concentration in the extracellular fluid was depressed in relation to the decrease in intracellular taurine. Unexpectedly, extracellular (but not intracellular) glutamate was doubled in 2-guanidinoethane sulfonate treated animals. The kainic acid evoked release of taurine was suppressed in the 2-guanidinoethane sulfonate group, whereas the kainate stimulated efflux of glutamate was elevated after 2-guanidinoethane sulfonate administration. The acute metabolic effects of kainate were studied by measuring the efflux of the adenosine triphosphate breakdown products hypoxanthine, xanthine, inosine and adenosine. No differences were found between control and 2-guanidinoethane sulfonate treated rats with respect to basal or kainic acid evoked release of purine catabolites. Also, the neuronal loss caused by kainate injection into the hippocampus was not modified by 2-guanidinoethane sulfonate treatment, suggesting that endogenous taurine does not affect these responses. We conclude that chronic administration of 2-guanidinoethane sulfonate does not sensitize central neurons to the metabolic and toxic actions of kainate.