Evidence for the compartmentation of glutamate metabolism in isolated rat retina.

Abstract

Abstract—Glucose is a major precursor of glutamate and related amino acids in the retina of adult rats. 14C from labelled glucose appears to gain access to a large glutamate pool, and the resulting specific activity of glutamate labelled from glucose is always higher than that of glutamine or the other amino acids.Radioactive acetate appeared to label a small glutamate pool. The specific activity of glutamine labelled from acetate relative to that of glutamate was always greater than 1.0. Other precursors of the small glutamate pool were found to include glutamate, aspartate, GABA, serine, leucine and sodium bicarbonate.The level of radioactivity present in retinae incubated with [U‐14C]glucose or [1‐14C]sodium acetate was reduced in the presence of 10−5m‐ouabain. Under these conditions, the relative specific activity of glutamine labelled from [1‐14C]sodium acetate was lowered, but it was raised when [U‐14C]glucose was used as substrate. Ouabain also considerably reduced the synthesis of GABA from [1‐14C]sodium acetate. In all cases ouabain caused a fall in the tissue levels of the amino acids.Aminooxyacetic acid (10−4m) almost completely abolished the labelling of GABA from both [U‐14C]glucose and [1‐14C]sodium acetate, while the RSA of glutamine labelled from the latter substrate was significantly increased. Aminooxyacetic acid raised the tissue concentration of glutamate, but caused a fall in the tissue concentrations of glutamine, aspartate and GABA.The results suggest that there are separate compartments for the metabolism of glutamate in retina and that these can be modified in different ways by different drugs.