SELECTIVE-INHIBITION OF GLIAL-CELL METABOLISM INVIVO BY FLUOROCITRATE

The effect of fluorocitrate on glial and neuronal amino acid metabolism was studied. One nmol of fluorocitrate administered intrastriatally in the rat caused a 95% reduction of glutamine formation from [C-14]acetate, a substrate which enters the glial cells selectively. The metabolism of [C-14]glucose which enters neurons, was unaffected by fluorocitrate treatment except for the glutamine formation. This is evidence that fluorocitrate is a selective inhibitor of the glial Krebs' cycle. [C-14]Citrate and 2-oxoglutarate labelled amino acids in a manner similar to [C-14]acetate, which shows that these substrates are taken up and metabolized by glial cells. Differences in the labelling of gamma-aminobutyric acid (GABA) from [C-14]acetate and citrate suggest that astrocytes associated with GABAergic and glutamatergic nerve terminals may differ in their preference for amino acid precursors.