GLUTAMINE STIMULATES GAMMA-AMINOBUTYRIC-ACID SYNTHESIS IN SYNAPTOSOMES BUT OTHER PUTATIVE ASTROCYTE-TO-NEURON SHUTTLE SUBSTRATES DO NOT

GABAergic neurons require a supply of precursor glutamate for gamma-am inobutyric acid (GABA) synthesis to maintain their GABA levels. Becaus e neurons lack the anaplerotic enzymes necessary for net synthesis of glutamate from glucose, they depend on astrocytes to supply compounds that can be metabolized to glutamate and ultimately used for GABA prod uction. To test the effect of putative astrocytic shuttle metabolites on GABA synthesis, we used synaptosomes prepared from substantia nigra , an area rich in GABAergic terminals. The low number of glutamatergic endings in the nigral preparation allows a more accurate measurement of glutamate present in GABAergic endings. GABA synthesis by nigral sy naptosomes was stimulated 3.1-fold when 500 mu M glutamine was added t o the incubation medium. Glutamate amounts also increased. In contrast , the possible precursor metabolites, 2-oxoglutarate (2-OG), malate an d citrate, failed to stimulate GABA synthesis over the rate observed w ith control medium. Unlike malate and citrate, 2-OG reduced the declin e in total glutamate observed when synaptosomes were incubated in cont rol. In contrast to glutamine the production of synaptosomal glutamate from 2-OG, malate, and, citrate is not great enough to stimulate GABA synthesis.