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-aminobutyric acid (GABA) synthesis to maintain their GABA levels. Because 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 production. 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 synaptosomes was stimulated 3.1-fold when 500 microM glutamine was added to the incubation medium. Glutamate amounts also increased. In contrast, the possible precursor metabolites. 2-oxoglutarate (2-OG), malate and citrate, failed to stimulate GABA synthesis over the rate observed with control medium. Unlike malate and citrate. 2-OG reduced the decline in total glutamate observed when synaptosomes were incubated in control. In contrast to glutamine the production of synaptosomal glutamate from 2-OG, malate, and citrate is not great enough to stimulate GABA synthesis.
Battaglioli
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Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201-0509, USA.
Martin
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DL
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D005973:Glutamine / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013378:Substantia Nigra / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects*; D005680:gamma-Aminobutyric Acid / Q000096:biosynthesis*
D000596:Amino Acids; D005973:Glutamine; D005680:gamma-Aminobutyric Acid