Stimulatory effect of arachidonic acid on the release of GABA in matrix-enriched areas from the rat striatum

Arachidonic acid was shown to stimulate the release of preloaded [H-3]GABA from microdiscs of tissue punched out in matrix-enriched areas of the rat striatum. This effect, which was calcium- and dose-dependent, persisted in the presence of inhibitors of arachidonic acid catabolism. Other fatty acids were less or not effective. Arachidonic acid also inhibited [H-3]GABA uptake into purified striatal synaptosomes, however the arachidonic acid-evoked release of [H-3]GABA persisted following inhibition of the GABA neuronal uptake process. The stimulatory effect of arachidonic acid on GABA release may largely result from the activation of a protein kinase C since the arachidonic acid response was reduced by several protein kinase C inhibitors. Arachidonic acid also dose-dependently stimulated the release of preloaded [H-3]GABA from purified striatal synaptosomes. Similar results were obtained when synaptosomes were previously incubated with [H-3]glutamine to study the release of endogenously synthesized [H-3]GABA. Further indicating a direct action of the fatty acid on GABAergic neurons, the arachidonic acid-induced release of [H-3]GABA from microdiscs was not modified in the presence of the D-1 dopaminergic antagonist SCH23390 or of glutamatergic antagonists. Finally, the release of [H-3]GABA evoked by the combined application of NMDA and carbachol (a treatment known to markedly stimulate arachidonic acid formation) was reduced by inhibitors of phospholipase A(2) further indicating that endogenously formed arachidonic acid significantly facilitates the release of GABA in the striatum.