Glutamate as a Putative Transmitter in the Cerebellum: Stimulation by GABA of Glutamic Acid Release from Specific Pools

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Abstract
Whether the release of glutamate from putative glutamergic terminals in rat cerebellum is influenced by GABA was studied. A neurotransmitter role of glutamate evidently exists in the cerebellum because endogenous glutamate was released from depolarized cerebellar synaptosomal preparations in a Ca2+-dependent way [14C]glutamate was synthesized from [14C]glutamine in cerebellar synaptosomes and the newly synthesized [14C]glutamate was released in a Ca2+-dependent way and the elevation of cGMP elicited by depolarization of cerebellar slices in the presence of Ca2+ was partly reversed by the glutamate antagonist glutamic acid diethyl ester, which probably prevented the interaction of endogenously released glutamate with postsynaptic receptors. GABA and muscimol at low concentrations (2-20 .mu.M) potentiated the depolarization-induced release of D-[3H]aspartate (a glutamate analogue which labels the glutamate reuptake pool) from cerebellar synaptosomes. The effect was concentration dependent and was largely prevented by 2 GABA antagonists, bicuculline and picrotoxin. The stimulation of D-[3H]aspartate release evoked by muscimol was linearly related to the log of K+ concentration in the depolarizing medium. GABA did not affect the overall release of endogenous glutamate, but potentiated, in a picrotoxin-sensitive manner, the depolarization-evoked release of [14C]glutamate previously synthesized from [14C]glutamine. Since nerve endings are the major site of glutamate synthesis from glutamine, GABA and muscimol appear to exert their stimulatory effect at the level of glutamergic nerve terminals, probably after interacting with presynaptic GABA receptors. The possible functional significance of these findings is briefly discussed.