Modulation of dopamine uptake and release in rat striatal synaptosomes by glycine and glutamate.

Abstract

The uptake and release of dopamine (DA) by rat brain striatal synaptosomes were studied in presence of glycine or glutamate (0.5-20 mM) in incubation media containing 5 or 55 mM KCl. In low K+ medium glycine, up to 5 mM had little effect on DA uptake, but higher concentrations of the amino acid inhibited the uptake. High K+ medium resulted in a decrease in DA uptake as compared to that of basal K+ medium. Glycine at 1 microM, but not at higher concentrations, prevented the inhibition induced by high K+ depolarization. However, glutamate in the low K+ medium and at a 0.5 mM concentration, stimulated DA uptake, but at higher concentrations it inhibited the uptake. In the high K+ medium, glutamate in all concentrations potentiated the inhibition of DA uptake induced by K+ depolarization. The DA release response of the synaptosomes to glycine concentrations (1-20 mM) in low K+ medium was a biphasic pattern, with a stimulation at 1 mM and an inhibition at higher concentrations. This pattern was reversed when DA release was measured in the high K+ medium. The pattern of DA release in the presence of glutamate concentrations (1-20 mM) was a triphasic one, with an inhibition at 1 mM, stimulation at 5 mM, and a less effective inhibition at higher concentrations. In the high K+ medium, glutamate at 1 mM concentration prevented the stimulation induced by K+ depolarization, but at 5 mM reversed the rate of release to the depolarization state. Results of this study suggest that glycine and glutamate have more than a simple inhibitory or excitatory transmitter role in the striatum, respectively. The identical effects of glycine with that of glutamate in certain concentrations is consistent with previous reports that glycine and N-methyl-D-aspartate (NMDA) act as coagonists of a common excitatory amino acid receptor.