Amino Acid Neurotransmitters; Mechanisms of Their Uptake into Synaptic Vesicles

摘要

In the present work it was shown that GABA and L-glutamate (later termedglutamate) were taken up by a Mg(2+) and ATP dependent mechanism into synaptic vesicles isolated from rat brain. The vesicular uptake differed clearly from the synaptosomal and glial cell uptake, both with respect to Na(+), Mg(2+) and ATP dependency. The uptake of glutamate and GABA was inhibited by similar, but not identical concentrations of different ionophores and by inhibitors of the Mg(2+)-ATPase. The uptake of glutamate was dependent on the presence of low concentrations of Cl(-) or Br(-) in the incubation medium, whereas the uptake of GABA was not. In addition the uptake of glutamate was more potently inhibited by blockers of Cl(-) exchange than the uptake of GABA. The results indicate involvement of the Cl(-) exchanger in the uptake of glutamate. The regional distribution in the brain of the uptake of GABA and glutamate was found to be different. The substrate specificity of the uptake of GABA and glycine was similar, and the vesicular uptake of GABA and glycine was competitively inhibited by different structure analogues. These results support the concept that synaptic vesicles are important for storage of amino acids in the nerve terminal. The mechanisms of the uptake of glutamate and GABA are different, whereas the mechanisms of the uptake of GABA and glycine seem to be similar.