EFFECT OF PHOSPHOMONOESTERS, PHOSPHODIESTERS, AND PHOSPHOCREATINE ON GLUTAMATE UPTAKE BY SYNAPTIC VESICLES

L-Glutamate, a major excitatory amino acid, plays an important role in learning and memory. L-Glutamate uptake into synaptic vesicles is an ATP-dependent process. Exposure of neurons to high, sustained extracel lular concentrations of glutamate results in excito-toxicity. Elevated levels of phosphomonoesters (PMEs), phosphodiesters (PDEs), and phosp hocreatine (PCr) have been reported in Alzheimer disease (AD). In this article, the effects of selected PMEs, PDEs, and PCr on vesicular L-[ H-3]glutamate uptake into isolated bovine synaptic vesicles are invest igated. D-myo-Inositol-1-monophosphate (I1P), D-myo-inositol-2-monopho sphate (I2P), sn-glycero-3-phosphate, (alpha-GP) and PCr significantly stimulated L-[H-3]glutamate uptake into synaptic vesicles. Phosphoeth anolamine (PE), phosphocholine (PC), L-phosphoserine (L-PS) sn-glycero -3-phosphocholine (GPC), and sn-glycero-3-phosphoethanolamine (GPE) ha d little or no effect on vesicular L-glutamate uptake. These observati ons suggested that the vesicular uptake of glutamate can be regulated by endogenous PMEs and PCr. The mechanism of activation by I1P, I2P, a nd alpha-GP appears to be stimulation of Mg2+-ATPase activity. These e ffects on vesicular glutamate uptake may be important in di;eases in w hich the levels of these metabolites are altered, as they are in AD.