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 extracellular concentrations of glutamate results in excitotoxicity. Elevated levels of phosphomonoesters (PMEs), phosphodiesters (PDEs), and phosphocreatine (PCr) have been reported in Alzheimer disease (AD). In this article, the effects of selected PMEs, PDEs, and PCr on vesicular L-[3H]glutamate uptake into isolated bovine synaptic vesicles are investigated. D-myo-Inositol-1-monophosphate (I1P), D-myo-inositol-2-monophosphate (I2P), sn-glycero-3-phosphate, (alpha-GP) and PCr significantly stimulated L-[3H]glutamate uptake into synaptic vesicles. Phosphoethanolamine (PE), phosphocholine (PC), L-phosphoserine (L-PS) sn-glycero-3-phosphocholine (GPC), and sn-glycero-3-phosphoethanolamine (GPE) had little or no effect on vesicular L-glutamate uptake. These observations suggested that the vesicular uptake of glutamate can be regulated by endogenous PMEs and PCr. The mechanism of activation by I1P, I2P, and alpha-GP appears to be stimulation of Mg(2+)-ATPase activity. These effects on vesicular glutamate uptake may be important in diseases in which the levels of these metabolites are altered, as they are in AD.
Xu
C J
CJ
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh Medical Center, PA 15261, USA.
Kanfer
J N
JN
Klunk
W E
WE
Xiong
Q
Q
McClure
R J
RJ
Pettegrew
J W
JW
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D017301:Ca(2+) Mg(2+)-ATPase / Q000378:metabolism; D002417:Cattle; D018698:Glutamic Acid / Q000378:metabolism*; D005994:Glycerophosphates / Q000378:metabolism; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D007700:Kinetics; D010710:Phosphates / Q000494:pharmacology*; D010725:Phosphocreatine / Q000494:pharmacology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*
D000596:Amino Acids; D005994:Glycerophosphates; D010710:Phosphates; D010725:Phosphocreatine; D018698:Glutamic Acid; D007294:Inositol; D017301:Ca(2+) Mg(2+)-ATPase