Endogenous gamma-L-glutamyl and beta-L-aspartyl peptides and excitatory aminoacidergic neurotransmission in the brain.
The effects of gamma-L-glutamyl- and beta-L-aspartyl di- and tripeptides on glutamatergic neurotransmission were tested in vitro. Of the peptides, gamma-L-glutamylglutamate was the most effective inhibitor, comparable to glutamate, of both Na(+)-independent and Cl-/Ca(2+)-activated binding/transport of glutamate. gamma-L-glutamylglutamate was most effective in the midbrain and hypothalamus and gamma-L-glutamylaspartate in the hippocampus when tested on the Na(+)-independent binding. The Cl-/Ca(2+)-dependent binding/transport of glutamate was affected by gamma-glutamylaspartate most strongly in the hippocampus. gamma-L-glutamylglycine and beta-L-aspartylglycine moderately inhibited the Na(+)-dependent uptake of L-glutamate and D-aspartate while the other peptides were only weak inhibitors. Reduced and oxidized glutathione enhanced the uptake of L-glutamate. The K(+)-stimulated release of L-glutamate was enhanced by gamma-L-glutamylglutamate and -aspartate and the release of D-aspartate also by gamma-L-glutamylglycine. The results indicate that both pre- and postsynaptic events in glutamatergic neurotransmission are modulated by these endogenous acidic oligopeptides.
Department of Biomedical Sciences, University of Tampere, Finland.
V
V
Varga
R
R
Janáky
P
P
Saransaari
S S
SS
Oja
D000818:Animals; D001224:Aspartic Acid / Q000378:metabolism / Q000502:physiology; D001921:Brain / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D018846:Excitatory Amino Acids / Q000502:physiology*; D018698:Glutamic Acid / Q000378:metabolism / Q000502:physiology; D066298:In Vitro Techniques; D018377:Neurotransmitter Agents / Q000502:physiology*; D009842:Oligopeptides / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission / Q000502:physiology*; D013574:Synaptosomes / Q000378:metabolism
D018846:Excitatory Amino Acids; D018377:Neurotransmitter Agents; D009842:Oligopeptides; D001224:Aspartic Acid; D018698:Glutamic Acid