Modulation of glutamate agonist-induced influx of calcium into neurons by gamma-L-glutamyl and beta-L-aspartyl dipeptides.
Gamma-L-Glutamate and beta-L-aspartate dipeptides, present in the mammalian brain with a yet unknown function, were shown to affect the influx of Ca2+ into cultured cerebellar granule cells. The most active peptides, gamma-L-glutamyl-L-aspartate, gamma-L-glutamyl-L-glutamate and gamma-L-glutamylglycine, enhanced the basal influx but inhibited the glutamate-activated influx of Ca2+ in a dose-dependent manner. Gamma-L-Glutamyl-L-aspartate, the strongest inhibitor of the glutamate-activated influx of Ca2+, exhibited selective Mg(2+)-dependent antagonism in the N-methyl-D-aspartate (NMDA)-activated influx of Ca2+. This finding may explain its previously shown deleterious effects on the long-term memory. On the other hand, gamma-L-glutamyl-L-aspartate enhanced alone the entry of Ca2+ into neurons. This effect was antagonized by the non-NMDA antagonists 6-nitro-7-cyanoquinoxaline-2,3-dione (CNQX) and 6,7-dinitroquinoxaline-2,3-dione (DNQX), suggesting a non-NMDA receptor-mediated action, that may also be involved in excitotoxicity in some neurodegenerative disorders.
Tampere Brain Research Center, Department of Biomedical Sciences, University of Tampere, Finland.
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Janáky
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Oja
D000818:Animals; D001224:Aspartic Acid / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D004151:Dipeptides / Q000494:pharmacology; D005971:Glutamates / Q000494:pharmacology* / Q000502:physiology*; D018698:Glutamic Acid; D009474:Neurons / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology
D004151:Dipeptides; D005971:Glutamates; D009479:Neuropeptides; D001224:Aspartic Acid; D018698:Glutamic Acid; D002118:Calcium