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 tripeptid es on glutamatergic neurotransmission were tested in vitro. Of the pep tides, gamma-L-glutamylglutamate was the most effective inhibitor, com parable to glutamate, of both Na+-independent and Cl-/Ca2+-activated b inding/transport of glutamate. gamma-L-glutamylglutamate was most effe ctive in the midbrain and hypothalamus and gamma-L-glutamylglutamate i n the hippocampus when tested on the Na+-independent binding. The Cl-/ Ca2+-dependent binding/transport of glutamate was affected by gamma-gl utamylaspartate most strongly in the hippocampus. gamma-L-glutamylglyc ine and beta-L-aspartylglycine moderately inhibited the Na+-dependent uptake of L-glutamate and D-aspartate while the other peptides were on ly weak inhibitors. Reduced and oxidized glutathione enhanced the upta ke of L-glutamate. The K+-stimulated release of L-glutamate was enhanc ed by gamma-L-glutamylglutamate and -aspartate and the release of D-as partate also by gamma-L-glutamylglycine. The results indicate that bot h pre- and postsynaptic events in glutamatergic neurotransmission are modulated by these endogenous acidic oligopeptides.