EXCITATORY AMINO ACID RECEPTORS ARE COUPLED WITH PHOSPHOINOSITIDE METABOLISM

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We have shown for the first time that specific dicarboxylic amino acid recognition sites are coupled with inositol phospholipid metabolism in the rat central nervous system. These sites are abundant in the hippocampus, sensitive to the stimulatory action of ibotenic acid and are selectively antagonized by 2-amino-4-phosphonobutyric acid (APB). Glutamic and aspartic acids have marginal effect on inositol phospholipid metabolism in slices from adult animals but they markedly enhance inositol phospholipid hydrolysis (up to 15 fold) in slices from newborn animals. This action of glutamic acid declines progressively from the day 6th to the day 19th after the birth up to reach the adult levels on the day 30th after the birth. In the adult, the stimulatory action of dicarboxylic amino acids on inosidol phospholipid hydrolysis is potentiated following repeated electrical stimulation of limbic structures or after toxin-induced lesions of hippocampal excitatory pathways. We suggest that the stimulation of inositol phospholipid hydrolysis elicited by dicarboxylic amino acid may have a role in the cellular mechanism(s) underlying neuronal development as well as the regulation of limbic excitability.