AGING IS ASSOCIATED WITH CHANGES IN GLUTAMATE RELEASE, PROTEIN-TYROSINE KINASE AND CA2+ CALMODULIN-DEPENDENT PROTEIN-KINASE-II IN RAT HIPPOCAMPUS/

We have used synaptosomes prepared from rat hippocampus to investigate the role of protein tyrosine kinase and Ca2+/calmodulin-dependent pro tein kinase II in modulating glutamate release in young animals and to investigate possible parallel age-related changes in release and kina se activity. We report that depolarization of synaptosomes with 40 mM KCl, which stimulated glutamate release, also significantly increased activity of both kinases, while the protein tyrosine kinase inhibitor, genistein and the Ca2+/calmodulin-dependent protein kinase II inhibit or, KN62 O-bis[5-isoquinolinesulfonyl]-N-methyl-tyrosyl)-4- phenylpipe razine) decreased K+-stimulated, Ca2+-dependent release of glutamate. K+-stimulated release of glutamate was significantly decreased in hipp ocampal synaptosomes prepared from aged, compared to young, animals. I n parallel with these changes in release, we report an age-related dec rease in activities of both protein tyrosine kinase and Ca2+/calmoduli n-dependent protein kinase II. We conclude that these kinases play a r ole in modulating release of glutamate in hippocampus and that the age -related decrease in glutamate release may be partly due to an age-rel ated decrease in kinase activities.