CHOLECYSTOKININ (CCK-8) MODULATES VESICULAR RELEASE OF EXCITATORY AMINO-ACIDS IN RAT HIPPOCAMPAL NERVE-ENDINGS

The modulation of endogenous amino acid transmitter release by the sul phated octapeptide cholecystokinin (CCK-8S) was investigated in purifi ed rat hippocampal synaptosomes. In the presence of extracellular Ca2, CCK-8S increased the basal release of glutamate, but not of aspartat e and GABA. In addition, CCK-8S dose-dependently increased the KCI-evo ked Ca2+-dependent release of both glutamate and aspartate to about 1. 4-fold at concentrations greater than or equal to 0.5 mu M. CCK-8S did not change the KCl-evoked Ca2+-dependent GABA release, not even in th e presence of the GABA uptake carrier blocker N-(4,4-diphenyl-3-buteny l)-3-piperidine carboxylic acid 89976-A (SK&F89976-A; 10 mu M). The CC KB receptor antagonist L365,260 (1 mu M) blocked the CCK-8S-induced re lease of glutamate by 70%, and of aspartate by 100%. In conclusion, CC K stimulates exocytosis of excitatory amino acids in rat hippocampus b y activating a low-affinity presynaptic CCK receptor, presumably of th e B-subtype. However, CCK does not modulate the release of GABA, which has been reported to be colocalized with this peptide. (C) 1997 Elsev ier Science Ireland Ltd.