Cholecystokinin (CCK-8) modulates vesicular release of excitatory amino acids in rat hippocampal nerve endings.

Abstract The modulation of endogenous amino acid transmitter release by the sulphated octapeptide cholecystokinin (CCK-8S) was investigated in purified rat hippocampal synaptosomes. In the presence of extracellular Ca 2+ , CCK-8S increased the basal release of glutamate, but not of aspartate and GABA. In addition, CCK-8S dose-dependently increased the KCl-evoked Ca 2+ -dependent release of both glutamate and aspartate to about 1.4-fold at concentrations ≥0.5 μ M. CCK-8S did not change the KCl-evoked Ca 2+ -dependent GABA release, not even in the presence of the GABA uptake carrier blocker N -(4,4-diphenyl-3-butenyl)-3-piperidine carboxylic acid 89976-A (SKF 10 μ M). The CCK B receptor antagonist L365,260 (1 μ M) blocked the CCK-8S-induced release of glutamate by 70%, and of aspartate by 100%. In conclusion, CCK stimulates exocytosis of excitatory amino acids in rat hippocampus by activating a low-affinity presynaptic CCK receptor, presumably of the B-subtype. However, CCK does not modulate the release of GABA, which has been reported to be colocalized with this peptide.