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 Ca2+, CCK-8S increased the basal release of glutamate, but not of aspartate and GABA. In addition, CCK-8S dose-dependently increased the KCl-evoked Ca2+-dependent release of both glutamate and aspartate to about 1.4-fold at concentrations > or = 0.5 microM. CCK-8S did not change the KCl-evoked Ca2+-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 (SK&F89976-A; 10 microM). The CCKB receptor antagonist L365,260 (1 microM) 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.