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 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.
Breukel
A I
AI
Graduate School Neurosciences, Institute for Neurobiology, University of Amsterdam, The Netherlands.
Lopes da Silva
F H
FH
Ghijsen
W E
WE
D000818:Animals; D018846:Excitatory Amino Acids / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects; D018682:GABA Agents / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D009411:Nerve Endings / Q000187:drug effects* / Q000378:metabolism; D009557:Nipecotic Acids / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011949:Receptors, Cholecystokinin / Q000187:drug effects; D012844:Sincalide / Q000494:pharmacology*; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism
D018846:Excitatory Amino Acids; D018682:GABA Agents; D009557:Nipecotic Acids; D011949:Receptors, Cholecystokinin; C045598:N-(4,4-diphenyl-3-butenyl)nipecotic acid; D012844:Sincalide