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Presynaptic Modulation of Cholecystokinin Release by Protein Kinase C in the Rat Hippocampus
Author(s) -
Breukel Alexandra I. M.,
Wiegant Victor M.,
Lopes da Silva Fernando H.,
Ghijsen Wim E. J. M.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.70010341.x
Subject(s) - protein kinase c , chelerythrine , exocytosis , endocrinology , medicine , biology , synaptosome , agonist , chemistry , microbiology and biotechnology , receptor , biochemistry , signal transduction , secretion , central nervous system
The role of protein kinase C (PKC) in modulating the release of the octapeptide cholecystokinin (CCK‐8) was investigated in rat hippocampal nerve terminals (synaptosomes). The PKC‐activating phorbol ester 4β‐phorbol 12,13‐dibutyrate (β‐PDBu) dose dependently (5–5,000 n M ) increased CCK‐8 release in a strictly Ca 2+ ‐dependent way. This effect was observed only when synaptosomes were stimulated with the K + A channel blocker 4‐aminopyridine (4‐AP; 1 m M ) but not with KCI (10–30 m M ). The PDBu‐induced exocytosis of CCK‐8 was completely blocked by the two selective PKC inhibitors chelerythrine and calphostin‐C and was not mimicked by α‐PDBu, an inactive phorbol ester. In addition, an analogue of the endogenous PKC activator diacylglycerol, oleoylacetylglycerol, dose dependently increased CCK‐8 exocytosis. β‐PDBu (50–100 n M ) also stimulated the 4‐AP‐evoked Ca 2+ ‐dependent release of the classic transmitter GABA, which co‐localizes with CCK‐8 in hippocampal interneurons. As a possible physiological trigger for PKC activation, the role of the metabotropic glutamate receptor was investigated. However, the broad receptor agonist (1 S ,3 R )‐1‐aminocyclopentane‐1,3‐dicarboxylic acid did not stimulate, but instead inhibited, both the CCK‐8 and the GABA exocytosis. In conclusion, presynaptic PKC may stimulate exocytosis of distinct types of colocalizing neurotransmitters via modulation of presynaptic K + channels in rat hippocampus.