Presynaptic Modulation of Cholecystokinin Release by Protein Kinase C in the Rat Hippocampus |
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Authors: | Alexandra I. M. Breukel Victor M. Wiegant Fernando H. Lopes da Silva Wim E. J. M. Ghijsen |
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Affiliation: | Institute for Neurobiology, Graduate School of Neurosciences, University of Amsterdam, Amsterdam;and; Department of Medical Pharmacology, Rudolf Magnus Institute for Neuroscience, Utrecht University, Utrecht, The Netherlands |
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Abstract: | Abstract: 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 Ca2+-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 Ca2+-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. |
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Keywords: | Cholecystokinin γ-Aminobutyric acid Exocytosis Protein kinase C Hippocampus Synaptosomes |
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