Summary
The activation of protein kinase C, (PKC), with phorbol esters in nerve terminals enhances the release of neurotransmitter glutamate. The presynaptic locus of PKC action is at the K+-channels controlling the duration or frequency of the action potentials; for this reason, the facilitation of glutamate release is observed only in synaptosomes under the repetitive depolarizations induced by the K+-channel blocker 4-aminopyridine, (4-AP), but not by the clamped depolarization induced by high KC1. The PKC isoform responsible for this increase in release is unknown but it is sensitive to both phorbol esters and cis-unsaturated fatty acids. A metabotropic receptor for glutamate generating diacylglycerol is involved in the activation of this PKC-dependent pathway. However, the potentiation of glutamate release is observed only in the presence of arachidonic acid. Arachidonic acid does not modify the generation of diacylglycerol induced by metabotropic agonists, but it is necessary for the phosphorylation of the major PKC-substrate in nerve terminals, the myristoylated-alanine-rich-C-Kinase substrate, (MARCKS), suggesting that the enhancement of release is based on the synergistic activation of PKC by diacylglycerol (DG) and arachidonic acid.
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Sánchez-Prieto, J., Vázquez, E., Herrero, I. (1994). Metabotropic Glutamate Receptors and the Activation of Protein Kinase C in the Control of Glutamate Release. In: Municio, A.M., Miras-Portugal, M.T. (eds) Cell Signal Transduction, Second Messengers, and Protein Phosphorylation in Health and Disease. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1879-2_6
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DOI: https://doi.org/10.1007/978-1-4615-1879-2_6
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