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Int. J. Mol. Sci. 2012, 13(7), 9097-9109; doi:10.3390/ijms13079097
Article

Curcumin Inhibits Glutamate Release from Rat Prefrontal Nerve Endings by Affecting Vesicle Mobilization

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Received: 20 June 2012 / Revised: 11 July 2012 / Accepted: 16 July 2012 / Published: 20 July 2012
(This article belongs to the Special Issue Plant-Derived Pharmaceuticals by Molecular Farming 2012)
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Abstract

Curcumin, one of the major constituents of Curcuma longa, has been shown to inhibit depolarization-evoked glutamate release from rat prefrontocortical nerve terminals by reducing voltage-dependent Ca2+ entry. This study showed that curcumin inhibited ionomycin-induced glutamate release and KCl-evoked FM1-43 release, suggesting that some steps after Ca2+ entry are regulated by curcumin. Furthermore, disrupting the cytoskeleton organization using cytochalasin D abolished the inhibitory action of curcumin on ionomycin-induced glutamate release. Mitogen-activated protein kinase kinase (MEK) inhibition also prevented the inhibitory effect of curcumin on ionomycin-induced glutamate release. Western blot analyses showed that curcumin decreased the ionomycin-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synaptic vesicle-associated protein synapsin I, the main presynaptic target of ERK. These results show that curcumin-mediated inhibition of glutamate release involves modulating downstream events by controlling synaptic vesicle recruitment and exocytosis, possibly through a decrease of MAPK/ERK activation and synapsin I phosphorylation, thereby decreasing synaptic vesicle availability for exocytosis.
Keywords: curcumin; glutamate exocytotic machinery; ERK; synapsin I; prefrontocortical nerve terminals curcumin; glutamate exocytotic machinery; ERK; synapsin I; prefrontocortical nerve terminals
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Lin, T.Y.; Lu, C.W.; Huang, S.K.; Wang, S.J. Curcumin Inhibits Glutamate Release from Rat Prefrontal Nerve Endings by Affecting Vesicle Mobilization. Int. J. Mol. Sci. 2012, 13, 9097-9109.

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