title: Curcumin inhibits glutamate release from rat prefrontal nerve endings by affecting vesicle mobilization.
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 Ca(2+) entry. This study showed that curcumin inhibited ionomycin-induced glutamate release and KCl-evoked FM1-43 release, suggesting that some steps after Ca(2+) 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.
authors.affiliation: Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan.|Department of Mechanical Engineering, Yuan Ze University, Taoyuan 320, Taiwan.
authors.forename: Tzu Yu
authors.initials: TY
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan.
authors.forename: Cheng Wei
authors.identifier: 0000-0002-2217-3231
authors.initials: CW
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan.
authors.forename: Shu Kuei
authors.initials: SK
authors.lastname: Huang
authors.affiliation: Graduate Institute of Basic Medicine, Jen Catholic University, No.510, Zhongzheng Rd., Xinzhuang District, New Taipei City 24205, Taiwan.|School of Medicine, Fu Jen Catholic University, No.510, Zhongzheng Rd., Xinzhuang District, New Taipei City 24205, Taiwan.
authors.forename: Su Jane
authors.identifier: 0000-0002-4675-0259
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D003474:Curcumin / Q000494:pharmacology*; D004789:Enzyme Activation; D005089:Exocytosis / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010525:Peripheral Nerves / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016704:Synapsins / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D016704:Synapsins; D048052:Mitogen-Activated Protein Kinase 3; D003474:Curcumin; D002118:Calcium