Premium
Osthole or imperatorin‐mediated facilitation of glutamate release is associated with a synaptic vesicle mobilization in rat hippocampal glutamatergic nerve endings
Author(s) -
Lin TzuYu,
Lu ChengWei,
Huang WeiJan,
Wang SuJane
Publication year - 2010
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20738
Subject(s) - ionomycin , chemistry , glutamate receptor , exocytosis , synaptic vesicle , microbiology and biotechnology , synapsin i , imperatorin , synaptic vesicle recycling , neuroscience , pharmacology , biology , biochemistry , vesicle , receptor , high performance liquid chromatography , chromatography , membrane , secretion , intracellular
Osthole and imperatorin, two active compounds of Cnidium monnieri (L.) Cusson, have previously been shown to facilitate depolarization‐evoked glutamate release from rat hippocampal nerve terminals by increasing voltage‐dependent Ca 2+ entry. In this study, we further investigated whether osthole and imperatorin possess an action at the exocytotic machinery itself, downstream of a Ca 2+ influx. Our data showed that ionomycin‐induced glutamate release and KCl‐evoked FM1‐43 release were facilitated by osthole and imperatorin, suggesting that some steps after Ca 2+ entry are regulated by these two compounds. Consistent with this, osthole or imperatorin‐mediated facilitation of ionomycin‐induced glutamate release was occluded by cytochalasin D that inhibits actin polymerization, implying that the disassembly of cytoskeleton is involved. In addition, the facilitatory action of osthole or imperatorin on ionomycin‐induced glutamate release was attenuated by the Ca 2+ /calmodulin‐dependent kinase II (CaMKII) inhibitor KN62. Furthermore, Western blotting analysis further showed that osthole or imperatorin significantly increased ionomycin‐induced phosphorylation of CaMKII and synapsin I, the main presynaptic target of CaMKII. These results suggest, therefore, that osthole or imperatorin‐mediated facilitation of glutamate release involves modulation of downstream events controlling synaptic vesicle recruitment and exocytosis, possibly through an increase of CaMKII activation and synapsin I phosphorylation, thereby increasing synaptic vesicle availability for exocytosis. Synapse 64:390–396, 2010. © 2009 Wiley‐Liss, Inc.