title: Echinacoside Inhibits Glutamate Release by Suppressing Voltage-Dependent Ca(2+) Entry and Protein Kinase C in Rat Cerebrocortical Nerve Terminals.
abstract: The glutamatergic system may be involved in the effects of neuroprotectant therapies. Echinacoside, a phenylethanoid glycoside extracted from the medicinal Chinese herb Herba Cistanche, has neuroprotective effects. This study investigated the effects of echinacoside on 4-aminopyridine-evoked glutamate release in rat cerebrocortical nerve terminals (synaptosomes). Echinacoside inhibited Ca(2+)-dependent, but not Ca(2+)-independent, 4-aminopyridine-evoked glutamate release in a concentration-dependent manner. Echinacoside also reduced the 4-aminopyridine-evoked increase in cytoplasmic free Ca(2+) concentration but did not alter the synaptosomal membrane potential. The inhibitory effect of echinacoside on 4-aminopyridine-evoked glutamate release was prevented by ω-conotoxin MVIIC, a wide-spectrum blocker of Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, but was insensitive to the intracellular Ca(2+) release-inhibitors dantrolene and 7-chloro-5-(2-chloropheny)-1,5-dihydro-4,1-benzothiazepin-2(3H)-one (CGP37157). Furthermore, echinacoside decreased the 4-aminopyridine-induced phosphorylation of protein kinase C, and protein kinase C inhibitors abolished the effect of echinacoside on glutamate release. According to these results, we suggest that the inhibitory effect of echinacoside on evoked glutamate release is associated with reduced voltage-dependent Ca(2+) entry and subsequent suppression of protein kinase C activity.
authors.affiliation: Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan. drluchengwei@gmail.com.|Department of Mechanical Engineering, Yuan Ze University, Taoyuan 32003, Taiwan. drluchengwei@gmail.com.
authors.forename: Cheng Wei
authors.initials: CW
authors.lastname: Lu
authors.affiliation: Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City 22060, Taiwan. drlin1971@gmail.com.|Department of Mechanical Engineering, Yuan Ze University, Taoyuan 32003, Taiwan. drlin1971@gmail.com.
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. nskh9450n@yahoo.com.tw.
authors.forename: Shu Kuei
authors.initials: SK
authors.lastname: Huang
authors.affiliation: School of Medicine, Fu Jen Catholic University, No. 510, Zhongzheng Rd., Xinzhuang Dist., New Taipei 24205, Taiwan. med0003@mail.fju.edu.tw.
authors.forename: Su Jane
authors.initials: SJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology; D005089:Exocytosis; D018698:Glutamic Acid / Q000378:metabolism*; D006027:Glycosides / Q000494:pharmacology*; D008297:Male; D008564:Membrane Potentials; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D002121:Calcium Channel Blockers; D015220:Calcium Channels; D006027:Glycosides; D047428:Protein Kinase Inhibitors; D018698:Glutamic Acid; D011493:Protein Kinase C; C060297:echinacoside
keywords: cerebrocortical nerve terminals; echinacoside; glutamate release; protein kinase C; voltage-dependent Ca2+ channels