title: Luteolin inhibits the release of glutamate in rat cerebrocortical nerve terminals.
abstract: The present study investigated the effect and possible mechanism of luteolin, a food-derived flavonoid, on endogenous glutamate release in nerve terminals of rat cerebral cortex (synaptosomes). Luteolin inhibited the release of glutamate evoked by the K(+) channel blocker 4-aminopyridine (4-AP), and this phenomenon was concentration-dependent. The effect of luteolin on the evoked glutamate release was prevented by the chelation of the extracellular Ca(2+) ions and by the vesicular transporter inhibitor, but was insensitive to the glutamate transporter inhibitor. Luteolin decreased the 4-AP-induced increase in [Ca(2+)](C), whereas it did not alter 4-AP-mediated depolarization. Furthermore, the effect of luteolin on evoked glutamate release was abolished by blocking the Ca(v)2.2 (N-type) and Ca(v)2.1 (P/Q-type) channels, but not by blocking the ryanodine receptors or the mitochondrial Na(+)/Ca(2+) exchange. In addition, the inhibitory effect of luteolin on evoked glutamate release was prevented by the mitogen-activated/extracellular signal-regulated kinase (MEK) inhibitors. Western blot analyses showed that luteolin decreased the 4-AP-induced phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and synapsin I, the main presynaptic target of ERK. Thus, it was concluded that luteolin inhibits glutamate release from rat cortical synaptosomes through the suppression of presynaptic voltage-dependent Ca(2+) entry and MEK/ERK signaling cascade.
authors: Department of Anesthesiology, Far-Eastern Memorial Hospital, Pan-Chiao District, New Taipei City, Taiwan.
authors: Tzu Yu
authors: TY
authors: Lin
authors: Cheng Wei
authors: CW
authors: Lu
authors: Chia Chien
authors: CC
authors: Chang
authors: Shu Kuei
authors: SK
authors: Huang
authors: Su Jane
authors: SJ
authors: Wang
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D015536:Down-Regulation / Q000187:drug effects*; D018698:Glutamic Acid / Q000378:metabolism*; D047311:Luteolin / Q000494:pharmacology*; D008297:Male; D009411:Nerve Endings / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism
chemical_list: D018698:Glutamic Acid; D047311:Luteolin