Luteolin Inhibits the Release of Glutamate in Rat Cerebrocortical Nerve Terminals
2011
Lin, Tzu-Yu | Lu, Cheng Wei | Chang, Chia Chien | Huang, Shu Kuei | Wang, Su Jane
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 Ca2+ ions and by the vesicular transporter inhibitor, but was insensitive to the glutamate transporter inhibitor. Luteolin decreased the 4-AP-induced increase in [Ca2+]C, whereas it did not alter 4-AP-mediated depolarization. Furthermore, the effect of luteolin on evoked glutamate release was abolished by blocking the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, but not by blocking the ryanodine receptors or the mitochondrial Na+/Ca2+ 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 Ca2+ entry and MEK/ERK signaling cascade.
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