Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City, Taiwan; Department of Mechanical Engineering, Yuan Ze University, Taoyuan, Taiwan.
Neurotoxicology. 2013 Dec;39:1-9. doi: 10.1016/j.neuro.2013.07.009. Epub 2013 Aug 7.
Quercetin, a naturally occurring flavonoid, has been reported to have a neuroprotective profile. An excessive release of glutamate is widely considered to be one of the molecular mechanisms of neuronal damage in several neurological diseases. This study investigated whether quercetin affected glutamate release in rat cerebral cortex nerve terminals (synaptosomes) and explored the possible mechanism. Quercetin inhibited the release of glutamate evoked by the K(+) channel blocker 4-aminopyridine (4-AP), and this effect was prevented by the chelating extracellular Ca(2+) ions. Quercetin decreased the depolarization-induced increase in the cytosolic free Ca(2+) concentration ([Ca(2+)]C), whereas it did not alter 4-AP-mediated depolarization and Na(+) influx. The quercetin-mediated inhibition of glutamate release was prevented by blocking the Cav2.2 (N-type) and Cav2.1 (P/Q-type) channels, but not by blocking intracellular Ca(2+) release. Combined inhibition of protein kinase C (PKC) and protein kinase A (PKA) also prevented the inhibitory effect of quercetin on evoked glutamate release. Furthermore, quercetin decreased the 4-AP-induced phosphorylation of PKC and PKA. These results suggest that quercetin inhibits glutamate release from rat cortical synaptosomes and this effect is linked to a decrease in presynaptic voltage-dependent Ca(2+) entry and to the suppression of PKC and PKA activity.
槲皮素是一种天然存在的类黄酮，已被报道具有神经保护作用。谷氨酸的过度释放被广泛认为是几种神经疾病中神经元损伤的分子机制之一。本研究探讨了槲皮素是否影响大鼠大脑皮质神经末梢（突触体）中的谷氨酸释放，并探讨了可能的机制。槲皮素抑制了 K(+)通道阻断剂 4-氨基吡啶（4-AP）引起的谷氨酸释放，而这种作用被螯合细胞外 Ca(2+)离子所阻止。槲皮素降低了去极化诱导的细胞浆游离 Ca(2+)浓度 ([Ca(2+)]C)的增加，但不改变 4-AP 介导的去极化和 Na(+)内流。Cav2.2（N 型）和 Cav2.1（P/Q 型）通道阻断可阻止槲皮素介导的谷氨酸释放抑制，但不改变 Cav2.2（N 型）和 Cav2.1（P/Q 型）通道介导的去极化和 Na(+)内流。同时抑制蛋白激酶 C（PKC）和蛋白激酶 A（PKA）也阻止了槲皮素对诱发谷氨酸释放的抑制作用。此外，槲皮素降低了 4-AP 诱导的 PKC 和 PKA 的磷酸化。这些结果表明，槲皮素抑制大鼠皮质突触体中谷氨酸的释放，这种作用与减少突触前电压依赖性 Ca(2+)内流以及抑制 PKC 和 PKA 活性有关。
