Department of Anesthesiology, Far-Eastern Memorial Hospital, New Taipei City, 220 Taiwan.
Prog Neuropsychopharmacol Biol Psychiatry. 2011 Aug 15;35(7):1785-93. doi: 10.1016/j.pnpbp.2011.06.012. Epub 2011 Jun 30.
There is abundant evidence suggesting the relevance of glutamate to depression and antidepressant mechanisms. Curcumin, a major active compound of Curcuma longa, has been reported to have the biological function of antidepressant. The aim of the present study was to investigate the effect of curcumin on endogenous glutamate release in nerve terminals of rat prefrontal cortex and the underlying mechanisms. The results showed that curcumin inhibited the release of glutamate that was evoked by exposing synaptosomes to the K(+) channel blocker 4-aminopyridine (4-AP). This phenomenon was blocked by the chelating the extracellular Ca(2+) ions, and by the vesicular transporter inhibitor bafilomycin A1, but was insensitive to the glutamate transporter inhibitor DL-threo-β-benzyl-oxyaspartate (DL-TBOA). Further experiments demonstrated that curcumin decreased depolarization-induced increase in Ca(2+), whereas it did not alter the resting membrane potential or 4-AP-mediated depolarization. Furthermore, the inhibitory effect of curcumin on evoked glutamate release was prevented by blocking the Ca(v)2.2 (N-type) and Ca(v)2.1 (P/Q-type) channels, but not by blocking intracellular Ca(2+) release or Na(+)/Ca(2+) exchange. These results suggest that curcumin inhibits evoked glutamate release from rat prefrontocortical synaptosomes by the suppression of presynaptic Ca(v)2.2 and Ca(v)2.1 channels. Additionally, we also found that the inhibitory effect of curcumin on 4-AP-evoked glutamate release was completely abolished by the clinically effective antidepressant fluoxetine. This suggests that curcumin and fluoxetine use a common intracellular mechanism to inhibit glutamate release from rat prefrontal cortex nerve terminals.
有大量证据表明谷氨酸与抑郁症和抗抑郁机制有关。姜黄素是姜黄的主要活性化合物，据报道具有抗抑郁的生物学功能。本研究旨在探讨姜黄素对大鼠前额皮质神经末梢内源性谷氨酸释放的影响及其机制。结果表明，姜黄素抑制了 4-氨基吡啶（4-AP）阻断 K+通道时诱发的谷氨酸释放。这种现象被螯合细胞外 Ca2+所阻断，也被囊泡转运抑制剂巴佛洛霉素 A1 所阻断，但对谷氨酸转运抑制剂 DL-threo-β-苄基-氧基天冬氨酸（DL-TBOA）不敏感。进一步的实验表明，姜黄素降低了去极化诱导的[Ca2+]（C）增加，但不改变静息膜电位或 4-AP 介导的去极化。此外，姜黄素对诱发谷氨酸释放的抑制作用被阻断 Ca(v)2.2（N 型）和 Ca(v)2.1（P/Q 型）通道所阻止，但不被阻断细胞内 Ca2+释放或 Na+/Ca2+交换所阻止。这些结果表明，姜黄素通过抑制突触前 Ca(v)2.2 和 Ca(v)2.1 通道来抑制大鼠前额皮质突触小体中诱发的谷氨酸释放。此外，我们还发现，临床有效的抗抑郁药氟西汀完全消除了姜黄素对 4-AP 诱发的谷氨酸释放的抑制作用。这表明姜黄素和氟西汀使用共同的细胞内机制来抑制大鼠前额皮质神经末梢的谷氨酸释放。
