In vitro evidence that 5-hydroxytryptamine increases efflux of glial glutamate via 5-HT2A receptor activation
In vitro evidence that 5-hydroxytryptamine increases efflux of glial glutamate via 5-HT2A receptor activation
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DOI：
10.1002/jnr.10126
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发表时间：
2002-02-01
影响因子：
4.2
通讯作者：
Sharp, T
中科院分区：
文献类型：
--
作者：
Meller, R;Harrison, PJ;Sharp, T
最近的研究已确定培养物和大脑原位神经胶质细胞上存在 5-羟色胺 (5-HT)(2A) 受体。在这里，我们使用培养的 C6 神经胶质瘤细胞来研究神经胶质细胞上的 5-HT2A 受体调节细胞中谷氨酸释放的可能性。添加 5-HT 以浓度依赖性方式增加了培养的 C6 神经胶质瘤细胞内源性谷氨酸的流出（最大效果 +200%）。丝氨酸和天冬氨酸的流出没有改变。非选择性 5-HT 受体激动剂喹嗪和选择性 5-HT2 受体激动剂 4-碘-2,5-二甲氧基苯丙胺（DOI；均为 0.01-100 muM）均模仿 5-HT 的作用。 5-HT2A 受体拮抗剂酮舍林 (1 μM) 和螺哌隆 (1 μM) 抑制对 5-HT、喹嗪和 DOI 的谷氨酸反应，而 5-HT 的作用不受 5-HT2B/C 受体拮抗剂 SB200646 (1 μM) 的抑制。 5-HT 对谷氨酸的影响是特异性的，因为它在低钙培养基中会降低，但速尿 (5 mM) 不会阻止这种影响，速尿可防止细胞肿胀诱导的谷氨酸释放。最后，谷氨酸摄取抑制剂 2,4,反式吡咯烷二羧酸 (50 muM) 不会阻断 5-HT 诱导的谷氨酸外流，因此不太可能参与谷氨酸转运。总之，5-HT 在 5-HT2A 受体激活后刺激 C6 神经胶质瘤细胞中谷氨酸的流出，并涉及钙依赖性机制。 (C) 2002 Wiley-Liss, Inc.
Recent studies have established the presence of 5-hydroxytryptamine (5-HT)(2A) receptors on glial cells in culture and in the brain in situ. Here we used cultured C6 glioma cells to investigate the possibility that 5-HT2A receptors on glia regulate glutamate release from the cell. The efflux of endogenous glutamate from cultured C6 glioma cells was increased by addition of 5-HT in a concentration-dependent manner (maximal effect +200%). The efflux of serine and aspartate was not altered. The effect of 5-HT was mimicked by both the nonselective 5-HT receptor agonist quipazine and the selective 5-HT2 receptor agonist 4-iodo-2,5-dimethoxyamphetamine (DOI; both 0.01-100 muM). The 5-HT2A receptor antagonists ketanserin (1 muM) and spiperone (1 muM) inhibited the glutamate response to 5-HT, quipazine, and DOI, whereas the effect of 5-HT was not inhibited by the 5-HT2B/C receptor antagonist SB200646 (1 muM). The effect of 5-HT on glutamate was specific in that it was reduced in low-calcium medium but was not prevented by furosemide (5 mM), which prevents cell swelling-induced glutamate release. Finally, the glutamate uptake inhibitor 2,4,trans-pyrollidine dicarboxylic acid (50 muM) did not block the 5-HT-induced efflux of glutamate, making involvement of glutamate transport unlikely. In conclusion, 5-HT stimulates the efflux of glutamate from C6 glioma cells following 5-HT2A receptor activation and involves a calcium-dependent mechanism. (C) 2002 Wiley-Liss, Inc.