Glutamate transporter-mediated glutamate secretion in the mammalian pineal gland.
Glutamate transporter-mediated glutamate secretion in the mammalian pineal gland.
复制标题
哺乳动物松果体中的谷氨酸转运蛋白介导的谷氨酸分泌。
DOI：
10.1523/jneurosci.0894-08.2008
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发表时间：
2008-10-22
期刊：
影响因子：
--
通讯作者：
Koh DS
中科院分区：
文献类型：
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作者：
Kim MH;Uehara S;Muroyama A;Hille B;Moriyama Y;Koh DS
谷氨酸转运蛋白在整个中枢神经系统中表达，其主要作用是清除突触前末梢释放的谷氨酸。在这里，我们报告了大鼠松果体细胞中转运蛋白的新功能。这种生电转运蛋白响应 L-谷氨酸和 L-或 D-天冬氨酸而传导内向电流，并在膜片钳实验中使膜去极化。 Ca2+ 成像表明，转运蛋白介导的去极化通过电压门控 Ca2+ 通道诱导大量 Ca2+ 流入。通过碳纤维电流分析法和高效液相色谱法检测到，Ca2+ 的升高最终引发了谷氨酸胞吐作用。在含有密集松果体细胞的松果体切片中，从细胞中释放的谷氨酸有效地激活了邻近细胞中的谷氨酸转运蛋白。 KCl 去极化或乙酰胆碱产生的 Ca2+ 信号通过再生“谷氨酸诱导的谷氨酸释放”在多个细胞层中传播。因此，我们认为谷氨酸转运蛋白介导 L-谷氨酸的同步升高，从而通过先前在松果体中识别的抑制性代谢型谷氨酸受体有效地下调褪黑激素的分泌。
Glutamate transporters are expressed throughout the central nervous system where their major role is to clear released glutamate from presynaptic terminals. Here we report a novel function of the transporter in rat pinealocytes. This electrogenic transporter conducted inward current in response to L-glutamate and L- or D-aspartate and depolarized the membrane in patch clamp experiments. Ca2+ imaging demonstrated that the transporter-mediated depolarization induced a significant Ca2+ influx through voltage-gated Ca2+ channels. The Ca2+ rise finally evoked glutamate exocytosis as detected by carbon-fiber amperometry and by high-performance liquid chromatography. In pineal slices with densely packed pinealocytes, glutamate released from the cells effectively activated glutamate transporters in neighboring cells. The Ca2+ signal generated by KCl depolarization or acetylcholine propagated through several cell layers by virtue of the regenerative ‘glutamate-induced glutamate release’. Therefore we suggest that glutamate transporters mediate synchronized elevation of L-glutamate and thereby efficiently down-regulate melatonin secretion via previously identified inhibitory metabotropic glutamate receptors in the pineal gland.