Theanine, an ingredient of green tea, inhibits [3H]glutamine transport in neurons and astroglia in rat brain

Theanine, an ingredient of green tea, inhibits [3H]glutamine transport in neurons and astroglia in rat brain
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DOI:
10.1002/jnr.21637
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发表时间:
2008-06-01
影响因子:
4.2
通讯作者:
Yoneda, Yukio
Yoneda, Yukio
中科院分区:
医学3区
文献类型:
--
作者:
Kakuda, Takami;Hinoi, Eiichi;Yoneda, Yukio

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我们之前已经证明,茶氨酸(=γ-谷氨酰-乙基酰胺)是绿茶的一种成分,对沙鼠大脑海马 CA1 区的缺血性神经元死亡具有保护作用,而不影响配体与结构上与茶氨酸相关的神经递质谷氨酸离子型受体亚型的结合。谷氨酸神经递质库被认为是由另一种结构类似物谷氨酰胺 (Gin) 的进入以及随后谷氨酰胺酶的裂解来促进的。尽管茶氨酸不抑制[H-3]谷氨酸积累,但[H-3]茶氨酸在大鼠脑突触体部分中以温度依赖性和饱和方式积极积累。 Gin 以浓度依赖性方式显着抑制[H-3]茶氨酸的积累,而茶氨酸则抑制[H-3]Gln 的积累,反之亦然。用氯化胆碱替代氯化钠后,[3 H]茶氨酸和[H-3]Gln 积累量均减少,端脑结构中的分布情况也类似。在培养的大鼠新皮质星形胶质细胞和神经元中,30℃下30分钟内观察到[H-3]茶氨酸和[H-3]Gln的积累达到类似的平衡,而茶氨酸在0.1-10 mM时以浓度依赖性方式抑制[H-3]Gln积累。此外,持续暴露于 10 mM 茶氨酸会导致培养神经元释放的细胞外谷氨酸水平显着下降。这些结果表明,绿茶成分茶氨酸可能是不同转运蛋白的抑制剂,这些转运蛋白能够跨质膜转运杜松子酒,以调节神经元中谷氨酸神经递质库所需的谷氨酸/谷氨酰胺循环。 (c) 2008 年 Wiley-Liss, Inc.
We have previously shown that theanine (=gamma-glutamyl-ethylamide), an ingredient of green tea, has a protective effect against ischemic neuronal death in the hippocampal CA1 region of the gerbil brain without affecting ligand binding to ionotropic receptor subtypes of the neurotransmitter glutamate structurally related to theanine. The neurotransmitter pool of glutamate is thought to be fueled by the entry of the other structural analog glutamine (Gin) and subsequent cleavage by glutaminase. Although theanine did not inhibit [H-3]glutamate accumulation, [H-3]theanine was actively accumulated in a temperature-dependent and saturable manner in rat brain synaptosomal fractions. The accumulation of [H-3]theanine was markedly inhibited by Gin in a concentration-dependent manner, whereas [H-3]Gln accumulation was inhibited by theanine vice versa. Both [3 H]theanine and [H-3]Gln accumulations were decreased after the replacement of sodium chloride with choline chloride, along with similarly high distribution profiles in telencephalic structures. A similar equilibrium was observed within 30 min at 30 degrees C for the accumulations of both [H-3]theanine and [H-3]Gln in cultured rat neocortical astroglia as well as neurons, whereas theanine inhibited [H-3]Gln accumulation in a concentration-dependent manner at 0.1-10 mM. Furthermore, sustained exposure to 10 mM theanine led to a significant decrease in the level of extracellular glutamate released from cultured neurons. These results suggest that the green tea ingredient theanine would be an inhibitor of different transporters capable of transporting Gin across plasma membranes toward the modulation of the glutamate/Gln cycle required for the neurotransmitter pool of glutamate in neurons. (c) 2008 Wiley-Liss, Inc.