The glycine transport inhibitor sarcosine is an inhibitory glycine receptor agonist.
The glycine transport inhibitor sarcosine is an inhibitory glycine receptor agonist.
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甘氨酸转运抑制剂肌氨酸是一种抑制性甘氨酸受体激动剂。
DOI：
10.1016/j.neuropharm.2009.07.019
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发表时间：
2009
影响因子：
4.7
通讯作者：
Thio,LiuLin
中科院分区：
文献类型：
--
作者：
Zhang,HaiXia;Lyons-Warren,Ariel;Thio,LiuLin
肌氨酸是一种内源性氨基酸，是I型甘氨酸转运蛋白（GlyT 1）的竞争性抑制剂、N-甲基-d-天冬氨酸受体（NMDAR）共激动剂和一碳代谢的重要中间体。其对精神分裂症的治疗潜力进一步强调了其临床重要性。肌氨酸和甘氨酸之间的结构相似性以及肌氨酸作为NMDAR共激动剂的能力使我们检查肌氨酸是否也是抑制性甘氨酸受体（GlyR）的激动剂。我们使用培养的胚胎小鼠海马神经元的全细胞记录研究了这种可能性，发现肌氨酸诱发了剂量依赖性的、士的宁敏感的Cl−电流，该电流交叉抑制甘氨酸电流。肌氨酸在细胞外溶液中用Li+阻断GlyT 1，在用基本上不可逆的GlyT 1抑制剂N[3-（4 ′-氟苯基）-3-（4′-苯基苯氧基）丙基]肌氨酸（NFPS）处理的神经元中，以及在没有胶质细胞的情况下接种的神经元中诱发这种电流。这些结果表明肌氨酸电流不是由GlyT 1抑制或异交换引起的。我们得出结论，肌氨酸是一种GlyR激动剂。
Sarcosine is an endogenous amino acid that is a competitive inhibitor of the type I glycine transporter (GlyT1), an N-methyl-d-aspartate receptor (NMDAR) co-agonist, and an important intermediate in one-carbon metabolism. Its therapeutic potential for schizophrenia further underscores its clinical importance. The structural similarity between sarcosine and glycine and sarcosine's ability to serve as an NMDAR co-agonist led us to examine whether sarcosine is also an agonist at the inhibitory glycine receptor (GlyR). We examined this possibility using whole-cell recordings from cultured embryonic mouse hippocampal neurons and found that sarcosine evoked a dose-dependent, strychnine sensitive, Cl−current that cross-inhibited glycine currents. Sarcosine evoked this current with Li+in the extracellular solution to block GlyT1, in neurons treated with the essentially irreversible GlyT1 inhibitor N[3-(4′-fluorophenyl)-3-(4′-phenylphenoxy)propyl]sarcosine (NFPS), and in neurons plated in the absence of glia. These results indicate that the sarcosine currents did not result from GlyT1 inhibition or heteroexchange. We conclude that sarcosine is a GlyR agonist.