https://scholars.lib.ntu.edu.tw/handle/123456789/400621
標題: | Effects of sarcosine and N, N-dimethylglycine on NMDA receptor-mediated excitatory field potentials | 作者: | Mei-Yi Lee Yi-Ruu Lin Yi-Shu Tu Yufeng Jane Tseng Ming-Huan Chan Hwei-Hsien Chen YUFENG JANE TSENG |
關鍵字: | 7-chlorokynurenate; D-cycloserine; D-serine; Glycine binding site; N-methylglycine | 公開日期: | 二月-2017 | 卷: | 24 | 期: | 1 | 來源出版物: | Journal of Biomedical Science | 摘要: | Background: Sarcosine, a glycine transporter type 1 inhibitor and an N-methyl-D-aspartate (NMDA) receptor co-agonist at the glycine binding site, potentiates NMDA receptor function. Structurally similar to sarcosine, N,N-dimethylglycine (DMG) is also N-methyl glycine-derivative amino acid and commonly used as a dietary supplement. The present study compared the effects of sarcosine and DMG on NMDA receptor-mediated excitatory field potentials (EFPs) in mouse medial prefrontal cortex brain slices using a multi-electrode array system. Results: Glycine, sarcosine and DMG alone did not alter the NMDA receptor-mediated EFPs, but in combination with glutamate, glycine and its N-methyl derivatives significantly increased the frequency and amplitude of EFPs. The enhancing effects of glycine analogs in combination with glutamate on EFPs were remarkably reduced by the glycine binding site antagonist 7-chlorokynurenate (7-CK). However, DMG, but not sarcosine, reduced the frequency and amplitude of EFPs elicited by co-application of glutamate plus glycine. D-cycloserine, a partial agonist at the glycine binding site on NMDA receptors, affected EFPs in a similar manner to DMG. Furthermore, DMG, but not sarcosine, reduced the frequencies and amplitudes of EFPs elicited by glutamate plus D-serine, another endogenous ligand for glycine binding site. Conclusions: These findings suggest that sarcosine acts as a full agonist, yet DMG is a partial agonist at glycine binding site of NMDA receptors. The molecular docking analysis indicated that the interactions of glycine, sarcosine, and DMG to NMDA receptors are highly similar, supporting that the glycine binding site of NMDA receptors is a critical target site for sarcosine and DMG. ? 2017 The Author(s). |
URI: | http://scholars.lib.ntu.edu.tw/handle/123456789/400621 | DOI: | 10.1186/s12929-016-0314-8 | SDG/關鍵字: | 7 chlorokynurenic acid; dextro serine; dimethylglycine; n methyl dextro aspartic acid receptor; sarcosine; dimethylglycine; n methyl dextro aspartic acid receptor; sarcosine; animal experiment; animal tissue; Article; binding site; controlled study; electric potential; electrophysiology; enzyme activation; excitatory field potential; hydrogen bond; male; molecular docking; molecular interaction; mouse; nonhuman; protein expression; protein function; agonists; analogs and derivatives; animal; drug effects; Institute for Cancer Research mouse; membrane potential; metabolism; Animals; Male; Membrane Potentials; Mice; Mice, Inbred ICR; Receptors, N-Methyl-D-Aspartate; Sarcosine |
顯示於: | 生醫電子與資訊學研究所 |
在 IR 系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。