title: Effects of sarcosine and N, N-dimethylglycine on NMDA receptor-mediated excitatory field potentials.
abstract: 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.
authors.affiliation: Master/PhD Program in Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 97004, Taiwan.
authors.forename: Mei-Yi
authors.initials: MY
authors.lastname: Lee
authors.affiliation: Master/PhD Program in Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 97004, Taiwan.
authors.forename: Yi-Ruu
authors.initials: YR
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, 1, Sec. 4, Roosevelt Rd., Taipei, 10617, Taiwan.
authors.forename: Yi-Shu
authors.initials: YS
authors.lastname: Tu
authors.affiliation: Institute of Biomedical Electronics and Bioinformatics, National Taiwan University, 1, Sec. 4, Roosevelt Rd., Taipei, 10617, Taiwan.|Department of Computer Science and Information Engineering, National Taiwan University, 1, Sec. 4, Roosevelt Rd., Taipei, 10617, Taiwan.
authors.forename: Yufeng Jane
authors.initials: YJ
authors.lastname: Tseng
authors.affiliation: Institute of Neuroscience, National Chengchi University, 64, Sec. 2, ZhiNan Road, Wenshan District, Taipei City, 11605, Taiwan. minghuan@nccu.edu.tw.|Research Center for Mind, Brain, and Learning, National Chengchi University, 64, Sec. 2, ZhiNan Road, Wenshan District, Taipei City, 11605, Taiwan. minghuan@nccu.edu.tw.
authors.forename: Ming-Huan
authors.initials: MH
authors.lastname: Chan
authors.affiliation: Master/PhD Program in Pharmacology and Toxicology, Tzu Chi University, 701, Section 3, Chung-Yang Road, Hualien, 97004, Taiwan. hwei@nhri.org.tw.|Institute of Neuroscience, National Chengchi University, 64, Sec. 2, ZhiNan Road, Wenshan District, Taipei City, 11605, Taiwan. hwei@nhri.org.tw.|Center for Neuropsychiatric Research, National Health Research Institutes, 35 Keyan Road, Zhunan, Miaoli County, 35053, Taiwan. hwei@nhri.org.tw.
authors.forename: Hwei-Hsien
authors.initials: HH
authors.lastname: Chen
mesh_terms: D000818:Animals; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D008813:Mice, Inbred ICR; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000378:metabolism*; D012521:Sarcosine / Q000031:analogs & derivatives* / Q000494:pharmacology*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; C025138:dimethylglycine; D012521:Sarcosine
keywords: 7-chlorokynurenate; D-cycloserine; D-serine; Glycine binding site; N-methylglycine