PMID- 25042179
OWN - NLM
STAT- MEDLINE
DCOM- 20150629
LR  - 20211021
IS  - 1755-5949 (Electronic)
IS  - 1755-5930 (Print)
IS  - 1755-5930 (Linking)
VI  - 20
IP  - 11
DP  - 2014 Nov
TI  - D-serine-induced inactivation of NMDA receptors in cultured rat hippocampal 
      neurons expressing NR2A subunits is Ca2+-dependent.
PG  - 951-60
LID - 10.1111/cns.12308 [doi]
AB  - AIMS: Our previous studies indicate that glycine can inhibit N-methyl-D-aspartate 
      receptor (NMDAR) responses induced by high concentrations of NMDA in rat 
      hippocampal neurons. The present study was designed to observe whether D-serine 
      induces inactivation of NMDARs in cultured rat hippocampal neurons and to 
      investigate the underlying mechanisms of this effect. METHODS: Cell culture, 
      whole-cell patch-clamp electrophysiology, Ca(2+) imaging, immunohistochemistry, 
      and Western blot analysis were used. RESULTS: We found that the peak current and 
      Ca(2+) influx evoked by 30 muM NMDA were increased by co-application of D-serine, 
      but those evoked by 300 muM NMDA were reduced dose-dependently by co-application 
      of D-serine. However, the inhibitory effect of D-serine on NMDAR responses was 
      reversed by ZnCl2 (30 nM), an inhibitor of the NR2A subunit, but was less 
      influenced by ifenprodil (10 muM), an NR2B inhibitor. In addition, the inhibitory 
      effect of D-serine was not detected in young hippocampal neurons that expressed 
      less of the NR2A subunits and reversed in the presence of 10 mM BAPTA. 
      CONCLUSIONS: D-serine can also induce inactivation of NMDARs, the NR2A subunit is 
      required for the induction of this effect, and this inactivation is 
      Ca(2+)-dependent in nature. This action of D-serine is hypothesized to play a 
      neuroprotective role upon a sustained large glutamate insult to the brain.
CI  - (c) 2014 John Wiley & Sons Ltd.
FAU - Li, Xia
AU  - Li X
AD  - Department of Neuropharmacology, Institute of Nautical Medicine, Nantong 
      University, Jiangsu, China.
FAU - Zhang, Yuan-Yuan
AU  - Zhang YY
FAU - Chen, Zhao-Qin
AU  - Chen ZQ
FAU - Jiang, Zheng-Lin
AU  - Jiang ZL
FAU - Sun, Li
AU  - Sun L
FAU - Xu, Li-Hua
AU  - Xu LH
FAU - Yang, Yao
AU  - Yang Y
FAU - Zhang, Yun-Feng
AU  - Zhang YF
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140718
PL  - England
TA  - CNS Neurosci Ther
JT  - CNS neuroscience & therapeutics
JID - 101473265
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Chelating Agents)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Piperidines)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 452VLY9402 (Serine)
RN  - 526U7A2651 (Egtazic Acid)
RN  - 6384-92-5 (N-Methylaspartate)
RN  - K22DDW77C0 (1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid)
RN  - R8OE3P6O5S (ifenprodil)
RN  - SY7Q814VUP (Calcium)
RN  - VH92ICR8HX (N-methyl D-aspartate receptor subtype 2A)
SB  - IM
MH  - Animals
MH  - Calcium/*metabolism
MH  - Calcium Channel Blockers/pharmacology
MH  - Cells, Cultured
MH  - Chelating Agents/pharmacology
MH  - Egtazic Acid/analogs & derivatives/pharmacology
MH  - Embryo, Mammalian
MH  - Excitatory Amino Acid Agonists/pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Hippocampus/cytology
MH  - Membrane Potentials/drug effects
MH  - N-Methylaspartate/pharmacology
MH  - Neurons/*drug effects
MH  - Patch-Clamp Techniques
MH  - Piperidines/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, N-Methyl-D-Aspartate/*metabolism
MH  - Serine/*pharmacology
PMC - PMC6493008
OTO - NOTNLM
OT  - D-serine
OT  - Glycine-dependent inactivation
OT  - Hippocampal neurons
OT  - N-methyl-D-aspartate
OT  - NMDA receptors
OT  - Neuroprotection
COIS- The authors declare no conflict of interest.
EDAT- 2014/07/22 06:00
MHDA- 2015/06/30 06:00
PMCR- 2014/07/18
CRDT- 2014/07/22 06:00
PHST- 2013/11/22 00:00 [received]
PHST- 2014/06/23 00:00 [revised]
PHST- 2014/06/27 00:00 [accepted]
PHST- 2014/07/22 06:00 [entrez]
PHST- 2014/07/22 06:00 [pubmed]
PHST- 2015/06/30 06:00 [medline]
PHST- 2014/07/18 00:00 [pmc-release]
AID - CNS12308 [pii]
AID - 10.1111/cns.12308 [doi]
PST - ppublish
SO  - CNS Neurosci Ther. 2014 Nov;20(11):951-60. doi: 10.1111/cns.12308. Epub 2014 Jul 
      18.