PMID- 9861038 OWN - NLM STAT- MEDLINE DCOM- 19990128 LR - 20190501 IS - 0027-8424 (Print) IS - 1091-6490 (Electronic) IS - 0027-8424 (Linking) VI - 95 IP - 26 DP - 1998 Dec 22 TI - Modulation of N-methyl-D-aspartate receptor function by glycine transport. PG - 15730-4 AB - The recent discovery of glycine transporters in both the central nervous system and the periphery suggests that glycine transport may be critical to N-methyl-D-aspartate receptor (NMDAR) function by controlling glycine concentration at the NMDAR modulatory glycine site. Data obtained from whole-cell patch-clamp recordings of hippocampal pyramidal neurons, in vitro, demonstrated that exogenous glycine and glycine transporter type 1 (GLYT1) antagonist selectively enhanced the amplitude of the NMDA component of a glutamatergic excitatory postsynaptic current. The effect was blocked by 2-amino-5-phosphonovaleric acid and 7-chloro-kynurenic acid but not by strychnine. Thus, the glycine-binding site was not saturated under the control conditions. Furthermore, GLYT1 antagonist enhanced NMDAR function during perfusion with medium containing 10 microM glycine, a concentration similar to that in the cerebrospinal fluid in vivo, thereby supporting the hypothesis that the GLYT1 maintains subsaturating concentration of glycine at synaptically activated NMDAR. The enhancement of NMDAR function by specific GLYT1 antagonism may be a feasible target for therapeutic agents directed toward diseases related to hypofunction of NMDAR. FAU - Bergeron, R AU - Bergeron R AD - Laboratory of Neuroscience, Department of Psychiatry, Harvard Medical School, 115 Mill Street, Belmont, MA 02178-9106, USA. FAU - Meyer, T M AU - Meyer TM FAU - Coyle, J T AU - Coyle JT FAU - Greene, R W AU - Greene RW LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PL - United States TA - Proc Natl Acad Sci U S A JT - Proceedings of the National Academy of Sciences of the United States of America JID - 7505876 RN - 0 (Amino Acid Transport Systems, Neutral) RN - 0 (Carrier Proteins) RN - 0 (Excitatory Amino Acid Antagonists) RN - 0 (Glycine Plasma Membrane Transport Proteins) RN - 0 (Quinoxalines) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 0 (Slc6a9 protein, rat) RN - 62T278S1MX (FG 9041) RN - 76726-92-6 (2-Amino-5-phosphonovalerate) RN - TE7660XO1C (Glycine) RN - Y37615DVKC (Bicuculline) SB - IM MH - 2-Amino-5-phosphonovalerate/pharmacology MH - *Amino Acid Transport Systems, Neutral MH - Animals MH - Bicuculline/pharmacology MH - Carrier Proteins/antagonists & inhibitors/*physiology MH - Electric Stimulation MH - Excitatory Amino Acid Antagonists/*pharmacology MH - *Excitatory Postsynaptic Potentials/drug effects MH - Glycine/*physiology MH - Glycine Plasma Membrane Transport Proteins MH - Hippocampus/*physiology MH - In Vitro Techniques MH - Patch-Clamp Techniques MH - Pyramidal Cells/*physiology MH - Quinoxalines/pharmacology MH - Rats MH - Receptors, N-Methyl-D-Aspartate/*physiology PMC - PMC28112 EDAT- 1998/12/23 00:00 MHDA- 1998/12/23 00:01 PMCR- 1999/06/22 CRDT- 1998/12/23 00:00 PHST- 1998/12/23 00:00 [pubmed] PHST- 1998/12/23 00:01 [medline] PHST- 1998/12/23 00:00 [entrez] PHST- 1999/06/22 00:00 [pmc-release] AID - 4050 [pii] AID - 10.1073/pnas.95.26.15730 [doi] PST - ppublish SO - Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15730-4. doi: 10.1073/pnas.95.26.15730.