PMID- 15354184 OWN - NLM STAT- MEDLINE DCOM- 20050126 LR - 20161124 IS - 0893-133X (Print) IS - 0893-133X (Linking) VI - 30 IP - 1 DP - 2005 Jan TI - NAAG reduces NMDA receptor current in CA1 hippocampal pyramidal neurons of acute slices and dissociated neurons. PG - 7-16 AB - N-acetylaspartylglutamate (NAAG) is an abundant neuropeptide in the nervous system, yet its functions are not well understood. Pyramidal neurons of the CA1 sector of acutely prepared hippocampal slices were recorded using the whole-cell patch-clamp technique. At low concentrations (20 microM), NAAG reduced isolated N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic currents or NMDA-induced currents. The NAAG-induced change in the NMDA concentration/response curve suggested that the antagonism was not competitive. However, the NAAG-induced change in the concentration/response curve for the NMDAR co-agonist, glycine, indicated that glycine can overcome the NAAG antagonism. The antagonism of the NMDAR induced by NAAG was still observed in the presence of LY-341495, a potent and selective mGluR3 antagonist. Moreover, in dissociated pyramidal neurons of the CA1 region, NAAG also reduced the NMDA current and this effect was reversed by glycine. These results suggest that NAAG reduces the NMDA currents in hippocampal CA1 pyramidal neurons. FAU - Bergeron, Richard AU - Bergeron R AD - Ottawa Health Research Institute, Ottawa, ON, Canada. rbergeron@ohri.ca FAU - Coyle, Joseph T AU - Coyle JT FAU - Tsai, Guochan AU - Tsai G FAU - Greene, Robert W AU - Greene RW LA - eng GR - MH 51290/MH/NIMH NIH HHS/United States GR - MH606450/MH/NIMH NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Neuropsychopharmacology JT - Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology JID - 8904907 RN - 0 (Dipeptides) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 1W8M12WXYL (isospaglumic acid) RN - TE7660XO1C (Glycine) SB - IM MH - Animals MH - Cell Separation MH - Dipeptides/*pharmacology MH - Dose-Response Relationship, Drug MH - Electric Stimulation MH - Electrophysiology MH - Glycine/pharmacology MH - Hippocampus/cytology/drug effects/*metabolism MH - In Vitro Techniques MH - Neural Conduction/drug effects MH - Neurons/*metabolism MH - Patch-Clamp Techniques MH - Pyramidal Cells/*metabolism MH - Rats MH - Rats, Long-Evans MH - Rats, Sprague-Dawley MH - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors MH - Synapses/drug effects EDAT- 2004/09/09 05:00 MHDA- 2005/01/27 09:00 CRDT- 2004/09/09 05:00 PHST- 2004/09/09 05:00 [pubmed] PHST- 2005/01/27 09:00 [medline] PHST- 2004/09/09 05:00 [entrez] AID - 1300559 [pii] AID - 10.1038/sj.npp.1300559 [doi] PST - ppublish SO - Neuropsychopharmacology. 2005 Jan;30(1):7-16. doi: 10.1038/sj.npp.1300559.