Kynurenine and glycine enhance neuronal sensitivity to N-methyl-D-aspartate.
Neurones in rat hippocampal slices were excited by microiontophoretic applications of N-methyl-D-aspartate (NMDA) and kainate. Responses to NMDA were potentiated by glycine 300 microM or 1 mM in the perfusing medium. A small potentiation of kainate was not observed in the presence of the NMDA antagonist 2-amino-5-phosphonopentanoic acid (2AP5). The potentiation of NMDA responses by glycine was not prevented by strychnine 5 or 30 microM and was also shown by D-serine and L-kynurenine but not L-leucine. If sensitivity to NMDA was reduced by kynurenic acid, glycine and L-kynurenine produced a greater enhancement of NMDA. The requirement of NMDA receptor activation for the occupation of strychnine-resistant glycine sites can thus be demonstrated in complex systems such as brain slices. It is possible that L-kynurenine may also be an endogenous ligand capable of modulating NMDA sensitivity.
Stone
T W
TW
Department of Pharmacology, University of Glasgow, Scotland.
D000818:Animals; D004357:Drug Synergism; D005998:Glycine / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects; D007737:Kynurenine / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D013331:Strychnine / Q000494:pharmacology
D007737:Kynurenine; D016202:N-Methylaspartate; D013331:Strychnine; D005998:Glycine