Neuroreport 1996 Dec 20;81:257-9. doi: 10.1097/00001756-199612200-00051.

Competitive antagonism of recombinant AMPA/kainate receptors by N-methyl-D-aspartate and analogues.

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The classical division of mammalian ionotropic L-glutamate (Glu) receptors into N-methyl-D-aspartate (NMDA) and non-NMDA classes is supported by a wealth of biochemical and molecular biological data. In binding studies, selective agonists for non-NMDA receptors such as L-kainate (KA), alpha-amino-3-hydroxy-5-methylisoxazole-propionate (AMPA) and L-domoate have submicromolar affinities; in contrast, a millimolar concentration of NMDA is required significantly to compete with the non-NMDA agonists. Despite the supposed clear-cut selectivities of these amino acids, interactions between the responses to submillimolar concentrations of NMDA and KA have been observed in cells expressing both classes of Glu receptor. We present here evidence that NMDA is a competitive antagonist of recombinant non-NMDA receptors. We also present preliminary data on competitive antagonism of recombinant NMDA receptors by KA. These antagonisms are inhibited non-competitively by cyclothiazide and a benzodiazipine.

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