Glycine‐Like Modulation of N‐Methyl‐d‐Aspartate Receptors by a Monoclonal Antibody That Enhances Long‐Term Potentiation

Abstract: We have identified a monoclonal antibody, B6 B21, that significantly elevates long‐term potentiation when applied to CA1 pyramidal cell apical dendrites in rat hippocampal slices and characterized its binding to N‐methyl‐d‐aspartate‐receptor complexes using extensively washed hippocampal membranes. Five micrograms of affinity‐purified B6B21 per 100 μg of membranes gave a two‐to threefold elevation in N‐[1‐(2‐thienyl)cyclohexyl]‐3,4‐[³H]piperidine ([³H]TCP) binding. When [³H]TCP binding was stimulated by the combined addition of maximal concentrations of glutamate, glycine, and magnesium, B6B21 no longer stimulated [³H]TCP binding. Like glycine, B6B21 enhanced the effect of N‐methyl‐d‐aspartate and glutamate in stimulating [³H]TCP binding. Moreover, B6B21 reversed 7‐chlorokyn‐urenic acid inhibition of [³H]TCP binding, but it had no effect on the inhibition of [³H]TCP binding by d‐(−)‐2‐amino‐5‐phosphonovaleric acid. B6B21 increased the rate of association and dissociation of [³H]TCP, but had no effect on equilibrium binding. Glutamate, but not glycine, however, increased B6B21‐enhancement of [³H]TCP association and dissociation. B6B21 binding at strychnine‐insensitive glycine sites was confirmed by direct measurement of [³H]glycine binding. These results suggest that B6B21 binds directly to N‐methyl‐d‐aspartate receptors and displays properties similar to glycine.