GLYCINE-LIKE MODULATION OF N-METHYL-D-ASPARTATE RECEPTORS BY A MONOCLONAL-ANTIBODY THAT ENHANCES LONG-TERM POTENTIATION

We have identified a monoclonal antibody, B6B21, 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-mu-g of membranes gave a two- to threefold elevation in N-[1-(2-thienyl)cyclohexyl]-3,4-[H-3]piperidine ([H-3]TCP) binding. When [H-3]TCP binding was stimulated by the combined addition of maximal concentrations of glutamate, glycine, and magnesium, B6B21 no longer stimulated [H-3]TCP binding. Like glycine, B6B21 enhanced the effect of N-methyl-D-aspartate and glutamate in stimulating [H-3]TCP binding. Moreover, B6B21 reversed 7-chlorokynurenic acid inhibition of [H-3]TCP binding, but it had no effect on the inhibition of [H-3]TCP binding by D-(-)-2-amino-5-phosphonovaleric acid. B6B21 increased the rate of association and dissociation of [H-3]TCP, but had no effect on equilibrium binding. Glutamate, but not glycine, however, increased B6B21-enhancement of [H-3]TCP association and dissociation. B6B21 binding at strychnine-insensitive glycine sites was confirmed by direct measurement of [H-3]glycine binding. These results suggest that B6B21 binds directly to N-methyl-D-aspartate receptors and displays properties similar to glycine.