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 micrograms 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-chlorokynurenic 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.
Haring
R
R
Department of Neurological Surgery, Albert Einstein College of Medicine, Bronx, New York.
Stanton
P K
PK
Scheideler
M A
MA
Moskal
J R
JR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism / Q000502:physiology*; D001921:Brain / Q000378:metabolism; D005998:Glycine / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism / Q000502:physiology*; D013570:Synaptic Membranes / Q000378:metabolism
D000911:Antibodies, Monoclonal; D016194:Receptors, N-Methyl-D-Aspartate; C012058:tenocyclidine; D010622:Phencyclidine; D005998:Glycine