In an attempt to investigate the role of polyamines, spermine and spermidine, which may be involved in synaptic mechanism of central neurotransmission in the N-methyl-D-aspartate (NMDA) receptor, the authors performed receptor binding assay using (3H) 5-methyl-10, 11- dihydro-5H-dibenzoCa, d) -cycloheptene-5, 10-imine maleate which is known to selectively antagonize the NMDA receptor in noncompetitive fashion in order to know the effects of reciprocal interactions between glutamate, glycine, and polyamines on [3H)MK-801 binding to rat brain membrane. The results are summarized as follows : 1) Polyamines, spermine and spermidine, enhanced the binding of (3H〕MK-801 to rat brain membranes as well as glutamate and glycine, and both were similary efficacious. 2) Both spermine and spermidine showed maximal stimulatory effect of C3H]MK-801 binding to rat brain membranes near the concentrations of 100|iM respectively, and maximally active concentrations of spermine and spermidine were reduced to 50jiM respectively in the presence of lOOjiM glutamate and 30(iM glycine. 3) Spermine and spermidine did not affect Bmax of (3H)MK-801 to rat brain membranes, but diminished Kd value. 4) (3H)MK-801 bindings to rat brain membranes were increased by the reciprocal interactions between glutamate, glycine, and polyamines, but maximal stimulatory effect was obtainable in the presence of 100|iM glutamate, 30jiM glycine, and 100uM spermidine. 5) In inhibition experiment of (3HMK-801, IC50 of (3H)MK-801 in the presence of 30uM glycine, lOOuM glutamate or 100u spermine respectively, were not significantly different from control condition (no added glutamate, glycine, and polyamines). In conclusion, these results indicate that the enhancement of C3H)MK-801 binding to rat brain membranes produced by glutamate, glycine, and poly amines (spermine and spermidine) is mediated by three distnct sites which may be allosterically coupled.
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