Spermine enhances binding to the glycine site associated with the N-methyl-D-aspartate receptor complex.

Spermine enhanced strychnine-insensitive [3H]glycine binding 3-fold with an EC50 of 27 +/- 3.1 microM. Spermidine and putrescine were without effect, whereas the ethylenediamine analog of spermine had an intermediate effect. Eadie-Hofstee analysis revealed that spermine increased the affinity of glycine for its receptor without a significant change in receptor density. This effect persisted in the presence of glycine or N-methyl-D-aspartate receptor antagonists. Furthermore, spermine produced a leftward shift in the IC50 of glycine agonists in displacing [3H]glycine binding, without altering the IC50 for glycine antagonists. These data indicate that spermine interacts with the glycine receptor through a novel binding site and, further, that spermine can be used to discriminate glycine agonist and antagonist binding.