MOLECULAR PHARMACOLOGY, 36:836-839 ACCELERA TED COMMUNICATION 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 EC of 27 ± 3.1 M. 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-aspar-tate receptor antagonists. Furthermore, spermine produced a leftward shift in the IC83 of glycine agonists in displacing [3H] glycine binding, without altering the lC 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. Polyamines are ubiquitously distributed in body tissue. Th