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.
Sacaan
A I
AI
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77550.
Johnson
K M
KM
D000818:Animals; D003986:Dibenzocycloheptenes / Q000378:metabolism; D016291:Dizocilpine Maleate; D005998:Glycine / Q000378:metabolism*; D007700:Kinetics; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008274:Magnesium / Q000494:pharmacology; D051381:Rats; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D013096:Spermine / Q000494:pharmacology*
D003986:Dibenzocycloheptenes; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D013096:Spermine; D016291:Dizocilpine Maleate; D007736:Kynurenic Acid; D008274:Magnesium; C057013:7-chlorokynurenic acid; D005998:Glycine