Characterization of the effects of polyamines on the modulation of the N-methyl-D-aspartate receptor by glycine.
We have investigated the effects of polyamine agonists and antagonists on the modulation of the N-methyl-D- aspartate receptor by glycine using a [3H]dizocilpine ([3H]MK801) binding assay. We monitored the non-equilibrium binding of [3H]dizocilipine in the presence of 5,7-dichlorokynurenate to preclude occupation of the glycine site by endogenous glycine. Using this assay, spermine and spermidine increased both the affinity and the maximum effect of glycine. Similar effects are produced by other polyamine agonists including 1,5-diethylaminopiperidine, neomycin and Ca2+. These actions are reversed by the polyamine glycine produced by polyamine agonists appears to be due to an increase in the equilibrium affinity of [3H]dizocilpine, and cannot therefore be attributed solely to modulation of glycine binding. Interestingly, 1,5-diethylaminopiperidine increases the maximum effect of glycine to a greater extent than it alters glycine affinity, suggesting that the two effects may be mediated by different sites or mechanisms. These studies will help to define the role of the glycine site in the modulation of the N-methyl-D-aspartate receptor by polyamines.
Department of Pharmacology, University of Pittsburgh, PA 15261, USA.
I J
IJ
Reynolds
K D
KD
Rothermund
D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D001667:Binding, Competitive; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000494:pharmacology*; D011073:Polyamines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*
D001645:Biguanides; D011073:Polyamines; D016194:Receptors, N-Methyl-D-Aspartate; C006624:arcaine; D016291:Dizocilpine Maleate; D005998:Glycine