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 usi ng a [H-3]dizocilpine ([H-3]MK801) binding assay. We monitored the non -equilibrium binding of [H-3]dizocilpine in the presence of 5,7-dichlo rokynurenate 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 produc ed by other polyamine agonists including 1,5-diethylaminopiperidine, n eomycin and Ca2+. These actions are reversed by the polyamine antagoni sts arcaine and 1,10-diaminodecane in a competitive manner. The increa se in the maximum effect of glycine produced by polyamine agonists app ears to be due to an increase in the equilibrium affinity of [H-3]dizo cilpine, and cannot therefore be attributed solely to modulation of gl ycine 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 th e glycine site in the modulation of the N-methyl-D-aspartate receptor by polyamines.