Polyamine and redox modulation of [H-3]MK-801 binding to N-methyl-D-aspartate receptors in the spinal cord and cerebral cortex

The pharmacology of N-methyl-D-aspartate (NMDA) receptors shows regional di fferences in affinity for various agonists and antagonists. We have investi gated the modulatory mechanisms acting via the polyamine, redox and proton sites in the cerebral cortex and the spinal cord of adult, male rats using [H-3]MK-801 binding. The affinity for glycine-independent spermine stimulat ion was one magnitude higher in cerebrocortical than in spinal cord membran es while the affinity for the spermine antagonist arcaine was similar. Sper mine abolished the inhibiting effect of low pH in both regions. Thus, the d ifference in the polyamine site between the two regions seems to be restric ted to agonist binding. The proportion of high affinity/total ifenprodil bi nding was approximate to 35% both in the spinal cord and the cerebral corte x, suggesting similar relative amounts of the NMDA receptor subunit 2B. The affinity of ifenprodil to the high affinity site was however significantly higher in the cerebral cortex. Redox modulatory agents had similar effects in the two regions but spermine fully counteracted the inhibiting effect o f 0.2 mM 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB) in the cerebral cortex while there was only a partial effect in the spinal cord. These data show that the regional pharmacological heterogeneity involves several of the mec hanisms regulating the function of the NMDA receptor. The data also indicat e that the NMDA receptor subunit 2B is much more common in spinal cord than previously suggested.