Unique properties of [

In order to investigate possible differences between NMDA receptor-coupled ion channels in the spinal cord and in the cerebral cortex, we have characterized [

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]MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine] binding and its regulation by glutamate and glycine in membrane preparations of the rat spinal cord and cerebral cortex. The K_D value of [

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]MK-801 binding was higher in the spinal cord than in the cerebral cortex, mainly due to a lower association rate constant. When corrected for the concentrations of residual endogenous amino acids, the EC₅₀ values for glycine were lower at spinal NMDA receptors compared to those in the cerebral cortex, whereas the EC₅₀ values for glutamate were similar in both regions. The IC₅₀ values of

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-((3)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (

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-CPP) were significantly lower in the spinal cord in the presence of saturating concentrations of glutamate. The IC₅₀ values of 7-chloro-4-hydroxy-3-(3-phenoxy)phenyl-2(H)-quinoline (L-701,324) were significantly lower in the spinal cord under all conditions. These results suggest that NMDA receptors in the spinal cord display low affinity for MK-801, which may correspond to a lower affinity of the voltage-dependent Mg²⁺ block. Furthermore, NMDA receptors in the spinal cord appear to display high sensitivity to glycine and to glutamate and glycine antagonists.