UNIQUE PROPERTIES OF [H-3] MK-801 BINDING IN MEMBRANES FROM THE RAT SPINAL-CORD

In order to investigate possible differences between NMDA receptor-cou pled ion channels in the spinal cord and in the cerebral cortex, we ha ve characterized [H-3]MK-801 ,11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine] binding and its regulation by glutamate and glycine in membr ane preparations of the rat spinal cord and cerebral cortex. The K-D v alue of [H-3]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 compar ed to those in the cerebral cortex, whereas the EC50 values for glutam ate were similar in both regions. The IC50 values of -((3)-2-carboxypi perazin-4-yl)-propyl-1-phosphonic acid (D-CPP) were significantly lowe r in the spinal cord in the presence of saturating concentrations of g lutamate. The IC50 values of hloro-4-hydroxy-3-(3-phenoxy)phenyl-2(H)- quinoline (L-701,324) were significantly lower in the spinal cord unde r all conditions. These results suggest that NMDA receptors in the spi nal cord display low affinity for MK-801, which may correspond to a lo wer affinity of the voltage-dependent Mg2+ block. Furthermore, NMDA re ceptors in the spinal cord appear to display high sensitivity to glyci ne and to glutamate and glycine antagonists.