Unique properties of [3H]MK-801 binding in membranes from the rat spinal cord.
In order to investigate possible differences between NMDA receptor-coupled ion channels in the spinal cord and in the cerebral cortex, we have characterized [3H]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 [3H]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 D-((3)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (D-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.
Liu
Y
Y
Department of Neuroscience, Karolinska Institutet, Stockholm, Sweden.
Souverbie
F
F
Sundström
E
E
von Euler
G
G
D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D008297:Male; D008566:Membranes / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium
D018691:Excitatory Amino Acid Antagonists; D010879:Piperazines; D015363:Quinolones; D014316:Tritium; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C094635:L 701324; D005998:Glycine