PHARMACOLOGICAL CHARACTERIZATION OF [H-3] MK-801 BINDING IN THE RAT SPINAL-CORD

Using a receptor binding assay for 0,11-dihydro-5H-dibenzo[a,d]cyclohe pten-5-10-imine (MK-801) the pharmacology of spinal cord NMDA receptor s was compared to that of NMDA receptors in the cerebral cortex. The a ffinities of glutamate site agonists L-glutamate, L-aspartate, iboteni c acid, NMDA and quinolinic acid for stimulation of [H-3]MK-801 bindin g were 6-10 times lower in the spinal cord and the efficacy of quinoli nic acid was 50% of that of the other agonists in this region. Also th e affinities of glycine site agonists glycine, D-serine, D-alanine and L-serine were lower in the spinal cord as were the affinities of the non-competitive antagonists phencyclidine, (+/-)-cyclazocine and dextr omethorphan. The divalent cations Zn2+, Mg2+ and Ca2+ had 4-8 times lo wer affinity for spinal NMDA receptors while the affinity of Co2+ was 50 times lower. The affinity of [H-3]MK-801 was 2.5-fold lower in the spinal cord. These data show that spinal cord NMDA receptors show qual itative and quantitative differences compared to those in the cerebral cortex.