Pharmacological characterization of [3H]MK-801 binding in the rat spinal cord

Abstract Using a receptor binding assay for [ 3 H](+)-5-methyl-10,11-dihydro-5 H -dibenzo[ a,d ]cyclohepten-5-10-imine (MK-801) the pharmacology of spinal cord NMDA receptors was compared to that of NMDA receptors in the cerebral cortex. The affinities of glutamate site agonists l -glutamate, l -aspartate, ibotenic acid, NMDA and quinolinic acid for stimulation of [ 3 H]MK-801 binding were 6–10 times lower in the spinal cord and the efficacy of quinolinic acid was 50% of that of the other agonists in this region. Also the 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 dextromethorphan. The divalent cations Zn 2+ , Mg 2+ and Ca 2+ had 4–8 times lower affinity for spinal NMDA receptors while the affinity of Co 2+ was 50 times lower. The affinity of [ 3 H]MK-801 was 2.5-fold lower in the spinal cord. These data show that spinal cord NMDA receptors show qualitative and quantitative differences compared to those in the cerebral cortex.