Pharmacological characterization of the N-methyl-D-aspartate (NMDA) receptor-channel in rodent and dog brain and rat spinal cord using [3H]MK-801 binding.

The biochemical and pharmacological properties of [3H]MK-801 binding to the N-methyl-D-aspartate (NMDA) receptor-channel in homogenates of mouse, guinea pig and dog brain, dog cerebral cortex and rat spinal cord were determined using radioligand binding techniques. Specific [3H]MK-801 binding increased linearly with increasing tissue concentration and in general represented 80-93% of the total binding at 6-8 nM radioligand concentration. [3H]MK-801 interacted with brain and spinal homogenates with high affinity. The dissociation constants (KD) for all tissues studied were similar ranging between 7.9 and 11.9 nM, whereas the maximum number of binding sites (Bmax) showed a wide, tissue-dependent range (0.1-6.75 pmol/mg protein). The rank order of tissue enrichment was found to be as follows: mouse brain much greater than dog cerebral cortex much greater than dog brain much greater than guinea pig brain much greater than rat spinal cord. Specific [3H]MK-801 binding in rodent and dog brain, dog cerebral cortex and rat spinal cord exhibited a similar pharmacological profile (correlation coefficients = 0.93-0.99). The rank order of potency of unlabelled compounds competing for [3H]MK-801 binding was: (+)MK-801 greater than (-)MK-801 greater than phencyclidine greater than (-)cyclazocine much greater than (+)cyclazocine greater than or equal to ketamine greater than (+)N-allyl-N-normetazocine greater than (-)N-allyl-N-normetazocine greater than (-)pentazocine greater than (+)pentazocine. NMDA, Kainate, quisqualate and several other compounds failed to inhibit [3H]MK-801 binding at 100 microM.(ABSTRACT TRUNCATED AT 250 WORDS)