Abstract
The independent and combined effects of Ca 2+, Mg 2+, Zn 2+, Al 3+ and Li + on [ 3H]MK-801 binding in human cerebral cortical membranes were studied to further characterize the modulatory effects of metal ions on the N-methyl- d-aspartate (NMDA) receptor-ionophore. Glycine, in the presence of glutamate, significantly intensified the Mg 2+ inhibition of [ 3H]MK-801 binding whereas it masked the Ca 2+ enhancement and slightly diminished the Zn 2+ inhibition. Both Ca 2+ and Mg 2+ reduced the Zn 2+ inhibitory potency. Aluminum demonstrated a potent, relatively glycine-insensitive inhibition of [ 3H]MK-801 binding as an amorphous Al(OH) 3 polymer rather than as the free ion. Cationic modulation of the NMDA receptor-ionophore appears to be regulated at multiple sites which have significant allosteric interactions.
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