Modulatory effects of aluminum, calcium, lithium, magnesium, and zinc ions on [3H]MK-801 binding in human cerebral cortex.
The independent and combined effects of Ca2+, Mg2+, Zn2+, Al3+ 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 Mg2+ inhibition of [3H]MK-801 binding whereas it masked the Ca2+ enhancement and slightly diminished the Zn2+ inhibition. Both Ca2+ and Mg2+ reduced the Zn2+ 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.
Hubbard
C M
CM
Department of Chemistry, University of Virginia, Charlottesville 22908.
Redpath
G T
GT
Macdonald
T L
TL
VandenBerg
S R
SR
D000293:Adolescent; D000535:Aluminum / Q000494:pharmacology*; D002413:Cations, Divalent / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003986:Dibenzocycloheptenes / Q000378:metabolism*; D016291:Dizocilpine Maleate; D006801:Humans; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*
D002413:Cations, Divalent; D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D016291:Dizocilpine Maleate; D008094:Lithium; D000535:Aluminum