Modulation by magnesium of N-methyl-D-aspartate receptors in developing human brain.
OBJECTIVE
To investigate age related alterations in glutamate N-methyl-D-aspartate (NMDA) receptor binding produced by the modulatory compounds glutamate, glycine, and magnesium (Mg2+) sulphate.


METHODS
The effects produced by glutamate plus glycine, and Mg2+ on the binding of [3H]MK-801, a ligand for the N-methyl-D-aspartate ion channel phencyclidine site, were measured in membrane preparations made from prefrontal cortex from human neonate (n = 5), infant (n = 6), and adult (n = 6) necropsy brains.


RESULTS
Neonatal brains had the least [3H]MK-801 binding, suggesting either a low density of NMDA receptors or a more restricted access of [3H]MK-801 to cation channel sites. Infant brains had the most [3H]MK-801 binding which was stimulated to a greater extent by L-glutamate (100 microM) and glycine (10 microM) than in neonatal and adult brains. MG2+ invariably inhibited [3H]MK-801 binding. However, the Mg2+ IC50 value was higher in neonatal brain (3.6 mM) than infant (1.4 mM) and adult (0.87 mM) brains.


CONCLUSIONS
Infant brain may have excess NMDA receptors which are hyper responsive to glutamate and glycine. The lower potency of Mg2+ to inhibit [3H]MK-801 binding in neonatal cortex may be because newborn babies have NMDA receptors without the normal complement of Mg2+ sites. The findings suggest that therapeutic NMDA receptor block in neonates requires higher concentrations of magnesium sulphate in brain tissue.
Chahal
H
H
School of Biological Sciences, University of Manchester.
D'Souza
S W
SW
Barson
A J
AJ
Slater
P
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism*; D005260:Female; D005971:Glutamates / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007234:Infant, Premature / Q000378:metabolism; D008278:Magnesium Sulfate / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects* / Q000378:metabolism
D005971:Glutamates; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D008278:Magnesium Sulfate; D005998:Glycine