Modulation by magnesium of N-methyl-D-aspartate receptors in developing human brain
a School of Biological Sciences, University of Manchester, b Department of Child Health, c School of Pathological Sciences
Correspondence to: Dr P Slater, School of Biological Sciences, 1.124 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT.
Accepted 18 September 1997
AIM
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.
METHODSThe 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.
RESULTSNeonatal 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 µM) and glycine (10 µM) 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.
CONCLUSIONInfant 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.
© 1998 by Archives of Disease in Childhood
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