Modulation by magnesium of N-methyl-D-aspartate receptors in developing human brain
- aSchool of Biological Sciences, University of Manchester, bDepartment of Child Health, cSchool of Pathological Sciences
- Dr P Slater, School of Biological Sciences, 1.124 Stopford Building, University of Manchester, Oxford Road, Manchester M13 9PT.
- Accepted 18 September 1997
Abstract
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.
METHODS The effects produced by glutamate plus glycine, and Mg2+ on the binding of [3H]MK-801, a ligand for theN-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 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.
CONCLUSION 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.
