In Vitro Metal Inhibition of N-Methyl-D-Aspartate Specific Glutamate Receptor Binding in Neonatal and Adult Rat Brain

Abstract

The in vitro effect of methyl mercury (MM) and lead (Pb) on N-methyl-D-aspartate (NMDA)-specific glutamate receptor binding in neonatal (10 days old) and adult rat brain was investigated. The cerebral cortex was isolated from the neonatal and adult male Sprague-Dawley rats and the synaptic plasma membranes were prepared to study the NMDA-specific glutamate receptor binding by using (3H)-glutamic acid. The metal salts such as methyl mercury chloride and lead acetate were used to study the effect of MM and Pb. Both MM and Pb significantly inhibited the receptor binding in neonatal and adult rat brain in a concentration-dependent manner. MM (IC50:0.95 +/- 0.08 microM) was more potent in inhibiting the receptor binding than Pb (IC50:60 +/- 7 microM) in neonatal rat brain. A similar high potency was observed for MM than Pb in adult rat brain but the IC50 values are very high (70 +/- 6 microM and 300 +/- 24 microM respectively) indicating less effect compared to neonatal brain. The data suggest that NMDA-receptor binding was more sensitive to MM and Pb in neonatal brain than in adult. MM was more effective than Pb because of its more lipophilicity.