RT Journal Article SR Electronic T1 Lead Inhibition of N-Methyl-d-aspartate Receptors Containing NR2A, NR2C and NR2D Subunits JF Journal of Pharmacology and Experimental Therapeutics JO J Pharmacol Exp Ther FD American Society for Pharmacology and Experimental Therapeutics SP 1458 OP 1464 VO 282 IS 3 A1 Irina A. Omelchenko A1 Cole S. Nelson A1 Charles N. Allen YR 1997 UL http://jpet.aspetjournals.org/content/282/3/1458.abstract AB The potency of Pb2+ inhibition of glutamate-activated currents mediated by N-methyl-d-aspartate (NMDA) receptors was dependent on the subunits composing the receptors when functionally expressed in Xenopus laevis oocytes. Pb2+reduced the amplitudes of glutamate-activated currents and shifted the agonist EC50 values of NMDA receptors consisting of different subunit compositions. The IC50 values for Pb2+ ranged from 1.52 to 8.19 μM, with a rank order of potency of NR1b-2A > NR1b-2C > NR1b-2D > NR1b-2AC. For NR1b-2AC NMDA receptors, the IC50 value was dependent on the agonist concentration; at saturating agonist concentrations (300 μM), the IC50 value was 8.19 μM, whereas at 3 μM glutamate, the IC50 value was 3.39 μM. Pb2+was a noncompetitive inhibitor of NR1b-2A, NR1b-2C and NR1b-2D NMDA receptors. At low concentrations (<1 μM) Pb2+potentiated NR1b-2AC NMDA receptors. These data provide further evidence to support the hypothesis that the actions of Pb2+on NMDA receptors are determined by the receptor subunit composition. The American Society for Pharmacology and Experimental Therapeutics