Lead inhibition of N-methyl-D-aspartate receptors containing NR2A, NR2C and NR2D subunits

Irina A. Omelchenko, Cole S. Nelson, Charles Allen

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 lu va e was 3.39 μM. Pb was a noncompetitive inhibitor of NR1b-2A, NR1b-2C and NR1b-2D NMDA receptors. At low concentrations (2+ 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.

Original languageEnglish (US)
Pages (from-to)1458-1464
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume282
Issue number3
StatePublished - Sep 1997

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N-Methyl-D-Aspartate Receptors
Inhibitory Concentration 50
Glutamic Acid
Xenopus laevis
Oocytes
Lead

ASJC Scopus subject areas

  • Pharmacology

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Lead inhibition of N-methyl-D-aspartate receptors containing NR2A, NR2C and NR2D subunits. / Omelchenko, Irina A.; Nelson, Cole S.; Allen, Charles.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 282, No. 3, 09.1997, p. 1458-1464.

Research output: Contribution to journalArticle

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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 lu va e was 3.39 μM. Pb was a noncompetitive inhibitor of NR1b-2A, NR1b-2C and NR1b-2D NMDA receptors. At low concentrations (2+ 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.

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