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 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.
Footnotes
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Send reprint requests to: Charles N. Allen, Ph.D., CROET, L606, Oregon Health Sciences University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97201-3098. E-mail:allenc{at}ohsu.edu
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↵1 This work was funded by Grant NS19611 from the National Institutes of Health.
- Abbreviations:
- NMDA
- N-methyl-d-aspartate
- Glu
- glutamate
- Hc
- Hill coefficient
- HEPES
- N-[2-hydroxyethyl]piperazine-N′-2-ethanesulfonic acid
- Received December 5, 1996.
- The American Society for Pharmacology and Experimental Therapeutics
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