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Subunit-dependent inhibition of recombinant rodent N-methyl-D-aspartate receptors by a HIV-1 glycoprotein 120 derived peptide.

Wittekindt, B. and Betz, H. and Laube, Bodo (2000):
Subunit-dependent inhibition of recombinant rodent N-methyl-D-aspartate receptors by a HIV-1 glycoprotein 120 derived peptide.
In: Neuroscience letters, pp. 151-4, 280, (2), ISSN 0304-3940, [Article]

Abstract

Considerable evidence suggests that low (picomolar) concentrations of the HIV-1 envelope glycoprotein gp120 induce neuronal cell death by stimulating the release of microglial toxins, which in turn activate N-methyl-D-aspartate (NMDA) receptors. Conversely, high (micromolar) concentrations of gp120 have been reported to directly inhibit NMDA receptor-mediated currents and do not induce neurotoxicity. Here we show that micromolar concentrations of a synthetic peptide corresponding to the V3-loop of gp120 (V3-pep) inhibited agonist responses of recombinant heteromeric rodent NMDA receptors expressed in Xenopus laevis oocytes by decreasing their apparent glycine affinity. Different combinations of NMDA receptor subunits displayed differential sensitivities to inhibition by V3-pep, with a potency rank order of NR1/2B > NR1/2D > NR1/2C > or = NR1/2A. Our observations may provide an explanation for the reduced neurotoxicity of high doses of gp120 in cell cultures and may be useful for the pharmacological discrimination of NMDA receptor subtypes.

Item Type: Article
Erschienen: 2000
Creators: Wittekindt, B. and Betz, H. and Laube, Bodo
Title: Subunit-dependent inhibition of recombinant rodent N-methyl-D-aspartate receptors by a HIV-1 glycoprotein 120 derived peptide.
Language: English
Abstract:

Considerable evidence suggests that low (picomolar) concentrations of the HIV-1 envelope glycoprotein gp120 induce neuronal cell death by stimulating the release of microglial toxins, which in turn activate N-methyl-D-aspartate (NMDA) receptors. Conversely, high (micromolar) concentrations of gp120 have been reported to directly inhibit NMDA receptor-mediated currents and do not induce neurotoxicity. Here we show that micromolar concentrations of a synthetic peptide corresponding to the V3-loop of gp120 (V3-pep) inhibited agonist responses of recombinant heteromeric rodent NMDA receptors expressed in Xenopus laevis oocytes by decreasing their apparent glycine affinity. Different combinations of NMDA receptor subunits displayed differential sensitivities to inhibition by V3-pep, with a potency rank order of NR1/2B > NR1/2D > NR1/2C > or = NR1/2A. Our observations may provide an explanation for the reduced neurotoxicity of high doses of gp120 in cell cultures and may be useful for the pharmacological discrimination of NMDA receptor subtypes.

Journal or Publication Title: Neuroscience letters
Volume: 280
Number: 2
Divisions: 10 Department of Biology
10 Department of Biology > Neurophysiology and Neurosensory Systems
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Date Deposited: 12 Apr 2011 08:04
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