Antagonistic action on NMDA/GluN2B mediated currents of two peptides that were conantokin-G structure-based designed

BMC Neuroscience
Edwin A Reyes-GuzmanEsperanza Recio-Pinto

Abstract

The GluN2B subunit of the N-methyl-D-aspartate receptor (NMDAr) modulates many physiological processes including learning, memory, and pain. Excessive increase in NMDAr/GluN2B activity has been associated with various disorders such neuropathic pain and neuronal death following hypoxia. Thus there is an interest in identifying NMDAr antagonists that interact specifically with the GluN2B subunit. Recently based on structural analysis between the GluN2B subunit and conantokin-G, a toxin that interacts selectively with the GluN2B subunit, we designed various peptides that are predicted to act as NMDAr antagonists by interacting with the GluN2B subunit. In this study we tested this prediction for two of these peptides EAR16 and EAR18. The effects of EAR16 and EAR18 in NMDA-evoked currents were measured in cultured rat embryonic hippocampal neurons and in HEK-293 cells expressing recombinant NMDAr comprised of GluN1a-GluN2A or GluN1a-GluN2B subunits. In hippocampal neurons, EAR16 and EAR18 reduced the NMDA-evoked calcium currents in a dose-dependent and reversible manner with comparable IC50 (half maximal inhibitory concentration) values of 241 and 176 µM, respectively. At 500 µM, EAR16 blocked more strongly the NMDA-evoked currents...Continue Reading

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Citations

Mar 6, 2019·Marine Drugs·Rachael A MansbachS Gnanakaran

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Methods Mentioned

BETA
transfection
NMR

Software Mentioned

AutoDock Vina
FlexPepDock
GraphPadPrism
Rosetta
TASSER
Autodock Tools
Ensembl
Rosetta FlexPepDock server
UCSF Chimera
Discovery Studio Visualizer

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