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

BMC Neuroscience

Research Article

Esperanza Recio-Pinto¹  Edwin A. Reyes-Guzman²  Edgar A. Reyes-Montaño³  Nohora Vega-Castro³ 

[1] Department of Anesthesiology, Perioperative Care and Pain Medicine, NYU Langone Medical Center, 180 Varick Street, Room 677, 10014, New York, NY, USA;Department of Anesthesiology, Perioperative Care and Pain Medicine, NYU Langone Medical Center, 180 Varick Street, Room 677, 10014, New York, NY, USA;Grupo de Investigación en Proteínas, Departamento de Química, Universidad Nacional de Colombia, Cra 30 No 45-03 Edificio 451 Lab 201-1, Bogotá, Colombia;Grupo de Investigación en Proteínas, Departamento de Química, Universidad Nacional de Colombia, Cra 30 No 45-03 Edificio 451 Lab 201-1, Bogotá, Colombia;

关键词: NMDA;    Conantokin-G;    Hippocampal neurons;    GluN2B;    GluN2A;   

DOI  :  10.1186/s12868-017-0361-4

 received in 2016-10-21, accepted in 2017-05-04,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe 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.ResultsThe 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 mediated by the GluN1a–GluN2B (84%) than those mediated by the GluN1a–GluN2A (50%) subunits. At 500 µM, EAR18 blocked to a similar extent the NMDA-evoked currents mediated by the GluN1a–GluN2B (62%) and the GluN1a–GluN2A (55%) subunits.ConclusionsThe newly designed EAR16 and EAR18 peptides were shown to block in reversible manner NMDA-evoked currents, and EAR16 showed a stronger selectivity for GluN2B than for GluN2A.

【 授权许可】

CC BY   
© The Author(s) 2017