PMID- 28511693
OWN - NLM
STAT- MEDLINE
DCOM- 20180110
LR  - 20181113
IS  - 1471-2202 (Electronic)
IS  - 1471-2202 (Linking)
VI  - 18
IP  - 1
DP  - 2017 May 16
TI  - Antagonistic action on NMDA/GluN2B mediated currents of two peptides that were 
      conantokin-G structure-based designed.
PG  - 44
LID - 10.1186/s12868-017-0361-4 [doi]
LID - 44
AB  - BACKGROUND: 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. RESULTS: 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 microM, respectively. At 500 microM, 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 microM, EAR18 blocked to a similar extent the 
      NMDA-evoked currents mediated by the GluN1a-GluN2B (62%) and the GluN1a-GluN2A 
      (55%) subunits. CONCLUSIONS: The 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.
FAU - Reyes-Guzman, Edwin A
AU  - Reyes-Guzman EA
AD  - Department of Anesthesiology, Perioperative Care and Pain Medicine, NYU Langone 
      Medical Center, 180 Varick Street, Room 677, New York, NY, 10014, USA.
AD  - Grupo de Investigacion en Proteinas, Departamento de Quimica, Universidad 
      Nacional de Colombia, Cra 30 No 45-03 Edificio 451 Lab 201-1, Bogota, Colombia.
FAU - Vega-Castro, Nohora
AU  - Vega-Castro N
AD  - Grupo de Investigacion en Proteinas, Departamento de Quimica, Universidad 
      Nacional de Colombia, Cra 30 No 45-03 Edificio 451 Lab 201-1, Bogota, Colombia.
FAU - Reyes-Montano, Edgar A
AU  - Reyes-Montano EA
AD  - Grupo de Investigacion en Proteinas, Departamento de Quimica, Universidad 
      Nacional de Colombia, Cra 30 No 45-03 Edificio 451 Lab 201-1, Bogota, Colombia.
FAU - Recio-Pinto, Esperanza
AU  - Recio-Pinto E
AD  - Department of Anesthesiology, Perioperative Care and Pain Medicine, NYU Langone 
      Medical Center, 180 Varick Street, Room 677, New York, NY, 10014, USA. 
      Recioe02@nyu.edu.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170516
PL  - England
TA  - BMC Neurosci
JT  - BMC neuroscience
JID - 100966986
RN  - 0 (Conotoxins)
RN  - 0 (EAR16 peptide)
RN  - 0 (EAR18 peptide)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Peptides)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 93438-65-4 (conotoxin GV)
SB  - IM
MH  - Animals
MH  - Conotoxins/pharmacology
MH  - Excitatory Amino Acid Antagonists/chemical synthesis/*pharmacology
MH  - HEK293 Cells
MH  - Hippocampus/drug effects
MH  - Humans
MH  - Molecular Docking Simulation
MH  - Neurons/*drug effects
MH  - Peptides/chemical synthesis/*pharmacology
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors
PMC - PMC5433008
OTO - NOTNLM
OT  - Conantokin-G
OT  - GluN2A
OT  - GluN2B
OT  - Hippocampal neurons
OT  - NMDA
EDAT- 2017/05/18 06:00
MHDA- 2018/01/11 06:00
PMCR- 2017/05/16
CRDT- 2017/05/18 06:00
PHST- 2016/10/21 00:00 [received]
PHST- 2017/05/04 00:00 [accepted]
PHST- 2017/05/18 06:00 [entrez]
PHST- 2017/05/18 06:00 [pubmed]
PHST- 2018/01/11 06:00 [medline]
PHST- 2017/05/16 00:00 [pmc-release]
AID - 10.1186/s12868-017-0361-4 [pii]
AID - 361 [pii]
AID - 10.1186/s12868-017-0361-4 [doi]
PST - epublish
SO  - BMC Neurosci. 2017 May 16;18(1):44. doi: 10.1186/s12868-017-0361-4.