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The Application of the Neuroprotective and Potential Antioxidant Effect of Ergotamine Mediated by Targeting N-Methyl-D-Aspartate Receptors

Authors :
Shinhui Lee
Sanung Eom
Khoa V. A. Nguyen
Jiwon Lee
Youngseo Park
Hye Duck Yeom
Junho H. Lee
Source :
Antioxidants, Vol 11, Iss 8, p 1471 (2022)
Publication Year :
2022
Publisher :
MDPI AG, 2022.

Abstract

(1) Background: The N-methyl-D-aspartate receptors (NMDARs) mediate fast excitatory currents leading to depolarization. Postsynaptic NMDARs are ionotropic glutamate receptors that mediate excitatory glutamate or glycine signaling in the CNS and play a primary role in long-term potentiation, which is a major form of use-dependent synaptic plasticity. The overstimulation of NMDARs mediates excessive Ca2+ influx to postsynaptic neurons and facilitates more production of ROS, which induces neuronal apoptosis. (2) Methods: To confirm the induced inward currents by the coapplication of glutamate and ergotamine on NMDARs, a two-electrode voltage clamp (TEVC) was conducted. The ergotamine-mediated inhibitory effects of NR1a/NR2A subunits were explored among four different kinds of recombinant NMDA subunits. In silico docking modeling was performed to confirm the main binding site of ergotamine. (3) Results: The ergotamine-mediated inhibitory effect on the NR1a/NR2A subunits has concentration-dependent, reversible, and voltage-independent properties. The major binding sites were V169 of the NR1a subunit and N466 of the NR2A subunit. (4) Conclusion: Ergotamine effectively inhibited NR1a/NR2A subunit among the subtypes of NMDAR. This inhibition effect can prevent excessive Ca2+ influx, which prevents neuronal death.

Details

Language :
English
ISSN :
20763921
Volume :
11
Issue :
8
Database :
Directory of Open Access Journals
Journal :
Antioxidants
Publication Type :
Academic Journal
Accession number :
edsdoj.4c91b517e51742169cbafc2cfa3e2304
Document Type :
article
Full Text :
https://doi.org/10.3390/antiox11081471