The Application of the Neuroprotective and Potential Antioxidant Effect of Ergotamine Mediated by Targeting N-Methyl-D-Aspartate Receptors
(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...
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| Format: | Article |
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MDPI AG
2022-07-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/8/1471 |
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| author | Shinhui Lee Sanung Eom Khoa V. A. Nguyen Jiwon Lee Youngseo Park Hye Duck Yeom Junho H. Lee |
| author_facet | Shinhui Lee Sanung Eom Khoa V. A. Nguyen Jiwon Lee Youngseo Park Hye Duck Yeom Junho H. Lee |
| author_sort | Shinhui Lee |
| collection | DOAJ |
| description | (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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup> influx, which prevents neuronal death. |
| first_indexed | 2024-03-09T10:02:22Z |
| format | Article |
| id | doaj.art-4c91b517e51742169cbafc2cfa3e2304 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-09T10:02:22Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-4c91b517e51742169cbafc2cfa3e23042023-12-01T23:20:00ZengMDPI AGAntioxidants2076-39212022-07-01118147110.3390/antiox11081471The Application of the Neuroprotective and Potential Antioxidant Effect of Ergotamine Mediated by Targeting N-Methyl-D-Aspartate ReceptorsShinhui Lee0Sanung Eom1Khoa V. A. Nguyen2Jiwon Lee3Youngseo Park4Hye Duck Yeom5Junho H. Lee6Department of Biotechnology, Chonnam National University, Gwangju 61186, KoreaDepartment of Biotechnology, Chonnam National University, Gwangju 61186, KoreaDepartment of Biotechnology, Chonnam National University, Gwangju 61186, KoreaDepartment of Biotechnology, Chonnam National University, Gwangju 61186, KoreaDepartment of Biotechnology, Chonnam National University, Gwangju 61186, KoreaGoPath Laboratories, Buffalo Grove, IL 60089, USADepartment of Biotechnology, Chonnam National University, Gwangju 61186, Korea(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 Ca<sup>2+</sup> 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 Ca<sup>2+</sup> influx, which prevents neuronal death.https://www.mdpi.com/2076-3921/11/8/1471NMDAN-methyl-D-aspartateergotamineergot alkaloidantioxidantneuronal disease |
| spellingShingle | Shinhui Lee Sanung Eom Khoa V. A. Nguyen Jiwon Lee Youngseo Park Hye Duck Yeom Junho H. Lee The Application of the Neuroprotective and Potential Antioxidant Effect of Ergotamine Mediated by Targeting N-Methyl-D-Aspartate Receptors Antioxidants NMDA N-methyl-D-aspartate ergotamine ergot alkaloid antioxidant neuronal disease |
| title | The Application of the Neuroprotective and Potential Antioxidant Effect of Ergotamine Mediated by Targeting N-Methyl-D-Aspartate Receptors |
| title_full | The Application of the Neuroprotective and Potential Antioxidant Effect of Ergotamine Mediated by Targeting N-Methyl-D-Aspartate Receptors |
| title_fullStr | The Application of the Neuroprotective and Potential Antioxidant Effect of Ergotamine Mediated by Targeting N-Methyl-D-Aspartate Receptors |
| title_full_unstemmed | The Application of the Neuroprotective and Potential Antioxidant Effect of Ergotamine Mediated by Targeting N-Methyl-D-Aspartate Receptors |
| title_short | The Application of the Neuroprotective and Potential Antioxidant Effect of Ergotamine Mediated by Targeting N-Methyl-D-Aspartate Receptors |
| title_sort | application of the neuroprotective and potential antioxidant effect of ergotamine mediated by targeting n methyl d aspartate receptors |
| topic | NMDA N-methyl-D-aspartate ergotamine ergot alkaloid antioxidant neuronal disease |
| url | https://www.mdpi.com/2076-3921/11/8/1471 |
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