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The Glutathione Metabolite γ-Glutamyl-Glutamate Partially Activates Glutamate NMDA Receptors in Central Neurons With Higher Efficacy for GluN2B-Containing Receptors
Gamma-L-glutamyl-L-glutamate (γ-Glu-Glu) was synthetized and further characterized for its activity on cultured neurons. We observed that γ-Glu-Glu elicited excitatory effects on neurons likely by activating mainly the N-methyl-D-aspartate (NMDA) receptors. These effects were dependent on the integr...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763386/ https://www.ncbi.nlm.nih.gov/pubmed/35046818 http://dx.doi.org/10.3389/fphar.2021.794680 |
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author | Sebih, Fatiha Mokrane, Nawfel Fontanel, Pierre Kayatekin, Mete Kaabeche, Mahira Guiramand, Janique Cohen-Solal, Catherine Cens, Thierry Rousset, Matthieu Charnet, Pierre De Jésus Ferreira, Marie-Céleste Thibaud, Jean-Baptiste Ménard, Claudine Cantel, Sonia Rolland, Valérie Vignes, Michel Roussel, Julien |
author_facet | Sebih, Fatiha Mokrane, Nawfel Fontanel, Pierre Kayatekin, Mete Kaabeche, Mahira Guiramand, Janique Cohen-Solal, Catherine Cens, Thierry Rousset, Matthieu Charnet, Pierre De Jésus Ferreira, Marie-Céleste Thibaud, Jean-Baptiste Ménard, Claudine Cantel, Sonia Rolland, Valérie Vignes, Michel Roussel, Julien |
author_sort | Sebih, Fatiha |
collection | PubMed |
description | Gamma-L-glutamyl-L-glutamate (γ-Glu-Glu) was synthetized and further characterized for its activity on cultured neurons. We observed that γ-Glu-Glu elicited excitatory effects on neurons likely by activating mainly the N-methyl-D-aspartate (NMDA) receptors. These effects were dependent on the integrity of synaptic transmission as they were blocked by tetrodotoxin (TTX). We next evaluated its activity on NMDA receptors by testing it on cells expressing these receptors. We observed that γ-Glu-Glu partially activated NMDA receptors and exhibited better efficacy for NMDA receptors containing the GluN2B subunit. Moreover, at low concentration, γ-Glu-Glu potentiated the responses of glutamate on NMDA receptors. Finally, the endogenous production of γ-Glu-Glu was measured by LC-MS on the extracellular medium of C6 rat astroglioma cells. We found that extracellular γ-Glu-Glu concentration was, to some extent, directly linked to GSH metabolism as γ-Glu-Glu can be a by-product of glutathione (GSH) breakdown after γ-glutamyl transferase action. Therefore, γ-Glu-Glu could exert excitatory effects by activating neuronal NMDA receptors when GSH production is enhanced. |
format | Online Article Text |
id | pubmed-8763386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-87633862022-01-18 The Glutathione Metabolite γ-Glutamyl-Glutamate Partially Activates Glutamate NMDA Receptors in Central Neurons With Higher Efficacy for GluN2B-Containing Receptors Sebih, Fatiha Mokrane, Nawfel Fontanel, Pierre Kayatekin, Mete Kaabeche, Mahira Guiramand, Janique Cohen-Solal, Catherine Cens, Thierry Rousset, Matthieu Charnet, Pierre De Jésus Ferreira, Marie-Céleste Thibaud, Jean-Baptiste Ménard, Claudine Cantel, Sonia Rolland, Valérie Vignes, Michel Roussel, Julien Front Pharmacol Pharmacology Gamma-L-glutamyl-L-glutamate (γ-Glu-Glu) was synthetized and further characterized for its activity on cultured neurons. We observed that γ-Glu-Glu elicited excitatory effects on neurons likely by activating mainly the N-methyl-D-aspartate (NMDA) receptors. These effects were dependent on the integrity of synaptic transmission as they were blocked by tetrodotoxin (TTX). We next evaluated its activity on NMDA receptors by testing it on cells expressing these receptors. We observed that γ-Glu-Glu partially activated NMDA receptors and exhibited better efficacy for NMDA receptors containing the GluN2B subunit. Moreover, at low concentration, γ-Glu-Glu potentiated the responses of glutamate on NMDA receptors. Finally, the endogenous production of γ-Glu-Glu was measured by LC-MS on the extracellular medium of C6 rat astroglioma cells. We found that extracellular γ-Glu-Glu concentration was, to some extent, directly linked to GSH metabolism as γ-Glu-Glu can be a by-product of glutathione (GSH) breakdown after γ-glutamyl transferase action. Therefore, γ-Glu-Glu could exert excitatory effects by activating neuronal NMDA receptors when GSH production is enhanced. Frontiers Media S.A. 2022-01-03 /pmc/articles/PMC8763386/ /pubmed/35046818 http://dx.doi.org/10.3389/fphar.2021.794680 Text en Copyright © 2022 Sebih, Mokrane, Fontanel, Kayatekin, Kaabeche, Guiramand, Cohen-Solal, Cens, Rousset, Charnet, De Jésus Ferreira, Thibaud, Ménard, Cantel, Rolland, Vignes and Roussel. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Sebih, Fatiha Mokrane, Nawfel Fontanel, Pierre Kayatekin, Mete Kaabeche, Mahira Guiramand, Janique Cohen-Solal, Catherine Cens, Thierry Rousset, Matthieu Charnet, Pierre De Jésus Ferreira, Marie-Céleste Thibaud, Jean-Baptiste Ménard, Claudine Cantel, Sonia Rolland, Valérie Vignes, Michel Roussel, Julien The Glutathione Metabolite γ-Glutamyl-Glutamate Partially Activates Glutamate NMDA Receptors in Central Neurons With Higher Efficacy for GluN2B-Containing Receptors |
title | The Glutathione Metabolite γ-Glutamyl-Glutamate Partially Activates Glutamate NMDA Receptors in Central Neurons With Higher Efficacy for GluN2B-Containing Receptors |
title_full | The Glutathione Metabolite γ-Glutamyl-Glutamate Partially Activates Glutamate NMDA Receptors in Central Neurons With Higher Efficacy for GluN2B-Containing Receptors |
title_fullStr | The Glutathione Metabolite γ-Glutamyl-Glutamate Partially Activates Glutamate NMDA Receptors in Central Neurons With Higher Efficacy for GluN2B-Containing Receptors |
title_full_unstemmed | The Glutathione Metabolite γ-Glutamyl-Glutamate Partially Activates Glutamate NMDA Receptors in Central Neurons With Higher Efficacy for GluN2B-Containing Receptors |
title_short | The Glutathione Metabolite γ-Glutamyl-Glutamate Partially Activates Glutamate NMDA Receptors in Central Neurons With Higher Efficacy for GluN2B-Containing Receptors |
title_sort | glutathione metabolite γ-glutamyl-glutamate partially activates glutamate nmda receptors in central neurons with higher efficacy for glun2b-containing receptors |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8763386/ https://www.ncbi.nlm.nih.gov/pubmed/35046818 http://dx.doi.org/10.3389/fphar.2021.794680 |
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