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Differential Effects of a Full and Biased Ghrelin Receptor Agonist in a Mouse Kindling Model
The ghrelin system has received substantial recognition as a potential target for novel anti-seizure drugs. Ghrelin receptor (ghrelin-R) signaling is complex, involving Gα(q/11), Gα(i/o), Gα(12/13), and β-arrestin pathways. In this study, we aimed to deepen our understanding regarding signaling path...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567032/ https://www.ncbi.nlm.nih.gov/pubmed/31137460 http://dx.doi.org/10.3390/ijms20102480 |
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author | Buckinx, An Van Den Herrewegen, Yana Pierre, Anouk Cottone, Eleonora Ben Haj Salah, Khoubaib Fehrentz, Jean-Alain Kooijman, Ron De Bundel, Dimitri Smolders, Ilse |
author_facet | Buckinx, An Van Den Herrewegen, Yana Pierre, Anouk Cottone, Eleonora Ben Haj Salah, Khoubaib Fehrentz, Jean-Alain Kooijman, Ron De Bundel, Dimitri Smolders, Ilse |
author_sort | Buckinx, An |
collection | PubMed |
description | The ghrelin system has received substantial recognition as a potential target for novel anti-seizure drugs. Ghrelin receptor (ghrelin-R) signaling is complex, involving Gα(q/11), Gα(i/o), Gα(12/13), and β-arrestin pathways. In this study, we aimed to deepen our understanding regarding signaling pathways downstream the ghrelin-R responsible for mediating anticonvulsive effects in a kindling model. Mice were administered the proconvulsive dopamine 1 receptor-agonist, SKF81297, to gradually induce a kindled state. Prior to every SKF81297 injection, mice were treated with a ghrelin-R full agonist (JMV-1843), a Gα(q) and Gα(12) biased ligand unable to recruit β-arrestin (YIL781), a ghrelin-R antagonist (JMV-2959), or saline. Mice treated with JMV-1843 had fewer and less severe seizures compared to saline-treated controls, while mice treated with YIL781 experienced longer and more severe seizures. JMV-2959 treatment did not lead to differences in seizure severity and number. Altogether, these results indicate that the Gα(q) or Gα(12) signaling pathways are not responsible for mediating JMV-1843′s anticonvulsive effects and suggest a possible involvement of β-arrestin signaling in the anticonvulsive effects mediated by ghrelin-R modulation. |
format | Online Article Text |
id | pubmed-6567032 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-65670322019-06-17 Differential Effects of a Full and Biased Ghrelin Receptor Agonist in a Mouse Kindling Model Buckinx, An Van Den Herrewegen, Yana Pierre, Anouk Cottone, Eleonora Ben Haj Salah, Khoubaib Fehrentz, Jean-Alain Kooijman, Ron De Bundel, Dimitri Smolders, Ilse Int J Mol Sci Article The ghrelin system has received substantial recognition as a potential target for novel anti-seizure drugs. Ghrelin receptor (ghrelin-R) signaling is complex, involving Gα(q/11), Gα(i/o), Gα(12/13), and β-arrestin pathways. In this study, we aimed to deepen our understanding regarding signaling pathways downstream the ghrelin-R responsible for mediating anticonvulsive effects in a kindling model. Mice were administered the proconvulsive dopamine 1 receptor-agonist, SKF81297, to gradually induce a kindled state. Prior to every SKF81297 injection, mice were treated with a ghrelin-R full agonist (JMV-1843), a Gα(q) and Gα(12) biased ligand unable to recruit β-arrestin (YIL781), a ghrelin-R antagonist (JMV-2959), or saline. Mice treated with JMV-1843 had fewer and less severe seizures compared to saline-treated controls, while mice treated with YIL781 experienced longer and more severe seizures. JMV-2959 treatment did not lead to differences in seizure severity and number. Altogether, these results indicate that the Gα(q) or Gα(12) signaling pathways are not responsible for mediating JMV-1843′s anticonvulsive effects and suggest a possible involvement of β-arrestin signaling in the anticonvulsive effects mediated by ghrelin-R modulation. MDPI 2019-05-20 /pmc/articles/PMC6567032/ /pubmed/31137460 http://dx.doi.org/10.3390/ijms20102480 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Buckinx, An Van Den Herrewegen, Yana Pierre, Anouk Cottone, Eleonora Ben Haj Salah, Khoubaib Fehrentz, Jean-Alain Kooijman, Ron De Bundel, Dimitri Smolders, Ilse Differential Effects of a Full and Biased Ghrelin Receptor Agonist in a Mouse Kindling Model |
title | Differential Effects of a Full and Biased Ghrelin Receptor Agonist in a Mouse Kindling Model |
title_full | Differential Effects of a Full and Biased Ghrelin Receptor Agonist in a Mouse Kindling Model |
title_fullStr | Differential Effects of a Full and Biased Ghrelin Receptor Agonist in a Mouse Kindling Model |
title_full_unstemmed | Differential Effects of a Full and Biased Ghrelin Receptor Agonist in a Mouse Kindling Model |
title_short | Differential Effects of a Full and Biased Ghrelin Receptor Agonist in a Mouse Kindling Model |
title_sort | differential effects of a full and biased ghrelin receptor agonist in a mouse kindling model |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6567032/ https://www.ncbi.nlm.nih.gov/pubmed/31137460 http://dx.doi.org/10.3390/ijms20102480 |
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