Differential Effects of a Full and Biased Ghrelin Receptor Agonist in a Mouse Kindling Model

An Buckinx, Yana Van Den Herrewegen, Anouk Pierre, Eleonora Cottone, Khoubaib Ben Haj Salah, Jean-Alain Fehrentz, Ron Kooijman, Dimitri De Bundel, Ilse Smolders

Onderzoeksoutput: Article

5 Citaten (Scopus)
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Samenvatting

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.

Originele taal-2English
Artikelnummer2480
Aantal pagina's14
TijdschriftInternational Journal of Molecular Sciences
Volume20
Nummer van het tijdschrift10
DOI's
StatusPublished - 20 mei 2019

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