We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Differential Effects of a Full and Biased Ghrelin Receptor Agonist in a Mouse Kindling Model.
- Authors
Buckinx, An; Van Den Herrewegen, Yana; Pierre, Anouk; Cottone, Eleonora; Ben Haj Salah, Khoubaib; Fehrentz, Jean-Alain; Kooijman, Ron; De Bundel, Dimitri; Smolders, Ilse
- Abstract
The ghrelin system has received substantial recognition as a potential target for novel anti-seizure drugs. Ghrelin receptor (ghrelin-R) signaling is complex, involving Gαq/11, Gαi/o, Gα12/13, 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 Gαq and Gα12 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 Gαq or Gα12 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.
- Subjects
EPILEPSY; GHRELIN receptors; DOPAMINE receptors; ARRESTINS; INJECTIONS
- Publication
International Journal of Molecular Sciences, 2019, Vol 20, Issue 10, p2480
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms20102480