Open AccessCortistatin‐14 Mediates its Anticonvulsant Effects Via sst 2 and sst 3 but Not Ghrelin Receptors
Author(s) -
Aourz Najat,
Portelli Jeanelle,
Coppens Jessica,
De Bundel Dimitri,
Di Giovanni Giuseppe,
Van Eeckhaut Ann,
Michotte Yvette,
Smolders Ilse
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12259
Subject(s) - ghrelin , anticonvulsant , receptor , somatostatin , antagonist , pharmacology , zonisamide , medicine , pilocarpine , chemistry , receptor antagonist , neuropeptide y receptor , endocrinology , microdialysis , epilepsy , biology , neuropeptide , topiramate , neuroscience , central nervous system
Summary Cortistatin ( CST )‐14, a neuropeptide that is structurally and functionally related to somatostatin‐14 ( SRIF ) binds all five somatostatin receptor subtypes (sst 1 –sst 5 ). Using in vivo microdialysis and telemetry‐based electroencephalographic recordings, we provide the first experimental evidence for anticonvulsive effects of CST ‐14 in a pilocarpine‐induced seizure model in rats and mice and for the involvement of sst 2 and sst 3 receptors in these anticonvulsant actions of CST ‐14. Both receptor subtypes are required for the anticonvulsant effects of CST ‐14 given that co‐perfusion of a selective sst 2 antagonist (cyanamid15486) or a selective sst 3 antagonist ( SST 3‐ ODN ‐8) reversed anticonvulsant effect of CST ‐14, and this, independently of each other. Next, as the ghrelin receptor has been proposed as a target for the biological effects of CST ‐14, we used ghrelin receptor knockout mice and their wild type littermates to study the involvement of this receptor in the anticonvulsive actions of CST ‐14. Our results show a significant decrease in seizure duration in both genotypes when CST ‐14 treated mice were compared with corresponding control animals receiving only pilocarpine. In addition, this CST ‐14‐induced decrease was comparable in both genotypes. We here thus provide the first evidence that ghrelin receptors are not involved in mediating anticonvulsant actions of CST ‐14 in vivo .