title: Cortistatin-14 mediates its anticonvulsant effects via sst2 and sst3 but not ghrelin receptors.
abstract: Cortistatin (CST)-14, a neuropeptide that is structurally and functionally related to somatostatin-14 (SRIF) binds all five somatostatin receptor subtypes (sst1-sst5). 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 sst2 and sst3 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 sst2 antagonist (cyanamid15486) or a selective sst3 antagonist (SST3-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.
authors.affiliation: Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Research Group Experimental Pharmacology, Center for Neurosciences (C4N), Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Najat
authors.initials: N
authors.lastname: Aourz
authors.forename: Jeanelle
authors.initials: J
authors.lastname: Portelli
authors.forename: Jessica
authors.initials: J
authors.lastname: Coppens
authors.forename: Dimitri
authors.initials: D
authors.lastname: De Bundel
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Di Giovanni
authors.forename: Ann
authors.initials: A
authors.lastname: Van Eeckhaut
authors.forename: Yvette
authors.initials: Y
authors.lastname: Michotte
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009479:Neuropeptides / Q000627:therapeutic use*; D010456:Peptides, Cyclic / Q000627:therapeutic use*; D010862:Pilocarpine / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D054440:Receptors, Ghrelin / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000502:physiology*; D017481:Receptors, Somatostatin / Q000037:antagonists & inhibitors / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism
chemical_list: D000927:Anticonvulsants; D009479:Neuropeptides; D010456:Peptides, Cyclic; D054440:Receptors, Ghrelin; D017481:Receptors, Somatostatin; C467796:cortistatin 14; C570769:somatostatin receptor 2, mouse; C103631:somatostatin receptor 3; D010862:Pilocarpine
keywords: Cortistatin; Epilepsy; Ghrelin receptor; Pilocarpine; Somatostatin; sst Receptors