Neuropeptide FF receptors as novel targets for limbic seizure attenuation.

Abstract

Neuropeptide Y (NPY) is a well established anticonvulsant and first-in-class antiepileptic neuropeptide. In this study, the controversial role of NPY1 receptors in epilepsy was reassessed by testing two highly selective NPY1 receptor ligands and a mixed NPY1/NPFF receptor antagonist BIBP3226 in a rat model for limbic seizures. While BIBP3226 significantly attenuated the pilocarpine-induced seizures, neither of the highly selective NPY1 receptor ligands altered the seizure severity. Administration of the NPFF1/NPFF2 receptor antagonist RF9 also significantly attenuated limbic seizure activity. To further prove the involvement of NPFF receptors in these seizure-modulating effects, low and high affinity antagonists for the NPFF receptors were tested. We observed that the low affinity ligand failed to exhibit anticonvulsant properties while the two high affinity ligands significantly attenuated the seizures. Continuous NPFF1 receptor agonist administration also inhibited limbic seizures whereas bolus administration of the NPFF1 receptor agonist was without effect. This suggests that continuous agonist perfusion could result in NPFF1 receptor desensitization and mimic NPFF1 receptor antagonist administration. Our data unveil for the first time the involvement of the NPFF system in the management of limbic seizures.

• Authors: Jeanelle Portelli, Alfred Meurs, Frederic Bihel, Hassan Hammoud, Martine Schmitt, Joery De Kock, Valerie Utard, Jean-Paul Humbert, Isabelle Bertin, Ine Buffel, Jessica Coppens, Dirk Tourwe, Veronique Maes, An De Prins, Tamara Vanhaecke, Ann Massie, Ambikaipakan Balasubramaniam, Paul Boon, Jean-Jacques Bourguignon, Frederic Simonin, Ilse Smolders
• Journal: Neuropharmacology (Neuropharmacology) Vol. 95 Pg. 415-23 (Aug 2015) ISSN: 1873-7064 [Electronic] England
• PMID: 25963417 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Anticonvulsants
• BIBP 3226
• Dipeptides
• Receptors, Neuropeptide
• Receptors, Neuropeptide Y
• adamantylcarbonyl-arginyl-phenylalaninamide
• neuropeptide FF receptor
• neuropeptide Y-Y1 receptor
• Pilocarpine
• Arginine
• Adamantane

Topics

• Adamantane (analogs & derivatives, pharmacology)
• Animals
• Anticonvulsants (pharmacology)
• Arginine (analogs & derivatives, pharmacology)
• CHO Cells
• Cricetulus
• Dipeptides (pharmacology)
• Disease Models, Animal
• HEK293 Cells
• Humans
• Limbic System (drug effects, metabolism)
• Male
• Pilocarpine
• Rats, Wistar
• Receptors, Neuropeptide (agonists, antagonists & inhibitors, genetics, metabolism)
• Receptors, Neuropeptide Y (antagonists & inhibitors, genetics, metabolism)
• Seizures (drug therapy, metabolism)