Neuropeptide FF analog RF9 is not an antagonist of NPFF receptor and decreases food intake in mice after its central and peripheral administration

• Published in: Brain research 2013-03, Vol.1498, p.33-40
• Main Authors: Maletínská, Lenka, Tichá, Anežka, Nagelová, Veronika, Špolcová, Andrea, Blechová, Miroslava, Elbert, Tomáš, Železná, Blanka
• Format: Article
• Language: English
• Subjects: Adamantane - analogs & derivatives; Adamantane - pharmacology; amino acid sequences; Animals; antagonists; Appetite Depressants - pharmacology; Binding; Binding, Competitive; Biological and medical sciences; brain; Cell Line, Tumor; cell membranes; CHO Cells; Cricetulus; Dipeptides - pharmacology; Eating - drug effects; Extracellular Signal-Regulated MAP Kinases - metabolism; Food intake; Fundamental and applied biological sciences. Psychology; Humans; in vivo studies; Male; MAPK/ERK1/2 phosphorylation; mice; Mice, Inbred C57BL; Neurology; NPFF; Oligopeptides - metabolism; peptides; Perception; phosphorylation; Phosphorylation - drug effects; PrRP; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; receptors; Receptors, Neuropeptide - metabolism; RF9; subcutaneous injection
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2012.12.037

Abstract Neuropeptide FF (NPFF) belongs to the RF-amide family of peptides bearing the identical C-terminal amino acid sequence (R-F-NH2 ). In addition to NPFF, prolactin-releasing peptide (PrRP), another RF-amide, binds to NPFF receptors with high affinity. A selective antagonist of PrRP has not yet been identified, but a selective antagonist of NPFF, 1-adamantanecarbonyl-RF-NH2 (RF9), was recently reported to antagonize the hyperalgesic effect of NPFF after central administration to mice. In the present study, RF9 competed with NPFF analog D-Y-L-(N-Me)-F-Q-P-Q-R-F-NH2 (1DMe) in binding to CHO-K1 cell membranes transfected with the human NPFF2 receptor. In rat pituitary RC-4B/C cells, where the expression of the NPFF2 receptor was proved by immunodetection, RF9 did not reverse the phosphorylation of MAPK/ERK1/2 induced by [Tyr1 ]NPFF. In vivo experiments with fasted mice confirmed that centrally injected [Tyr1 ]NPFF significantly lowered food intake. However, RF9, a putative NPFF2 antagonist, did not reverse the anorectic effect of [Tyr1 ]NPFF. Paradoxically, RF9 itself exhibited an anorectic effect in fasted mice not only after intracerebroventricular but also after subcutaneous administration. This finding casts doubt on claims that RF9 is an NPFF antagonist.