title: Neuropeptide FF analog RF9 is not an antagonist of NPFF receptor and decreases food intake in mice after its central and peripheral administration.
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 [Tyr(1)]NPFF. In vivo experiments with fasted mice confirmed that centrally injected [Tyr(1)]NPFF significantly lowered food intake. However, RF9, a putative NPFF2 antagonist, did not reverse the anorectic effect of [Tyr(1)]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.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic.
authors.forename: Lenka
authors.initials: L
authors.lastname: Maletínská
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic.
authors.forename: Anežka
authors.initials: A
authors.lastname: Tichá
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic.
authors.forename: Veronika
authors.initials: V
authors.lastname: Nagelová
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic.
authors.forename: Andrea
authors.initials: A
authors.lastname: Spolcová
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic.
authors.forename: Miroslava
authors.initials: M
authors.lastname: Blechová
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Elbert
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic. Electronic address: zelezna@uochb.cas.cz.
authors.forename: Blanka
authors.initials: B
authors.lastname: Zelezná
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D001667:Binding, Competitive; D016466:CHO Cells; D045744:Cell Line, Tumor; D003412:Cricetulus; D004151:Dipeptides / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D006801:Humans; D008297:Male; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D018013:Receptors, Neuropeptide / Q000378:metabolism*
chemical_list: D001067:Appetite Depressants; D004151:Dipeptides; D009842:Oligopeptides; D018013:Receptors, Neuropeptide; C508361:adamantylcarbonyl-arginyl-phenylalaninamide; C083929:neuropeptide FF receptor; C105455:neuropeptide FF, Tyr(1)-N-methyl-Phe(3)-; D048049:Extracellular Signal-Regulated MAP Kinases; D000218:Adamantane