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

作者：Maletinska Lenka; Ticha Anezka; Nagelova Veronika; Spolcova Andrea; Blechova Miroslava; Elbert Tomas; Zelezna Blanka^*

来源：Brain Research, 2013, 1498: 33-40.

DOI：10.1016/j.brainres.2012.12.037

• PrRP
• NPFF
• RF9
• Binding
• MAPK/ERK1/2 phosphorylation
• Food intake

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 RP-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 PyrINPFF. 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.

• 出版日期2013-3-1