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Neuropeptide FF receptor ligands act on two peptide receptors that modulate pain and opioid responses. Neuropeptide FF (NPFF) and related peptides end in an Arg-Phe-amide (RFamide) motif. Two G protein-coupled receptors for NPFF, NPFF1 and NPFF2, were identified in 2000. NPFF binds both receptors with nanomolar affinity, slightly more tightly to NPFF2. The system is studied in pain processing, opioid tolerance and hormone regulation. RF9, reported in 2006 as a selective NPFF receptor antagonist, prevented opioid-induced hyperalgesia and tolerance in rodents. The category lists Neuropeptide FF, RFRP-3(human) and Neuropeptide AF (cattle), the NPFF2 activator AC-263093 free base and the antagonists RF9 and DP32.
Synonyms: Neuropeptide VF(124-131)(human)
RFRP-3 (Neuropeptide VF(124-131))(human), a human GnIH peptide homolog, is a potent inhibitor of gonadotropin secretion by inhibiting Ca2+ mobilization. RFRP-3(human) is a NPFF1 receptor agonist, it inhibits forskolin-induced production of cAMP with an IC50 of 0.7 nM.
