RFamide-Related Peptide-1

Novel Neuropeptide with the carboxyl C-terminal Arg-Phe-NH2!

Among peptides with the carboxyl (C)-terminal Arg-Phe-NH2 (RFamide family of peptides), FMRF-Amide (code 4142-v) was first isolated from Mollusks in 1977 [Science, 197, 670 (1977) ]. Another member of this family, Leu-Pro-Leu-Arg-Phe-NH2 (code 4144), was identified in chicken brain in 1983, yet there had not been any reports of corresponding mammalian peptides with the same five C-terminal residues. Recently, a new related peptide was deduced from a human database search by elucidating its endogenous form through application of peptide/DNA chemistry. The name of the target peptide is RFamide-related peptide-1 (RFRP-1).




Human RFRP-1 was first predicted to be a 12 amino acid residue peptide. Subsequent synthesis and biochemical studies found it to be a ligand for the orphan receptor, OT7T022 (also called FF1)[Nat. Cell Biol., 2, 703 (2000) ]. Later, the endogenous form of human RFRP-1 was determined to be composed of 37 amino acid residues including the above 12-residue peptide at its C-terminus[Biochim. Biophys. Acta., 1540, 221 (2001) ]. The same peptide was isolated by another group who named it NPSF(1-37)[J. Biol. Chem., 276, 36961 (2001) ]. Human RFRP-1 inhibits forskolin-stimulated cAMP production in CHO cells expressing OT7T022 (ED50=21 nM). The potency is slightly less than that of the 12-residue peptide (ED50=4.9 nM), however, this result suggests that the C-terminal portion of RFRP-1 is responsible for the recognition of OT7T022. Immunoreactive RFRP-1 was observed in the central nervous system (CNS), with the highest amount detected in the hypothalamus. Specific receptors of RFRP-1, OT7T022 or FF1, have been found in the CNS. It is interesting to note that the synthetic peptide composed of 12 amino acid residues described above has shown prolactin-releasing activity at 10 nM [Nat. Cell Biol., 2, 703 (2000) ] and that rat NPSF(1-37) has the anti-opioid effect in two models of nociception at 1.0 nmol/rat [J. Biol. Chem., 276, 36961 (2001) ].

This new synthetic product RFRP-1 should serve as an important biochemical tool to further research investigations.