RFamide-related peptide-3 (RFRP-3)

Also known as RFRP-3; NPVF-derived RFRP-3

An NPVF-derived RFamide peptide used to investigate NPFFR1 signalling and context-dependent neuroendocrine circuits.

Length: 8 amino acids in the commonly studied short human form; species-dependent
Half-life: Not well characterised
Mechanism: RFRP-3 preferentially activates NPFFR1/GPR147, commonly engaging Gi/o-dependent inhibition of cyclic AMP signalling. Activity at NPFFR2/GPR74 and context-dependent neuronal responses mean that receptor attribution requires appropriate controls.
Studied in: Receptor-transfected cells, hypothalamic slices, pituitary cultures and rodent neuroendocrine models examine RFRP-3 signalling within reproductive-axis and stress-responsive circuits.

About RFamide-related peptide-3 (RFRP-3)

RFRP-3 belongs to the LPXRFamide peptide family and is generated from the precursor encoded by NPVF. The commonly studied short human sequence is VPNLPQRF-NH₂, an eight-residue amidated peptide; rodent RFRP-3 sequences are longer and differ substantially outside the conserved C-terminal region. Mammalian RFRPs were characterised around 2000, alongside work establishing avian gonadotrophin-inhibitory hormone. RFRP-3 is considered a mammalian member of that broader signalling family, but its experimental effects are not uniformly inhibitory.

NPFFR1, historically GPR147, is the principal receptor used to study RFRP-3 pharmacology. In recombinant systems it commonly couples to Gi/o proteins, allowing inhibition of stimulated cyclic AMP accumulation to serve as a functional readout. Hypothalamic and pituitary preparations investigate interactions with gonadotrophin-releasing hormone networks and hormone secretion. Responses depend on species, physiological state and preparation. Accordingly, the label RFRP-3 alone is insufficient to define a reagent without its full sequence, terminal modification and species designation.

Laboratory notes

Require an explicit sequence and species designation: the short human octapeptide must not be treated as sequence-identical to rodent RFRP-3.
Confirm C-terminal amidation and use mass spectrometry or chromatography to assess identity and integrity.
Pair NPFFR1 assays with receptor-negative controls and, where relevant, NPFFR2 counter-screens; document the cyclic AMP stimulation conditions.

Storage and reconstitution basics: storage guide.

Questions about RFamide-related peptide-3 (RFRP-3)

Why is a single universal length not listed?

RFRP-3 sequences and mature peptide lengths differ between species. The commonly studied short human form has eight residues, whereas widely used rodent forms are longer.

Is RFRP-3 identical to avian gonadotrophin-inhibitory hormone?

No. They are related members of the LPXRFamide family, but their sequences and experimental contexts differ.

Does NPFFR1 activation guarantee inhibition in every preparation?

No. Gi/o-linked signalling in a receptor assay does not establish the net response of a multicellular neuronal or endocrine preparation. RFRP-3 is for research use only.

Is RFamide-related peptide-3 (RFRP-3) for human use?

No. It is supplied strictly for in-vitro laboratory research and is not for human or animal consumption.

Related research peptides

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