Scientific Reference
KPV
Evidence profile: Predominantly preclinical
KPV is the three-residue peptide lysine-proline-valine, identical to the final three residues of alpha-melanocyte-stimulating hormone (alpha-MSH). It does not contain the His-Phe-Arg-Trp core through which alpha-MSH activates melanocortin receptors, so its pharmacology should not be assumed to match the hormone's. Attention to it followed reports that C-terminal fragments of alpha-MSH change inflammatory signalling in cell and animal models. The studies are mostly in cultured epithelial and immune cells and in mouse models of chemically induced colitis. The body of work is small, and human data are scarce.
Mechanism of Action
How KPV acts is not settled. Cell studies report that it lowers activation of the transcription factor NF-kB and reduces expression of inflammatory cytokines in intestinal epithelial and immune cell lines. Uptake into intestinal epithelial cells through the di- and tripeptide transporter PepT1 has been described, which would let it act inside the cell, not at a surface receptor. Whether it also signals through melanocortin receptors such as MC1R is disputed, because reports differ and the sequence lacks the usual receptor-binding motif. Mechanistic work is limited and mostly in cell and rodent models.
Molecular Information
- Type: Tripeptide (alpha-MSH fragment)