KPV (Lys-Pro-Val) vs VIP (Vasoactive Intestinal Peptide)

KPV (Lys-Pro-Val)

KPV is the tripeptide lysine–proline–valine, corresponding to the last three residues of alpha-melanocyte-stimulating hormone (α-MSH). It lacks the His-Phe-Arg-Trp core sequence through which α-MSH activates melanocortin receptors, so its pharmacology cannot be assumed to match that of the parent hormone. Interest in it follows reports that C-terminal fragments of α-MSH alter inflammatory signalling in cell and animal models. Published studies are mainly in cultured epithelial and immune cells and in mouse models of chemically induced colitis. The literature is small, and human data are scarce.

VIP (Vasoactive Intestinal Peptide)

VIP, or vasoactive intestinal peptide, is a 28-residue amidated neuropeptide found in central and peripheral neurons and in the gut wall. It belongs to the secretin–glucagon family and is most closely related to pituitary adenylate cyclase-activating polypeptide (PACAP), with which it shares receptors. First isolated from intestinal tissue and named for its action on blood vessels, it is now studied as a neurotransmitter, a smooth-muscle signal and a messenger between the nervous and immune systems. Most of the literature comes from cell, tissue and animal studies. Synthetic VIP has been examined in small human studies, including in pulmonary conditions, but it is cleared from the circulation within a few minutes, which complicates that work.

How KPV (Lys-Pro-Val) acts

How KPV acts has not been settled. Cell studies have reported that it lowers activation of the transcription factor NF-κB and reduces expression of inflammatory cytokines in intestinal epithelial and immune cell lines. In intestinal epithelial cells, uptake through the di- and tripeptide transporter PepT1 has been reported, which would allow it to act inside the cell rather than at a surface receptor. Whether it also signals through melanocortin receptors such as MC1R is disputed, since reports differ and its sequence lacks the usual receptor-binding motif. The mechanistic work is limited and comes largely from cell and rodent models.

How VIP (Vasoactive Intestinal Peptide) acts

VIP binds two class B G-protein-coupled receptors, VPAC1 and VPAC2, with similar affinity, and binds the PACAP-preferring PAC1 receptor much more weakly. Both VPAC receptors couple mainly to Gs, raising cyclic AMP and activating protein kinase A, although coupling to other G proteins has been described. In immune cell cultures this signalling has been reported to alter cytokine production and T-cell differentiation. In the suprachiasmatic nucleus, mouse studies indicate that VIP acting at VPAC2 helps synchronise the neurons of the circadian clock. In smooth muscle preparations it has been examined as a relaxant signal.

The records side by side

• Type: KPV (Lys-Pro-Val), Tripeptide (alpha-MSH fragment); VIP (Vasoactive Intestinal Peptide), Neuropeptide (vasoactive intestinal peptide)
• Length: KPV (Lys-Pro-Val), not recorded; VIP (Vasoactive Intestinal Peptide), 28 amino acids
• Molecular weight: KPV (Lys-Pro-Val), not recorded; VIP (Vasoactive Intestinal Peptide), 3326.8 g/mol
• Molecular formula: KPV (Lys-Pro-Val), not recorded; VIP (Vasoactive Intestinal Peptide), C147H237N43O43S

Reading a comparison

A comparison places two records side by side; it does not merge them. Each description above is drawn from that compound's own record, and the two were not necessarily characterised by the same methods, at the same time, or to the same level of detail. Before comparing any attribute, it is worth establishing that both records describe the substance you think they describe — names are not identifiers, and two entries sharing a name can differ in salt form, stereochemistry or the convention used to state a mass. Where a figure carries no method beside it, the comparison is between two reported numbers rather than between two measurements.