Inflammation Research
Investigational
VIP
Also known as: Vasoactive Intestinal Peptide, vasoactive intestinal polypeptide
28-amino acid regulatory peptide. Studied in circadian-rhythm and immune-signalling research.
Research overview
Vasoactive intestinal peptide (VIP) is a 28-amino-acid peptide first isolated from pig intestine in 1970. It is found in nerves of the gut and in the brain, and belongs to the same family as secretin, glucagon and PACAP. It is cut from a larger precursor protein that also yields PHM-27, a separate 27-amino-acid peptide, so PHM-27 is a related molecule, not another name for VIP (Itoh et al., Nature 1983). VIP acts on two receptors, VPAC1 and VPAC2. Animal studies link it to widening of blood vessels, gut secretion, immune signalling and the body clock; mice lacking VPAC2 could not keep normal day-night rhythms (Harmar et al., 2002).
A synthetic form, aviptadil, was tested in COVID-19 respiratory failure. A 196-patient US trial missed its main endpoint, and a larger NIH-funded trial of about 460 patients was stopped early for futility, with no difference from placebo in recovery or deaths at 90 days (Brown et al., 2023). A smaller 80-patient trial reported shorter hospital stays, a result not yet repeated. Claims about VIP in chronic inflammatory response syndrome (CIRS) rest on uncontrolled reports; no controlled trials have been published. Supplied for laboratory research use only.
Mechanism of action
VIP binds two G-protein coupled receptors, VPAC1 and VPAC2, which also respond to the related peptide PACAP. These receptors signal mainly through Gs proteins, which switch on adenylate cyclase and raise cyclic AMP (cAMP), a messenger molecule inside the cell. In smooth muscle this leads to relaxation and widening of blood vessels, and in cell and animal studies it shifts the balance of inflammatory signals from immune cells. In the brain's master clock, the suprachiasmatic nucleus, VPAC2 signalling is needed for normal day-night rhythms in mice.