VIP (vasoactive intestinal peptide)

Vasoactive intestinal peptide (VIP) is a 28-amino-acid neuropeptide of the secretin-glucagon family that acts on VPAC1 and VPAC2 receptors. It regulates smooth muscle, secretion and immune function, and synthetic VIP (aviptadil) has been studied clinically.

Last reviewed 2026-10-25 by the PeptideWiki editorial team. Editorial policy.

Overview

Vasoactive intestinal peptide was isolated around 1970 from porcine intestine on the basis of its ability to dilate blood vessels. It is now known as a widely distributed neuropeptide, found in neurons of the central and peripheral nervous systems, including the gut, airways, genitourinary tract and immune organs. It belongs to the same family as secretin, glucagon and pituitary adenylate cyclase-activating polypeptide (PACAP).

VIP has many physiological roles, including smooth muscle relaxation, stimulation of intestinal water and electrolyte secretion, vasodilation and regulation of immune responses. Tumors that secrete excess VIP cause a characteristic syndrome of severe watery diarrhea, illustrating its secretory effects. Synthetic VIP, called aviptadil, has been studied in clinical trials, including in respiratory failure, and VIP signaling is also a research target in immunology and circadian biology.

Structure

VIP is a linear 28-residue peptide with a C-terminal amide, beginning His-Ser-Asp-Ala-Val-Phe-Thr-Asp and ending with Asn-Ser-Ile-Leu-Asn-NH2. Its sequence is highly conserved among mammals. It is processed from a larger precursor, prepro-VIP, which also contains the related peptide PHM (peptide histidine methionine) in humans. VIP is largely disordered in water and forms a helical structure in membrane-like environments and when bound to its receptors. It contains a methionine at position 17, which is susceptible to oxidation, and is rapidly degraded by peptidases in biological fluids.

Mechanism

VIP acts mainly through two class B G-protein-coupled receptors, VPAC1 and VPAC2, which it shares with PACAP; PACAP additionally acts on the PAC1 receptor, for which VIP has lower affinity. VPAC receptor activation typically couples to Gs and increases intracellular cAMP, producing smooth muscle relaxation, epithelial secretion and other effects.

In the immune system, VIP is produced by neurons and some immune cells and has been described in cell and animal studies as generally anti-inflammatory, reducing pro-inflammatory cytokines and influencing T-cell differentiation and macrophage activity. In the brain, VIP neurons of the suprachiasmatic nucleus are important for synchronizing the circadian clock.

Research

Respiratory research

VIP is abundant in the lungs, where it relaxes airway and vascular smooth muscle and has been studied for effects on inflammation. Aviptadil has been investigated in pulmonary hypertension, sarcoidosis and acute respiratory distress, including clinical trials in critically ill patients with COVID-19 respiratory failure. Those trials did not lead to FDA approval, and efficacy in respiratory failure has not been established.

Immune regulation

Cell and rodent studies have described VIP as an immunomodulatory neuropeptide, with reported effects in models of arthritis, colitis, sepsis and autoimmune inflammation. The short half-life of native VIP in circulation has led to research on stabilized analogues, receptor-selective agonists and delivery systems. These findings remain largely preclinical. Human evidence for immune effects of administered VIP is limited, and translating these findings would require addressing its rapid degradation and broad receptor distribution.

Gastrointestinal physiology

VIP is a key enteric neurotransmitter regulating intestinal secretion, motility and blood flow. VIP-secreting tumors, called VIPomas, produce profuse watery diarrhea and low blood potassium, which demonstrates the peptide's effects in humans. Somatostatin analogues are used clinically to manage this syndrome, which is an example of targeting VIP physiology rather than giving VIP. VIP is also studied in enteric neuron research.

Circadian and neuroscience research

In the suprachiasmatic nucleus, VIP and the VPAC2 receptor are required for normal synchronization of circadian rhythms in rodents, and mice lacking either show disrupted rhythms. VIP is also studied in cortical interneuron circuits, where VIP-expressing neurons are a well-defined cell class. This work is mechanistic and uses animal models. These studies concern endogenous VIP signaling, not administration of the peptide.

Regulatory status

VIP (aviptadil) is not approved by the FDA as a standalone drug for any use. Aviptadil has been studied in clinical trials, including in respiratory failure, without resulting in FDA approval. Status outside the US varies, including for combination products, so current national labeling should be checked. Its compounding status should be checked against current FDA lists. For sport, check the current WADA Prohibited List.

Status changes often. See the regulatory tracker for dated updates.

Quality and identity testing

A good certificate of analysis should confirm identity by mass spectrometry, with the observed mass matching the expected mass shown on this page for the C-terminally amidated sequence, and report HPLC purity with the chromatogram. Check for the C-terminal amide, since a free acid differs by about 1 Da. Methionine 17 oxidation gives a +16 Da species that should be looked for and reported. Asparagine and aspartate residues can deamidate or isomerize, producing closely eluting impurities. As a 28-residue synthetic peptide, deletion sequences are also possible. The salt form and net peptide content should be stated, and endotoxin results matter for cell and immune work.

Open VIP (vasoactive intestinal peptide) in the sequence analyzer to see the expected [M+H]⁺ and multiply charged ions for an MS identity check (set the N-acetyl, amide and disulfide options to match).

For a walkthrough of each section of a certificate, see how to read a COA.

Storage and stability

Store lyophilized VIP sealed at -20 °C or colder, protected from light, moisture and air, and equilibrate before opening. The methionine residue is oxidation-prone, so minimize air exposure and consider inert-gas purging for long-term storage. VIP adsorbs to surfaces and degrades quickly in biological matrices, so low-binding tubes and protease inhibitors may be useful in experiments. Aliquot solutions for frozen storage at -20 °C or below and avoid repeated freeze-thaw cycles.

Download the VIP (vasoactive intestinal peptide) data sheet (PDF): sequence, masses, expected MS ions and handling on one printable page.

Latest research

Frequently asked questions

Related compounds

• LL-37

  LL-37 is the 37-amino-acid antimicrobial peptide released from human cathelicidin hCAP18. It is studied for direct antimicrobial activity and immune-modulating effects in cell, animal and early human studies, and is not approved for any use.

• Thymosin α1

  Thymosin α1 is a 28-amino-acid N-acetylated peptide derived from prothymosin α. Its synthetic form, thymalfasin (Zadaxin), is approved in several countries outside the US and has been studied as an immune modulator in clinical trials.

• Oxytocin

  Oxytocin is a nine-amino-acid peptide hormone made in the hypothalamus and released from the posterior pituitary, with a disulfide-bridged ring structure. It regulates uterine contraction and milk ejection, and synthetic oxytocin (Pitocin) is FDA-approved.

• KPV

  KPV is the tripeptide lysine-proline-valine, the C-terminal sequence of alpha-melanocyte-stimulating hormone. It is studied for anti-inflammatory effects in cell and rodent models, particularly of intestinal inflammation, and is not approved for any use.

References

1. PubMed: all indexed literature on VIP (vasoactive intestinal peptide)
2. ClinicalTrials.gov: registered studies mentioning VIP (vasoactive intestinal peptide)