VIP, or vasoactive intestinal peptide, is a naturally occurring 28-amino-acid neuropeptide that acts on the VPAC1 and VPAC2 receptors and is widely distributed in the nervous system, gut and immune tissues. Laboratory studies use the VIP peptide to examine class B G protein-coupled receptor signalling, cyclic AMP pathways, neuropeptide biology and immune-cell cytokine regulation in cell culture and animal models. Its short half-life and sensitivity to oxidation make the quality and handling of synthetic material especially important. This article summarises its structure, mechanism, published research areas and the analytical and storage standards needed for reproducible work. It is written for laboratory researchers and offers no guidance on human use.
What is VIP?
VIP is classified as a neuropeptide and a member of the secretin, glucagon and growth hormone-releasing hormone peptide family, a group of structurally related hormones that act on class B receptors. Its sequence is His-Ser-Asp-Ala-Val-Phe-Thr-Asp-Asn-Tyr-Thr-Arg-Leu-Arg-Lys-Gln-Met-Ala-Val-Lys-Lys-Tyr-Leu-Asn-Ser-Ile-Leu-Asn, with an amidated C-terminus, usually written HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH2. The molecular weight is approximately 3326 Da. The sequence contains a single methionine at position 17, two tyrosines, one phenylalanine and several basic residues, and in solution the peptide adopts a largely helical structure at its C-terminal end when it is bound to its receptors or in a membrane-like environment.
The peptide was isolated in 1970 by Sami Said and Viktor Mutt, who purified it from porcine intestinal tissue after Said had observed vasodilator activity in lung extracts, which is the origin of the name. Mutt and Said went on to determine the sequence in the early 1970s, and the work established that the peptide was structurally related to secretin, which explained several of its overlapping activities. A closely related peptide, pituitary adenylate cyclase-activating polypeptide (PACAP), was characterised later, and the two peptides share receptors, which complicates the interpretation of experiments.
Researchers will meet VIP referred to as “VIP”, “VIP peptide” and “VIP 28”, and a pharmaceutical form of the peptide under the generic name aviptadil is used in some jurisdictions. That product is manufactured and supplied under pharmaceutical standards, and research-grade material is not equivalent to it.
Regulatory context matters for any UK buyer. To the author’s understanding, VIP is not authorised as a medicine in the United Kingdom, and this should be checked against current Medicines and Healthcare products Regulatory Agency (MHRA) records. The MHRA has issued warnings about unlicensed products marketed for human use. The material is relevant here only as a laboratory research reagent.
Mechanism of action
VIP acts on three receptors that belong to class B of the G protein-coupled receptor superfamily. VPAC1 and VPAC2 bind VIP and PACAP with similar, high affinity. A third receptor, PAC1, binds PACAP with high affinity but VIP with much lower affinity. In practice, therefore, VIP is the preferred natural ligand for VPAC1 and VPAC2, and PACAP is the main ligand for PAC1.
Class B receptors are engaged through two sites. The C-terminal portion of the peptide binds the large extracellular domain, which captures the ligand, and the N-terminal region then inserts into the transmembrane core to trigger activation. This is why truncation of the N-terminus can convert an agonist into an antagonist, a principle used to design receptor-selective tools.
Receptor activation stimulates the G protein Gs, which activates adenylyl cyclase and raises intracellular cyclic AMP (cAMP). Protein kinase A is then activated and phosphorylates downstream targets, including the transcription factor CREB. In some cell types the receptors also couple to other pathways, including phospholipase C signalling, so the readout depends on the cell line and its receptor expression.
VPAC1 and VPAC2 differ in distribution. VPAC1 is expressed in the lung, liver, intestine and several immune cell types. VPAC2 is expressed in the brain, including the suprachiasmatic nucleus, in smooth muscle and in some immune cells. Because VIP engages both and PACAP overlaps with it, researchers use receptor-selective agonists and antagonists, knockout models and receptor-expressing cell lines to attribute a response to a single receptor.
In cell-based work, the usual readouts are cAMP accumulation, cAMP-response element reporter assays and downstream gene expression. In these systems, “dosage” means molar concentration in the medium, which depends on net peptide content, adsorption to plasticware and protease activity in any serum used. VIP is cleaved within minutes by peptidases, including dipeptidyl peptidase IV and neutral endopeptidase, so effective concentration can fall during an experiment, and stability in the medium should be checked.
What the research shows
The literature on VIP spans more than five decades, and it covers biochemistry, receptor pharmacology, neuroscience and immunology. Four areas are summarised below in general terms. Readers should consult the primary papers for methods, concentrations and statistics, because commercial summaries often overstate findings.
The first area is the original isolation and sequencing. Said and Mutt reported in 1970 in Science that a peptide purified from intestinal tissue produced vasodilator activity in animal preparations, and the sequence was determined shortly afterwards. These papers established the molecule and its relationship with secretin and glucagon. The foundational work can be located through a PubMed search for the isolation of vasoactive intestinal peptide by Said and Mutt.
The second area is receptor cloning and pharmacology. The VPAC1 and VPAC2 receptors were cloned in the early 1990s, and later work characterised their ligand selectivity, signalling and tissue distribution. The International Union of Basic and Clinical Pharmacology published a review of the receptors for VIP and PACAP by Harmar and colleagues in 2012, which remains a standard reference for nomenclature and pharmacology. It can be explored through a PubMed search for the IUPHAR review of VIP and PACAP receptors.
The third area is immune-cell biology. A body of work from groups led by Mario Delgado and Doina Ganea, among others, examined how VIP affects cytokine production by macrophages and T cells in culture, and how it influences antigen-presenting cell function in mouse models. They reported that VIP changed the production of several cytokines by activated immune cells through VPAC receptors and cAMP signalling. These are cell-culture and rodent findings, described here only as part of the scientific record, and they carry no implication for use in people. The topic can be reached through a PubMed search on VIP and macrophage cytokine regulation.
The fourth area is circadian neuroscience. Neurons in the suprachiasmatic nucleus, the brain’s central clock in mammals, express VIP, and studies of VIP-deficient and VPAC2-deficient mice reported disrupted circadian rhythms and impaired synchronisation among clock neurons. This work established VIP as a signalling molecule in the coordination of circadian timing in rodents and is a good example of how a single peptide can be studied in a very different context.
A recurring limitation runs through this body of work. VIP is cleared quickly, so results depend on delivery method and stability, receptor overlap with PACAP complicates interpretation, and the exact material used is not always characterised analytically. Reproducibility therefore depends on knowing exactly what was in the vial.
Research applications
In the laboratory, the VIP peptide is used in several contexts. The most common is receptor pharmacology, where it serves as a reference agonist at VPAC1 and VPAC2 to characterise signalling, benchmark novel ligands, including more stable analogues, and validate cAMP and reporter assays. It is typically run alongside PACAP and receptor-selective compounds so that each receptor’s contribution can be separated.
A second context is immune-cell culture. VIP is used in cultures of macrophages, dendritic cells and lymphocytes to examine cAMP-dependent regulation of cytokine production and antigen presentation, with receptor antagonists and receptor-deficient cells used to define specificity. Endotoxin control is important here, because immune cells respond strongly to trace lipopolysaccharide.
A third context is neuroscience. VIP is applied to brain slices, neuronal cultures and suprachiasmatic nucleus preparations to study neuropeptide signalling and circadian synchronisation, and in approved animal work in rodents, which requires institutional ethical review and, in the United Kingdom, authorisation under the Animals (Scientific Procedures) Act 1986.
A fourth context is peptide chemistry and analytical science. Because native VIP is rapidly degraded, it is a standard test case for strategies to stabilise peptides, including amino acid substitution, lactam bridging and N-terminal modification, and it is a convenient model for liquid chromatography and mass spectrometry methods for oxidation-prone peptides. Reference material of defined identity and purity supports method development.
Purity, storage and handling
A 28-residue peptide with an amidated C-terminus, a methionine and several basic residues is a moderate challenge for solid-phase synthesis. Across that many coupling steps, small inefficiencies accumulate, and the crude product contains truncated and deletion sequences, racemised products and protecting-group adducts. Aspartate-containing sequences, of which VIP has several, are prone to aspartimide formation, a side reaction that yields isomeric impurities difficult to separate from the target. Reversed-phase high-performance liquid chromatography (HPLC) with UV detection at 214 or 220 nm is the standard purity method, and a main peak of at least 98 per cent is commonly expected for receptor pharmacology work. The tyrosine and phenylalanine residues also absorb near 280 nm, so a second wavelength helps to identify the peptide. A stated purity is meaningful only if the method and chromatogram are available.
HPLC must be paired with mass spectrometry. The expected mass is about 3326 Da. A species 16 Da higher indicates oxidation of the methionine, which is the most common degradation product of VIP, and a species 1 Da higher is typical of deamidation at an asparagine. Because oxidation can arise during storage, the mass spectrum is also a useful check on a vial’s history. A clean peak at the wrong mass is a clean peak of the wrong compound.
A batch-specific certificate of analysis matters because purity and peptide content vary between synthesis runs. It should carry a lot number matching the vial, the HPLC trace or purity value, the observed and theoretical masses, the test date and ideally the salt form, net peptide content and endotoxin result. Lyophilised powders contain counterions and residual water, so the weighed mass is not the mass of peptide, and ignoring this introduces systematic errors into any concentration-response comparison. Peptides purified with trifluoroacetic acid are normally supplied as TFA salts, and the counterion is not biologically neutral at every concentration, which matters in cell assays.
Because methionine oxidation proceeds readily once the peptide is in solution, and because the peptide is cleared quickly in biological media, batch-level verification matters more here than with a more robust sequence. UK laboratories sourcing VIP should expect a batch-specific certificate of analysis that states the mass found, the salt form and an endotoxin result, with lyophilised storage at -20°C, and the same documentation standard applies when weighing any best peptides supplier uk claim, since a supplier’s analytical record rather than its search ranking shows whether the vial matches its stated specification.
Lyophilised VIP is generally stored at -20°C in a sealed container with desiccant, and many laboratories use -80°C for long-term archives. Vials should reach room temperature before opening so that condensation does not form on the cold powder. After reconstitution, stability falls. Standard practice is to dissolve the peptide in sterile, endotoxin-free water or a suitable buffer, divide the solution into single-use aliquots and freeze them to avoid repeated freeze-thaw cycles. Refrigerated storage at 2 to 8°C is sometimes used for solutions consumed within days, but the acceptable period should be validated for the assay concerned, preferably by re-running HPLC and mass spectrometry on stored solution. Degassed buffers can slow methionine oxidation, and neutral to alkaline pH can accelerate deamidation.
The peptide is basic and partly hydrophobic, so it adsorbs readily to glass and many plastics at low concentrations. Low-bind tubes are preferred, and a carrier protein such as 0.1 per cent bovine serum albumin is commonly added to dilute working solutions, provided it does not interfere with the assay. Light sensitivity is a secondary but genuine concern, since the tyrosine, phenylalanine and methionine residues can undergo photo-oxidation, so amber vials or dark storage are advisable.
Labelling is a final indicator of quality. Clear naming, sequence, molecular weight, lot number, salt form and an unambiguous research-only statement suggest a supplier that understands its market, while any wording that implies use in humans is a warning sign and raises regulatory concerns in the United Kingdom.
Frequently asked questions
What is VIP peptide used for in laboratory research?
It is used as a reference agonist at the VPAC1 and VPAC2 receptors in cell-based pharmacology, in immune-cell culture studies of cAMP signalling, in neuroscience preparations and in approved animal work. It is a research reagent and not an authorised medicine in the United Kingdom.
What is the sequence and molecular weight of VIP?
Vasoactive intestinal peptide is a 28-residue C-terminally amidated peptide with the sequence HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH2 and a molecular weight of about 3326 Da. The certificate of analysis should show a mass spectrometry result matching this value.
How should VIP peptide be stored for research?
Keep lyophilised peptide at -20°C, or -80°C for long-term archiving, in a sealed, dry, light-protected container. Allow vials to reach room temperature before opening. After reconstitution, aliquot and freeze the solution to limit freeze-thaw cycles and methionine oxidation.
How can I verify the quality of a VIP batch?
Request a batch-specific certificate showing HPLC purity and a mass spectrometry result near 3326 Da, with the salt form, an endotoxin result and a lot number matching the vial. A mass 16 Da higher suggests oxidation. For critical work, independent testing by an accredited laboratory confirms identity.
VIP is supplied for in-vitro laboratory research only and is not intended for human or veterinary use.
