VIP — vasoactive intestinal peptide — is a 28-residue, C-terminally amidated neuropeptide of the secretin-glucagon superfamily that signals through the VPAC1 and VPAC2 G protein-coupled receptors to raise intracellular cyclic AMP. First isolated from porcine intestine in the early 1970s on the strength of its vasodilatory activity, it turned out to be distributed far beyond the gut: through the central and peripheral nervous systems, the airways, the gastrointestinal tract and immune tissue. That breadth is why a single molecule appears in literatures as different as circadian biology, airway physiology and immune regulation.
This page covers the origin and structure of VIP, its receptor pharmacology, the research areas in which it is studied, and the practical laboratory detail — sizes, reconstitution arithmetic, stability and certificate interpretation. VIP is supplied as a lyophilized powder for laboratory research use only.
VIP at a glance
| Property | Value |
|---|---|
| Full name | Vasoactive intestinal peptide (vasoactive intestinal polypeptide) |
| Sequence | HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH2 |
| Length | 28 residues, C-terminally amidated |
| Superfamily | Secretin-glucagon (with PACAP, secretin, glucagon, GHRH) |
| CAS number | 37221-79-7 |
| Molecular weight | 3326.80 g/mol |
| Receptors | VPAC1, VPAC2 (class B GPCRs); PAC1 with much lower affinity |
| Primary second messenger | Cyclic AMP via Gs and adenylyl cyclase |
| Physical form | Lyophilized powder, sealed glass vial |
| Sizes supplied | 5 mg, 10 mg |
| Purity specification | ≥99% by RP-HPLC with mass confirmation |
Origin and structure
VIP was isolated by Said and Mutt from porcine duodenum during a systematic search for intestinal vasoactive substances, and its name records that history rather than its biology — the molecule is not primarily an intestinal hormone. It is encoded by the VIP gene, whose precursor also yields the related peptide PHM (PHI in some species), and it is synthesised in neurons rather than in a classical endocrine gland, functioning as a neurotransmitter and paracrine mediator.
Two structural features define it. The first is family membership: VIP shares substantial sequence identity with PACAP, secretin, glucagon and growth hormone-releasing hormone, all of which adopt a comparable helical fold and all of which engage class B G protein-coupled receptors through a two-domain mechanism — the C-terminal half of the peptide binds the large extracellular domain of the receptor, and the N-terminal residues then engage the transmembrane core to trigger signalling. This division has a direct experimental consequence: N-terminally truncated fragments retain binding but lose activation, which is how antagonists in this family are constructed.
The second feature is C-terminal amidation. The native peptide terminates in an asparagine amide rather than a free carboxylate, a post-translational modification generated by peptidylglycine alpha-amidating monooxygenase. Amidation removes the terminal negative charge and is required for full receptor engagement; a free-acid version of the same sequence is a materially different molecule. Any laboratory ordering VIP should confirm that the amide is present, because this is a real and consequential distinction between products.
How VIP is thought to work
VIP binds VPAC1 and VPAC2 with roughly comparable affinity, and both couple predominantly to Gs. Receptor occupancy activates adenylyl cyclase, raises cyclic AMP and activates protein kinase A, with downstream CREB-mediated transcriptional changes. Additional coupling to phospholipase C has been reported in some systems, and both receptors also show beta-arrestin recruitment and internalisation.
Because VPAC1 and VPAC2 have different tissue distributions — VPAC1 more prominent in lung, liver and lymphocytes, VPAC2 in smooth muscle, the suprachiasmatic nucleus and pancreatic islets among others — the same ligand produces very different tissue-level readouts. This is the reason a great deal of VIP research uses selective analogues rather than the native peptide: to attribute an effect to one receptor subtype rather than the pair.
Three consequences of cyclic AMP elevation account for most of the reported physiology. In smooth muscle, protein kinase A activity reduces contractile tone, which is the basis of the vasodilation and airway relaxation observed in the original studies. In immune cells, elevated cyclic AMP is broadly associated in the literature with reduced pro-inflammatory cytokine production and shifts in T-cell phenotype. In neurons of the suprachiasmatic nucleus, VPAC2 signalling is reported to be central to synchronising the circadian pacemaker — mice lacking VPAC2 show markedly disrupted circadian rhythmicity.
One property matters enormously in practice: native VIP is short-lived. It is a substrate for dipeptidyl peptidase-4 and other peptidases, with a plasma half-life reported in minutes. A very large applied literature exists purely on stabilised analogues and delivery systems, and any experiment using the native sequence in a system containing active proteases must account for this.
What research has examined
Immune modulation and inflammation
VIP appears extensively in work on macrophage and dendritic cell phenotype, regulatory T-cell induction and cytokine profiles, and in rodent models of autoimmune and inflammatory disease. This is the strand that places it alongside KPV and LL-37 in inflammation-directed catalogues, though the mechanisms are unrelated: a class B GPCR agonist, an intracellular NF-kappa B modulator and a membrane-active host-defence peptide respectively.
Gastrointestinal physiology
As a principal transmitter of enteric inhibitory motor neurons, VIP is studied in smooth muscle relaxation, sphincter behaviour, secretion and barrier biology. Researchers examining epithelial barrier questions often pair it with larazotide acetate, which acts on tight junctions directly rather than through receptor signalling.
Airway and pulmonary research
Bronchodilation, pulmonary vascular tone and pulmonary hypertension models form a distinct body of work, some of it extending to clinical investigation of VIP analogues rather than the native peptide.
Circadian and neuroscience research
VIP-expressing neurons of the suprachiasmatic nucleus are a major topic in chronobiology, with VPAC2 signalling implicated in coupling between pacemaker cells. Separately, VIP appears in neuroprotection and neurodevelopment studies.
Receptor pharmacology
Native VIP is routinely used as the reference agonist in VPAC1 and VPAC2 binding and cyclic AMP accumulation assays — arguably its most common laboratory role, and one that depends entirely on the material being correctly amidated and of verified purity.
All of the above is preclinical and in-vitro work. Native VIP has no marketing authorisation, and clinical investigation in this space has concerned analogues and formulations rather than research-grade peptide.
Forms and sizes we supply
VIP is stocked as a lyophilized powder in 5 mg (USD 115) and 10 mg (USD 200) sealed vials. At 3326.80 g/mol, a 5 mg vial contains approximately 1.5 micromoles. Since receptor assays typically operate in the nanomolar range, that quantity supports a great deal of pharmacology; formulation and animal work consumes it far faster. Related material is grouped under anti-inflammatory peptides, and purchasing checks are set out in our VIP buying guide.
Reconstitution and storage in a laboratory context
The arithmetic: a 5 mg vial reconstituted with 1 mL of diluent gives 5 mg/mL, equivalently 5,000 mcg/mL, or approximately 1.50 mM. A 1:1,000 dilution of that stock gives 1.5 micromolar, and a further 1:100 gives 15 nanomolar — the sort of serial dilution a VPAC binding assay actually requires. Working out the molarity explicitly, rather than reasoning in micrograms, avoids the single most common arithmetic error in receptor work.
VIP is moderately hydrophobic in its central region and benefits from gentle handling: add diluent slowly down the vial wall, swirl rather than shake, and allow the cake to dissolve without vortexing. Adsorption to plasticware is significant at low concentrations, so low-binding tubes and, where appropriate, carrier protein in the assay buffer are standard practice. The methionine at position 17 is an oxidation-sensitive residue, which is a practical argument for protecting stock solutions from air and light. Lyophilized vials are stored at −20 °C or colder and protected from moisture; reconstituted material is aliquoted and refrigerated or frozen so that repeated warming is avoided. Full guidance is in the peptide storage guide.
Purity, COA and how to read one
Each lot is purified by reversed-phase HPLC to at least 99% with mass confirmation and a lot-matched certificate. Two checks are specific to this peptide. First, verify the amide: the observed mass should correspond to 3326.80 g/mol for the amidated peptide, and a value about 1 Da higher indicates the free acid. This is the single most important identity check for VIP and it is read directly from the mass spectrum. Second, look for oxidation. A methionine-containing peptide can show a +16 Da satellite in the mass spectrum and an early-eluting shoulder on the chromatogram, both signs of oxidative degradation during synthesis or storage. Beyond that, standard practice applies — read the chromatogram rather than the headline number, and check net peptide content against gross vial weight. Our COA reading guide covers both in detail.
Regulatory status
VIP is an endogenous human peptide, but the synthetic material supplied here is not an approved medicine, a dietary supplement or a generally available compounded preparation. It is research use only, intended for in-vitro and preclinical laboratory investigation by qualified researchers, and is not for human or veterinary administration. Published physiological findings describe the endogenous peptide and investigational analogues; they are not claims for research-grade material.
Related peptides and further reading
Within the secretin-glucagon superfamily, this catalogue also carries GHRH analogues such as sermorelin and tesamorelin, which share the same structural fold and class B receptor mechanism while acting on an entirely different receptor. For gut-directed context see the gut health research overview; the institutional listings group related material under the VIP family page.