VIP, vasoactive intestinal peptide, is a 28-residue neuropeptide of the secretin and glucagon family and the reference ligand at the VPAC1 and VPAC2 receptors. First isolated from porcine intestine in 1970, it is now known to be released from neurons throughout the enteric, respiratory and central nervous systems and from several immune cell populations. NuVion supplies VIP as a laboratory chemical for in vitro research use only.
Key facts
| Type | Naturally occurring neuropeptide |
| Amino acid count | 28 |
| Family | Secretin and glucagon peptide family |
| C-terminus | Amidated |
| Molecular formula | C147H238N44O42S |
| Molecular weight | 3326.8 g/mol |
| CAS number | 37221-79-7 |
| Supplied form | Lyophilised powder in a sealed vial |
Structure and chemistry
VIP is a linear 28-residue peptide with a free N-terminal histidine and an amidated C-terminal asparagine. The C-terminal amide is not incidental: removing it, as happens when the sequence is made without amidation, sharply reduces receptor affinity, so the amide is a specification point for any preparation intended for pharmacology. The peptide is strongly basic, with several lysine and arginine residues giving a net positive charge near plus three at neutral pH, and it is highly water-soluble.
In aqueous buffer VIP is largely disordered, but in the presence of membranes or membrane-mimetic solvents it folds into an amphipathic alpha helix through residues 7 to 28, with polar and non-polar residues segregating onto opposite faces of the helix. That induced-fit behaviour is characteristic of the secretin family and underlies the two-domain binding model: the helical C-terminal half engages the receptor’s extracellular domain, and the N-terminal residues, particularly histidine 1, are what activate the transmembrane core.
The sequence is closely related to PACAP, which shares 68 per cent identity with VIP and binds VPAC1 and VPAC2 with comparable affinity while also activating the PAC1 receptor. That overlap is the central experimental complication in the field, and distinguishing VPAC-mediated from PAC1-mediated responses generally requires selective analogues or receptor knockdown. Chemically, VIP contains a methionine that oxidises and asparagine residues that deamidate in solution over time, both visible on RP-HPLC as satellite peaks. With free N-terminal histidine the peptide is a dipeptidyl peptidase 4 substrate, so its half-life in serum-containing medium is short.
Mechanism of action
VPAC1 and VPAC2 are class B G protein-coupled receptors. VIP binds both with nanomolar affinity and couples principally to Gs, raising adenylyl cyclase activity, cyclic AMP and protein kinase A. Downstream, phosphorylated CREB alters transcription of cyclic AMP responsive genes, and in smooth muscle the same pathway lowers intracellular calcium sensitivity, which is the cellular basis of the relaxation response measured in isolated tissue preparations. Coupling to Gq and phospholipase C is also described in some cell backgrounds, and beta-arrestin recruitment gives receptor internalisation that can be followed by imaging or BRET.
The immunological readouts are the other major strand. In macrophage, dendritic cell and T-lymphocyte culture, VIP exposure raises cyclic AMP and shifts the profile of cytokines released into conditioned medium, with reported reductions in tumour necrosis factor alpha, interleukin-6 and interleukin-12 output and increases in interleukin-10, measured by ELISA or multiplex immunoassay. The proposed transcriptional route runs through protein kinase A to reduced NF-kappaB nuclear translocation, which is followed by immunoblot on nuclear fractions or by reporter assay. Separately, VIP-stimulated cyclic AMP in epithelial culture activates the cystic fibrosis transmembrane conductance regulator chloride channel, giving a short-circuit current response in Ussing chamber work on epithelial monolayers, and a nitric oxide synthase-dependent component has been described in some vascular and neuronal preparations.
Research applications
- Cyclic AMP accumulation assays in VPAC1 or VPAC2 expressing cell lines, using VIP as reference agonist.
- Competition binding at VPAC1 and VPAC2 to determine affinity and selectivity for analogues under test.
- Cytokine profiling in macrophage, dendritic cell and T-lymphocyte culture by ELISA or multiplex immunoassay.
- NF-kappaB translocation and reporter assays linking receptor activation to transcriptional output.
- Short-circuit current measurement in Ussing chambers on epithelial monolayers, following CFTR-dependent chloride transport.
- Receptor internalisation and beta-arrestin recruitment assays by imaging or BRET, and paired comparison with PACAP to separate VPAC from PAC1 responses.
VIP sits in NuVion’s Immune Signalling category alongside the other peptides used in cytokine and innate signalling research.
Handling in the laboratory
VIP is supplied lyophilised and is reconstituted with bacteriostatic water added slowly down the side of the vial, then swirled gently until dissolved. It is not vortexed hard, since an amphipathic peptide of this length aggregates at an air-liquid interface. The reconstitution calculator converts vial content and diluent volume into a stock concentration. Being strongly basic, VIP adsorbs readily to glass and to untreated plastic, so low-binding tubes and a carrier protein in working dilutions both make a measurable difference at the nanomolar concentrations used in receptor assays.
Unopened vials are kept sealed, dry and refrigerated as stated on the product documentation. Reconstituted solution is refrigerated and used within the period given there, or aliquoted into single-use volumes and frozen. Methionine oxidation is the slow chemical change over extended storage in solution and appears as an early-eluting satellite peak on RP-HPLC. Because the free N-terminal histidine makes the peptide a dipeptidyl peptidase 4 substrate, experiments in serum-containing medium often include a peptidase inhibitor or a parallel stability measurement so that actual exposure is known.
Testing and supply from NuVion
NuVion’s VIP is manufactured at a GMP-audited facility and independently tested by Janoshik Analytical, with purity determined by RP-HPLC and identity confirmed by mass spectrometry. The Certificate of Analysis for a tested batch is published on the product page and in the COA library. The peptide is supplied lyophilised in sealed vials and dispatched from within Australia.
Related compounds
Other peptides used in cytokine and innate signalling assays include KPV, the C-terminal fragment of alpha-MSH, Thymosin Alpha-1 and LL-37.
Frequently asked questions
What is VIP used for in research?
It is the reference agonist at VPAC1 and VPAC2, used in cyclic AMP accumulation and competition binding assays, in cytokine profiling on immune cell culture, in epithelial ion transport measurement by Ussing chamber, and in receptor internalisation work.
How is VIP distinguished from PACAP?
The two share 68 per cent sequence identity and bind VPAC1 and VPAC2 with comparable affinity, while PACAP also activates PAC1. Separating the responses generally requires receptor-selective analogues, receptor knockdown or expression systems carrying a single receptor subtype.
Is VIP a therapeutic good in Australia?
No. NuVion’s VIP is a laboratory chemical for in vitro research. It is not included in the Australian Register of Therapeutic Goods, has not been assessed by the Therapeutic Goods Administration, and is not for human or veterinary use.
How should VIP be stored?
Lyophilised vials are kept sealed, dry and refrigerated per the product documentation. Reconstituted solution is refrigerated and used within the stated period, or aliquoted into single-use volumes and frozen. Low-binding tubes and a carrier protein limit adsorption at working concentrations.
Research use only. This product is a laboratory chemical supplied for in vitro research. It is not included in the Australian Register of Therapeutic Goods and has not been assessed by the Therapeutic Goods Administration for quality, safety or efficacy. It is not for human or veterinary use, and nothing on this page is a representation about therapeutic use.
