VIP (Vasoactive Intestinal Peptide) --- Research Product Overview
**Disclaimer:** This article is provided for educational and research purposes only. [VIP](/catalog/vip) is not approved by the FDA for human use. Nothing in this article constitutes medical advice or a recommendation for self-administration. The published clinical literature on inhaled and intravenous VIP includes investigational studies conducted under appropriate regulatory frameworks; nasal and inhalation routes are the most extensively characterized. Viking Labs sells research-grade material exclusively for in-vitro and laboratory animal research use.
Introduction
Vasoactive Intestinal Peptide (VIP) is a 28-residue endogenous neuropeptide first isolated by Sami Said and Viktor Mutt in the early 1970s from porcine duodenum. It belongs to the secretin-glucagon-PACAP peptide superfamily and is broadly distributed in the central and peripheral nervous systems, the gastrointestinal tract, the respiratory tract, and the immune system. Its physiological roles span vasodilation, smooth-muscle relaxation, exocrine secretion regulation, neuromodulation, and immunoregulation.
VIP signals through two G-protein-coupled receptors --- VPAC1 and VPAC2 --- which it binds with similar high affinity, and it shares these receptors with the closely related peptide PACAP (pituitary adenylate cyclase-activating polypeptide). The current research interest in VIP centers on its anti-inflammatory and immunoregulatory pharmacology, particularly via inhaled and nasal routes, where local lung exposure can be achieved without the very short plasma half-life that limits systemic dosing.
Sequence and Physicochemical Properties
Human VIP has the primary sequence H-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-NH2, with a C-terminal amide and a molecular weight of approximately 3325.8 Da. The peptide adopts a partial alpha-helical conformation in membrane-mimetic environments, particularly across residues 7--28, which is the receptor-binding face of the molecule. Net charge at physiological pH is moderately positive.
VIP is highly water-soluble in mild acidic to neutral buffer but susceptible to oxidation at the methionine-17 residue and to N-terminal degradation by dipeptidyl peptidase IV (DPP-IV). Plasma half-life is on the order of 1--2 minutes after intravenous administration, which is the principal pharmacokinetic limitation driving interest in inhaled, nasal, and modified-release formulations.
Research-grade lyophilized VIP targets HPLC purity of >=98 percent. Mass-spectrometric confirmation should show parent ions consistent with the calculated mass (m/z ~1109.6 M+3H]3+ in ESI). Investigators should verify sequence by MS, purity by RP-HPLC, and review the [Certificate of Analysis for residual TFA, water content, and endotoxin levels.
Mechanism of Action
VIP signals through VPAC1 and VPAC2, both class B G-protein-coupled receptors of the secretin family:
Gs / cAMP / PKA. The dominant signaling output is Gs-mediated activation of adenylyl cyclase, elevating intracellular cAMP and activating protein kinase A. PKA phosphorylates downstream effectors including transcription factors that regulate cytokine balance toward an anti-inflammatory profile (suppression of TNF-alpha, IL-6, IL-12; promotion of IL-10).
Th1/Th17 to Th2/Treg shift. In immune cells, VIP signaling promotes a regulatory phenotype, expanding Foxp3+ regulatory T cells while suppressing pro-inflammatory Th1 and Th17 differentiation. This profile underlies most of VIP's anti-inflammatory pharmacology in autoimmune and granulomatous disease models.
RAMP-modulated VPAC1 signaling. The VPAC1 receptor interacts with receptor activity-modifying protein 2 (RAMP2), which biases signaling toward inositol trisphosphate / calcium pathways alongside the canonical cAMP output.
Smooth-muscle relaxation. In airway and vascular smooth muscle, VPAC2 activation drives relaxation through cAMP-mediated reduction in calcium sensitivity of the contractile apparatus.
Preclinical and Clinical Research Summary
VIP's broad immunoregulatory profile has supported investigation across pulmonary sarcoidosis, asthma, pulmonary arterial hypertension, and inflammatory bowel models. The most cited clinical investigation is Prasse et al. (2010), an open-label phase II study in pulmonary sarcoidosis in which 20 patients received nebulized VIP for four weeks. The investigators reported good tolerability, statistically significant reductions in TNF-alpha production by bronchoalveolar lavage cells, and patient-reported improvements in cough and dyspnea. A small number of subjects experienced nasal hemorrhage during BAL procedures, leading to exclusion of two BAL cell-culture data points.
In rodent models, intratracheal or nasal VIP has reduced airway inflammation in asthma models, attenuated granuloma formation in sarcoidosis models, and produced pulmonary vasodilation in PAH models. Anti-inflammatory effects in DSS- and TNBS-colitis models support its broader role as an immunoregulator.
Common Research Applications
VIP is used in research to:
- Probe VPAC1/VPAC2 receptor pharmacology in transfected cell systems.
- Investigate cAMP-dependent anti-inflammatory signaling in primary immune cells.
- Study airway smooth-muscle relaxation and bronchodilation mechanisms.
- Compare nasal, inhaled, and intravenous pharmacokinetics for short-half-life peptides.
Comparator Peptides and Molecules
VIP's place in the research-tool landscape is best understood by comparison with other peptides in the secretin-glucagon-PACAP superfamily and with small-molecule modulators of the same physiological systems.
VIP vs. PACAP. PACAP (pituitary adenylate cyclase-activating polypeptide) is the closest pharmacological cousin --- a 27- or 38-residue peptide that shares the VPAC1 and VPAC2 receptors with VIP and additionally engages a third receptor (PAC1) for which VIP has minimal affinity. PAC1-selective signaling has been associated with neuronal-specific effects including stress response, neuroprotection, and migraine pathology. The VIP-vs-PACAP distinction is therefore mechanistically important: shared VPAC effects can be probed with either ligand, but PAC1-mediated effects require PACAP. From a research-tools perspective, VIP is preferred when investigators want to isolate VPAC1/VPAC2 pharmacology from PAC1.
VIP vs. secretin and glucagon. The broader secretin-superfamily peptides share the class B GPCR architecture and Gs/cAMP signaling output but operate through distinct receptors with non-overlapping tissue distributions. VIP's ubiquitous distribution (CNS, GI, respiratory, immune) makes it the broadest-utility tool of the family.
VIP vs. PDE inhibitors. Phosphodiesterase inhibitors (theophylline, rolipram, roflumilast) elevate intracellular cAMP downstream of receptor activation. The contrast with VIP is mechanistic: VIP triggers cAMP elevation through receptor-coupled adenylyl cyclase, while PDE inhibitors prevent cAMP degradation. Both produce anti-inflammatory effects in airway and immune cells, but VIP additionally engages biased signaling and Th17/Treg-rebalancing pathways that PDE inhibitors do not access.
VIP vs. inhaled corticosteroids. Standard-of-care anti-inflammatory pulmonary therapy operates through glucocorticoid-receptor-mediated transcriptional repression of pro-inflammatory genes. VIP's mechanism is non-glucocorticoid, which has driven research interest in VIP for indications where corticosteroids have efficacy ceilings or unacceptable side-effect profiles (sarcoidosis, certain asthma phenotypes).
VIP vs. antimicrobial-and-immune peptides. For an alternative anti-inflammatory peptide mechanism, see LL-37 antimicrobial peptide; LL-37 acts on TLR-driven innate immunity and direct bacterial-membrane disruption rather than the cAMP-mediated regulatory-cytokine repolarization VIP drives.
Deeper Preclinical Breakdown
Three studies define the modern VIP research evidence base.
Said and Mutt (1970). The foundational isolation paper. Working at the Karolinska Institute, the investigators applied successive ion-exchange and gel-filtration chromatography to porcine duodenal extracts to isolate a 28-residue peptide with potent vasodilatory activity in canine femoral artery preparations. Edman sequencing established the primary structure, and the peptide was named "vasoactive intestinal peptide" reflecting its tissue source and most prominent pharmacological action. This paper opened the secretin-superfamily characterization that subsequently identified PACAP, glucagon-like peptides, and the VPAC/PAC1 receptors. Limitations: the original isolation predated modern receptor pharmacology and the broader immunoregulatory profile was not anticipated.
Prasse et al. (2010), American Journal of Respiratory and Critical Care Medicine (PMID 20442436). The most-cited modern clinical study of VIP. This open-label phase II investigation enrolled 20 patients with biopsy-confirmed pulmonary sarcoidosis at the University of Freiburg. Subjects received nebulized VIP (100 microg three times daily) for four weeks. Bronchoalveolar lavage cells harvested at baseline and end-of-treatment showed statistically significant reductions in TNF-alpha production by stimulated alveolar macrophages, paralleled by patient-reported improvements in cough, dyspnea, and quality of life on validated scales. Two BAL cell-culture data points were excluded due to nasal hemorrhage during the procedure. The investigators interpreted the results as supporting cAMP-mediated anti-inflammatory rebalancing in lung-resident immune cells. Limitations: open-label design without placebo control, single-center, small sample size, and a four-week duration that precludes inference about disease modification.
Onyuksel et al. (2009 and follow-on). A series of papers from the University of Illinois at Chicago group developing nanomicellar VIP formulations for pulmonary arterial hypertension. The polymer-based nanocarrier extends VIP's pulmonary residence time, stabilizes the peptide against rapid plasma proteolysis, and produces both acute vasodilatory and chronic disease-modifying effects in monocrotaline and hypoxia-induced PAH rat models. The methodology represents the dominant approach to overcoming VIP's short-half-life limitation.
Formulation Considerations
Research-grade VIP is supplied as a lyophilized white-to-off-white powder, typically in 1 mg or 5 mg sealed glass vials under inert atmosphere with desiccant. The 28-residue size and methionine-17 oxidation susceptibility make VIP one of the more handling-sensitive research peptides in the catalog. Lyophilized vials are stable for >=24 months at -20 degrees C; storage under inert nitrogen or argon atmosphere is preferred over standard air-fill, and amber vials are recommended for light protection. Reconstitution in mildly acidic water (0.1 percent acetic acid) at 1--2 mg/mL improves dissolution; the partial alpha-helical conformation forms more readily in slightly acidic solution before dilution into neutral buffer. Methionine sulfoxide is the most common impurity, visible as a separate earlier-eluting peak on RP-HPLC; its presence in fresh material indicates oxidation during synthesis or storage. Other common impurities include des-amide (free C-terminal carboxylate), DPP-IV-truncated des-(1,2)-VIP, and TFA counter-ion residues. See the peptide solubility guide for handling notes specific to oxidation-sensitive peptides.
Research-Context Dosing Ranges
Published preclinical and clinical studies provide research-context dose anchors. In-vitro receptor-binding and cAMP-accumulation studies on VPAC1/VPAC2-transfected cells have used 0.1--100 nM for EC50 determination. Primary immune-cell studies (T cells, macrophages, dendritic cells) typically use 1--100 nM for cytokine-rebalancing readouts. Rodent intratracheal asthma models have used 1--10 microg per animal per dose; murine PAH models with nanomicellar formulations have used 0.5--5 microg/kg/day. The Prasse et al. clinical sarcoidosis study used nebulized 100 microg three times daily; that figure is reported here for research-context anchoring only and is not a recommendation for human use.
Cross-References
For broader context within the Viking Labs research library, see LL-37 antimicrobial peptide for a comparator anti-inflammatory peptide, the antimicrobial peptide resistance review for the broader class, the peptide drug delivery 2026 review for nanomicellar and inhalation-delivery context, and the growth hormone axis overview for adjacent endocrine-peptide research. Handling and analytical protocols are covered in the peptide reconstitution guide and reading an HPLC CoA.
Handling, Reconstitution, and Storage
Lyophilized VIP is stable at -20 degrees C for >=24 months in sealed vials with desiccant. Because of methionine-17 oxidation susceptibility, vials should be stored under inert atmosphere where possible and protected from light. Reconstitution in mildly acidic water (0.1 percent acetic acid) at 1--2 mg/mL improves dissolution; subsequent dilution into PBS or bacteriostatic water is appropriate for working solutions. Aliquot to avoid freeze--thaw cycles. Reconstituted material in bacteriostatic water at refrigerated temperature is typically used within 14 days; for longer-term work, aliquots should be kept frozen.
The published clinical research on VIP overwhelmingly uses inhaled or nasal routes for pulmonary indications, and research-handling notes for animal studies should reflect that route preference --- subcutaneous and intravenous routes face the very short plasma half-life noted above.
Summary
VIP is an endogenous 28-residue peptide whose pharmacology spans vasodilation, smooth-muscle relaxation, exocrine regulation, and broad anti-inflammatory immunomodulation via VPAC1 and VPAC2 receptors. Its short plasma half-life shapes a research literature dominated by inhaled, nasal, and locally delivered formulations. The Prasse et al. (2010) sarcoidosis study remains the best-characterized clinical investigation, and rodent models continue to expand the peptide's documented immunoregulatory repertoire.
*This article is provided for informational and research purposes only. Viking Labs does not sell products intended for human consumption.*