Vasoactive Intestinal Peptide (VIP): The Pleiotropic Neuropeptide in Neuroimmune and Circadian Research

Introduction

Vasoactive intestinal peptide (VIP (PMID: 42722571)) is a 28-amino acid neuropeptide that has steadily emerged as one of the most functionally diverse signaling molecules in biomedical research. First isolated from porcine duodenum by Said and Mutt in 1970 and originally characterized for its potent vasodilatory properties, VIP has since been recognized as a pleiotropic mediator with critical roles spanning neuroscience, immunology, circadian biology, and cardiopulmonary physiology ([Said & Mutt, 1970]()).

For dosing, reconstitution, and protocol details, see our VIP (Vasoactive Intestinal Peptide) Dosage Protocol Guide: Neuroprotective Research, Reconstitution & Administration (2026).

What makes VIP particularly compelling to researchers is its remarkable breadth of activity. Few endogenous peptides simultaneously function as a neurotransmitter, immunomodulator, smooth muscle relaxant, secretagogue, and circadian clock synchronizer. This multifunctionality, combined with the discovery that VIP is produced not only by neurons but also by immune cells themselves, has positioned it as a key molecule at the intersection of the nervous and immune systems — the neuroimmune axis.

This research profile provides a comprehensive overview of VIP's molecular structure, receptor pharmacology, physiological functions, and the expanding body of evidence supporting its significance across multiple research domains.

Molecular Structure and Biosynthesis

Primary Structure

VIP is a linear, highly basic peptide consisting of 28 amino acid residues with the sequence:

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

The C-terminal amidation is essential for full biological activity. VIP adopts an alpha-helical conformation in solution, particularly in the C-terminal region (residues 7–28), which is critical for receptor binding and activation (Gozes et al., 1999).

Gene and Processing

VIP is encoded by the VIP gene located on human chromosome 6q25. The prepro-VIP precursor protein also gives rise to peptide histidine methionine (PHM) in humans (or peptide histidine isoleucine, PHI, in other species), another bioactive peptide with partially overlapping functions. This co-expression from a single gene ensures coordinated release of both neuropeptides in tissues where the VIP gene is expressed (Tsukada et al., 1985).

Structural Relationships

VIP belongs to the secretin/glucagon superfamily of peptides, sharing significant sequence homology with:

• •PACAP (Pituitary Adenylate Cyclase-Activating Peptide) — 68% sequence identity; shares receptors with VIP
• •Secretin — founding member of the family
• •Glucagon and GLP-1 — related metabolic peptides
• •GHRH (Growth Hormone-Releasing Hormone) — structurally related

This evolutionary conservation across the superfamily suggests ancient origins and fundamental physiological importance. The high degree of VIP sequence conservation across mammalian species (nearly identical between human, rat, and porcine VIP) further underscores its essential biological roles.

Receptor Pharmacology

VPAC1 and VPAC2 Receptors

VIP exerts its biological effects primarily through two G protein-coupled receptors (GPCRs) belonging to the class B (secretin) receptor family:

VPAC1 Receptor (VIPR1)

• •Binds VIP and PACAP with equal, high affinity (Kd ≈ 1 nM)
• •Widely expressed: lung, liver, intestine, T lymphocytes, brain cortex
• •Primary coupling: Gαs → adenylyl cyclase → cAMP/PKA pathway
• •Also activates PLC/IP₃/Ca²⁺ signaling in some cell types
• •Major mediator of VIP's immunomodulatory effects

VPAC2 Receptor (VIPR2)

• •Also binds VIP and PACAP with comparable affinity
• •Expression pattern: CNS (suprachiasmatic nucleus, thalamus), smooth muscle, pancreas
• •Primary coupling: Gαs → adenylyl cyclase → cAMP/PKA pathway
• •Critical for circadian rhythm regulation in the SCN
• •Mediates smooth muscle relaxation and pancreatic secretion

Both receptors activate adenylyl cyclase, leading to intracellular cAMP accumulation and protein kinase A (PKA) activation as the primary signaling cascade. However, downstream signaling can diverge significantly depending on cell type, receptor density, and the availability of receptor activity-modifying proteins (RAMPs) (Harmar et al., 2012; Couvineau & Laburthe, 2012).

Distinction from PAC1

A third related receptor, PAC1, preferentially binds PACAP over VIP (>100-fold selectivity) and is therefore not considered a primary VIP receptor. This selectivity provides a pharmacological basis for distinguishing PACAP-specific versus VIP/PACAP-shared signaling pathways in research models.

Signal Transduction Cascades

The downstream signaling initiated by VIP receptor activation includes:

• •cAMP/PKA pathway — primary effector for most VIP actions
• •ERK1/2 MAPK — implicated in VIP's circadian clock regulation
• •PI3K/Akt — contributes to neuroprotective signaling
• •NF-κB inhibition — central to anti-inflammatory effects
• •CREB phosphorylation — mediates gene expression changes in neurons

Research using selective VPAC1 and VPAC2 agonists and antagonists has been instrumental in dissecting receptor-specific contributions to VIP's diverse physiological effects (Dickson & Finlayson, 2009).

Tissue Distribution

VIP is one of the most widely distributed neuropeptides in the body, found in both the central and peripheral nervous systems as well as in non-neuronal tissues:

Central Nervous System

• •Cerebral cortex — bipolar interneurons
• •Hippocampus — GABAergic interneurons co-expressing VIP
• •Hypothalamus — suprachiasmatic nucleus (SCN), paraventricular nucleus
• •Brainstem — various nuclei
• •Spinal cord — dorsal horn neurons

Peripheral Nervous System

• •Enteric nervous system — VIPergic neurons throughout the GI tract
• •Parasympathetic ganglia — extensive VIP innervation
• •Sensory neurons — select populations

Non-Neuronal Sources

• •Immune cells — T lymphocytes, macrophages, mast cells, eosinophils
• •Endocrine cells — pancreatic D2 cells
• •Epithelial cells — airway epithelium

The dual neuronal and immune cell origin of VIP is particularly significant for neuroimmune research, as it enables both paracrine and autocrine signaling loops within immune tissues.

Circadian Rhythm Regulation

VIP as the Master Clock Synchronizer

One of VIP's most actively investigated roles is as an essential synchronizing signal within the suprachiasmatic nucleus (SCN), the body's master circadian pacemaker. VIP-expressing neurons constitute approximately 10–24% of SCN neurons and are concentrated in the ventrolateral (core) region of the SCN, which receives direct retinal input via the retinohypothalamic tract.

Research has established that VIP signaling through VPAC2 receptors is critical for:

1. Intercellular synchronization — VIP coordinates the phase of individual SCN neuronal oscillators, enabling coherent circadian output. Without VIP, individual SCN neurons lose synchrony and free-run at different periods (Aton et al., 2005).

2. Light entrainment — VIP neurons relay photic information from the retina to the broader SCN network, enabling the circadian clock to align with the environmental light-dark cycle.

3. Seasonal encoding — VIP contributes to photoperiodic adaptation by modulating the phase relationships between SCN neuronal subpopulations (Lucassen et al., 2012).

Evidence from VIP-Deficient Models

Studies in VIP knockout models have revealed profound circadian disruption:

• •Loss of coordinated behavioral rhythms in constant darkness
• •Dampened or arrhythmic clock gene expression (Per1, Per2, Bmal1) in the SCN
• •Disrupted peripheral clock synchronization in liver, lung, and other organs
• •Altered sleep-wake architecture

These findings demonstrate that VIP is not merely a modulator but an indispensable component of mammalian circadian timekeeping (Vosko et al., 2007; Coomans et al., 2011).

ERK1/2 and DUSP4 Signaling

A landmark 2019 study published in Nature Communications demonstrated that VIP controls the SCN clock network via ERK1/2 and DUSP4 (dual-specificity phosphatase 4) signaling. VIP-induced ERK1/2 activation was shown to be essential for resetting the molecular clock, while DUSP4 acts as a negative feedback regulator that gates the magnitude of VIP-induced phase shifts. This work revealed a previously unknown signaling mechanism underlying circadian entrainment ([Hamnett et al., 2019]()).

Structural Plasticity

Recent research published in Current Biology (2024) demonstrated a remarkable phenomenon: VIPergic fibers within the SCN exhibit a circadian rhythm of structural expansion and retraction. This finding represents a novel form of circadian structural plasticity, suggesting that VIP signaling in the SCN involves not just neurochemical but also anatomical reorganization on a daily basis.

Immunomodulatory Functions

Anti-Inflammatory Mechanisms

VIP has been extensively characterized as an endogenous anti-inflammatory neuropeptide, capable of modulating both innate and adaptive immune responses. Its immunomodulatory effects are primarily mediated through VPAC1 receptors expressed on immune cells (Delgado et al., 2004).

Key anti-inflammatory mechanisms include:

Innate Immunity

• •Inhibition of macrophage activation and pro-inflammatory cytokine production (TNF-α, IL-6, IL-12, iNOS)
• •Promotion of anti-inflammatory cytokine release (IL-10)
• •Suppression of NLRP3 inflammasome activation
• •Modulation of macrophage polarization — shifting from M1 (pro-inflammatory) toward M2 (anti-inflammatory/reparative) profiles (Leceta et al., 2016)

Adaptive Immunity

• •Promotion of regulatory T cell (Treg) differentiation
• •Inhibition of Th1/Th17 pro-inflammatory responses
• •Modulation of dendritic cell maturation and antigen presentation
• •Regulation of B cell function and immunoglobulin production

NF-κB Pathway Inhibition

A central mechanism underlying VIP's anti-inflammatory action is the inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), a master transcription factor for inflammatory gene expression. VIP achieves this through multiple routes:

• •Stabilization of IκBα (the NF-κB inhibitor)
• •Reduction of NF-κB nuclear translocation
• •Competition with pro-inflammatory signaling cascades via cAMP elevation

Autoimmune Research Applications

The potent immunomodulatory properties of VIP have generated significant research interest in autoimmune disease models. In vitro and in vivo studies have demonstrated VIP's effects in experimental models of:

• •Rheumatoid arthritis — reduction of joint inflammation and tissue damage
• •Septic shock — improved survival with TNF-α/IL-6 suppression
• •Inflammatory bowel disease — attenuation of colitis severity
• •Multiple sclerosis — reduced CNS inflammatory infiltration

These findings have positioned VIP as an endogenous regulator at the neuroimmune interface, with ongoing research investigating VIP analogs and delivery strategies for improved pharmacokinetic properties (Gonzalez-Rey et al., 2007; Delgado et al., 2002; Jimeno et al., 2019).

Neuroprotective Research

Mechanisms of Neuroprotection

VIP has demonstrated robust neuroprotective properties in multiple in vitro and in vivo research models. Its neuroprotective actions operate through both direct and indirect mechanisms:

Direct neuroprotection:

• •Promotion of neuronal survival via BDNF and activity-dependent neuroprotective protein (ADNP) upregulation
• •Anti-apoptotic signaling through PI3K/Akt activation
• •Calcium homeostasis regulation
• •Antioxidant enzyme induction

Indirect neuroprotection (glia-mediated):

• •Stimulation of neurotrophic factor release from astrocytes
• •Inhibition of microglial activation and neuroinflammation
• •Reduction of neurotoxic mediator production (ROS, NO, glutamate)

Research by Delgado and colleagues has shown that VIP inhibits beta-amyloid-induced neurodegeneration by suppressing microglial production of pro-inflammatory and neurotoxic factors, suggesting a role as an endogenous neuroprotective agent that bridges immune and neuronal signaling (Delgado et al., 2008).

Neurodegenerative Disease Models

Alzheimer's Disease Research

VIP research in AD models has yielded compelling findings. In the 5xFAD transgenic mouse model, VIP administration was associated with decreased beta-amyloid accumulation and attenuated brain atrophy, suggesting neuroprotective effects mediated through both amyloid clearance and neuroinflammation reduction (Korkmaz et al., 2019).

Earlier work identified a core tetrapeptide sequence within VIP (residues Lys-Tyr-Leu-Asn, corresponding to positions 20–23) as the minimal neuroprotective fragment. This discovery led to the design of stearyl-Nle17-VIP (SNV), a lipophilic superactive analog with approximately 100-fold greater potency than native VIP in neuroprotection assays (Gozes et al., 2000; Gozes et al., 1999).

Parkinson's Disease Research

VIP has shown neuroprotective effects against 6-OHDA-induced neurotoxicity in dopaminergic neuron culture systems, a widely used model for Parkinson's disease research. The protective mechanism appears to involve both direct anti-apoptotic effects and indirect modulation of microglial inflammatory responses (Gozes et al., 2000).

Broader Neurological Research

A comprehensive review cataloged VIP's neuroprotective effects across multiple injury models, including excitotoxicity, oxidative stress, and inflammatory neurodegeneration. The peptide's ability to simultaneously target neuroinflammation, oxidative damage, and apoptotic pathways makes it a unique research tool for studying multipronged neuroprotective strategies (Dejda et al., 2005; Gonzalez-Rey et al., 2012).

Cardiopulmonary Research

Vasodilatory Properties

VIP was originally discovered and named for its potent vasodilatory action. It remains one of the most potent endogenous vasodilators identified, capable of relaxing vascular smooth muscle in virtually every vascular bed studied. This vasodilation is mediated primarily through:

• •cAMP-dependent relaxation of vascular smooth muscle
• •Stimulation of endothelial nitric oxide (NO) release
• •Direct smooth muscle VPAC receptor activation

Pulmonary Vascular Research

VIP has attracted particular attention in pulmonary vascular research. Studies have demonstrated that:

• •VIP-deficient models develop spontaneous pulmonary vascular remodeling and features resembling pulmonary arterial hypertension (PAH)
• •The mechanism involves uncontrolled activation of calcineurin-NFAT signaling in the absence of VIP's inhibitory tone
• •Inhaled VIP administration in research settings has been shown to reduce pulmonary vascular resistance

The VIP gene has been proposed as a key modulator of pulmonary vascular remodeling and inflammation, linking its vasodilatory and anti-inflammatory properties in the pulmonary circulation (Said, 2003; Said, 2008).

Bronchodilation

In the airways, VIP functions as a non-adrenergic, non-cholinergic (NANC) inhibitory neurotransmitter, mediating bronchial smooth muscle relaxation. This bronchodilatory action has made VIP relevant to airway physiology research, particularly in studies investigating the NANC nervous system's role in airway caliber regulation.

Gastrointestinal Functions

Enteric Nervous System

VIP is one of the most abundant neuropeptides in the enteric nervous system (ENS), often referred to as the "gut brain." VIPergic neurons are found throughout the gastrointestinal tract, from esophagus to colon, and play essential roles in:

• •Intestinal secretion — VIP stimulates chloride and water secretion via VPAC1 receptor activation on enterocytes, activating the cAMP/PKA/CFTR pathway
• •Smooth muscle relaxation — VIP mediates descending relaxation in peristaltic reflexes
• •Sphincter control — VIP-mediated relaxation of the lower esophageal sphincter, pylorus, and internal anal sphincter
• •Blood flow regulation — vasodilation of mesenteric vessels
• •Mucosal protection — cytoprotective effects on the intestinal epithelium

VIP-deficient models exhibit significant gastrointestinal dysfunction, including delayed gastric emptying, altered intestinal transit, and disrupted mucosal homeostasis, underscoring VIP's fundamental role in gut physiology (Iwasaki et al., 2019).

Pancreatic Research

In the pancreas, VIP stimulates both exocrine secretion (bicarbonate and enzyme output) and modulates endocrine function. VIP-containing neurons innervate pancreatic islets, and VPAC2 receptor activation has been shown to potentiate glucose-stimulated insulin secretion, positioning VIP as a relevant molecule in metabolic and diabetes research.

Pharmacological Considerations in Research

Stability and Half-Life

Native VIP has a short circulating half-life (approximately 1–2 minutes) due to rapid enzymatic degradation by:

• •Neutral endopeptidase (NEP/CD10) — primary degradation enzyme
• •Dipeptidyl peptidase IV (DPP-IV)
• •Serine proteases — trypsin and chymotrypsin-like enzymes

This rapid degradation has driven significant research into VIP analogs with improved metabolic stability, including:

• •Stearyl-VIP — lipidated analog with enhanced membrane association
• •[Ala11,22,28]-VIP — substituted analog resistant to enzymatic cleavage
• •VIP-containing nanoparticles — sustained-release formulations
• •PEGylated VIP — polyethylene glycol conjugates

Reconstitution and Handling

For laboratory applications, VIP is typically supplied as a lyophilized powder and should be reconstituted in sterile deionized water or dilute acetic acid (0.1%) to prevent adsorption to glass and plastic surfaces. Researchers can consult verified supplier reviews for peer feedback on VIP sourcing quality and peptide activity consistency. Due to its basic nature (pI of approximately 9.4), VIP can adhere to negatively charged surfaces, necessitating the use of siliconized tubes or carrier protein supplementation in dilute solutions.

Storage Stability

• •Lyophilized: stable at -20 degrees Celsius for extended periods
• •Reconstituted stock solutions: store at -80 degrees Celsius in single-use aliquots
• •Avoid repeated freeze-thaw cycles, which significantly reduce bioactivity
• •Working solutions should be prepared fresh and used within hours

For detailed guidance on peptide handling, refer to our Peptide Storage Best Practices guide.

Relationship to Other Research Peptides

VIP exists within a broader network of neuropeptides and immunomodulatory compounds relevant to peptide research:

• •Selank — another neuropeptide with immunomodulatory and anxiolytic research applications, operating through different receptor systems
• •Thymosin Alpha 1 — thymic peptide with complementary immunomodulatory research profiles
• •LL-37 — antimicrobial peptide with overlapping immunomodulatory research interest
• •Thymulin — zinc-dependent peptide involved in immune regulation research
• •MOTS-c — mitochondrial-derived peptide with metabolic research applications

Current Research Frontiers

VIP Analogs and Peptidomimetics

The development of metabolically stable VIP analogs remains an active area of investigation. Researchers are exploring:

• •Cyclized VIP fragments with improved receptor selectivity
• •Non-peptide VPAC receptor agonists for oral bioavailability
• •VIP-albumin fusion proteins for extended circulation
• •Targeted nanoparticle delivery systems

Neuroimmune Cross-Talk

VIP's position at the neuroimmune interface has made it a focus of research into:

• •Gut-brain axis communication
• •Stress-immune interactions
• •Circadian modulation of immune function (chrono-immunology)
• •Neuroinflammation in aging and neurodegeneration

Chronobiology

Recent discoveries about VIP's role in SCN structural plasticity and seasonal adaptation continue to expand the understanding of circadian timekeeping mechanisms. The finding that VIPergic fibers physically remodel on a circadian basis opens new questions about neuropeptide signaling dynamics.

Research Considerations

VIP is classified as a research chemical intended for laboratory investigation only. All experimental work should be conducted in accordance with institutional protocols, ethical guidelines, and applicable regulations governing peptide research.

Researchers working with VIP should be aware of:

• •Species considerations — while VIP sequence is highly conserved across mammals, receptor expression patterns and signaling responses may vary between species
• •Context-dependent effects — VIP can produce opposing effects depending on the inflammatory milieu, receptor expression levels, and cell activation state
• •Receptor cross-reactivity — PACAP shares VIP receptors, necessitating careful experimental design to distinguish VIP-specific from PACAP-shared effects

Conclusion

Vasoactive intestinal peptide stands as one of the most functionally diverse neuropeptides in the mammalian signaling repertoire. From its essential role in synchronizing the body's master circadian clock to its potent immunomodulatory and neuroprotective properties, VIP continues to generate significant research interest across neuroscience, immunology, chronobiology, and cardiovascular research.

The ongoing development of stabilized analogs and novel delivery strategies, combined with advances in single-cell and optogenetic technologies for dissecting VIP circuit function, positions this peptide for continued prominence in biomedical research. As our understanding of neuroimmune cross-talk deepens, VIP's unique role as an endogenous mediator bridging the nervous and immune systems ensures its relevance to some of the most important questions in modern biology.

Research Tools

Researchers sourcing this peptide for laboratory investigation can use the peptide price comparison tool to identify research-grade material from verified suppliers. See community supplier reviews for researcher feedback on purity and documentation quality. For reconstitution planning, the peptide calculator provides molar mass, concentration, and dilution calculations.

References

2. Tsukada T, et al. Structure of the human vasoactive intestinal polypeptide gene. DNA. 1985;4(4):293-300. PubMed

3. Gozes I, et al. A new concept in the pharmacology of neuroprotection. J Mol Neurosci. 2000;14(1-2):61-68. PubMed

4. Harmar AJ, et al. Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions. Amino Acids. 2013;44(5):1245-1255. PubMed

5. Couvineau A, Laburthe M. VPAC receptors: structure, molecular pharmacology and interaction with accessory proteins. Br J Pharmacol. 2012;166(1):42-50. PubMed

6. Aton SJ, et al. Vasoactive intestinal polypeptide mediates circadian rhythmicity and synchrony in mammalian clock neurons. Nat Neurosci. 2005;8(4):476-483. PubMed

7. Vosko AM, et al. Vasoactive intestinal peptide and the mammalian circadian system. Gen Comp Endocrinol. 2007;152(2-3):165-175. PubMed

8. Coomans CP, et al. Effects of VIP genotype on circadian gene expression in the SCN and peripheral organs. J Biol Rhythms. 2011;26(2):154-164. PubMed

10. Lucassen EA, et al. Role of VIP in seasonal encoding by the SCN clock. Eur J Neurosci. 2012;35(9):1466-1474. PubMed

11. Delgado M, et al. The significance of vasoactive intestinal peptide in immunomodulation. Pharmacol Rev. 2004;56(2):249-290. PubMed

12. Leceta J, et al. VIP impairs acquisition of the macrophage proinflammatory polarization profile. J Leukoc Biol. 2016;100(6):1385-1393. PubMed

13. Gonzalez-Rey E, et al. Emerging roles of VIP: a new approach for autoimmune therapy. Ann Rheum Dis. 2007;66 Suppl 3:iii70-iii76. PubMed

14. Delgado M, et al. VIP in the immune system: potential therapeutic role in inflammatory and autoimmune diseases. J Mol Med. 2002;80(1):16-24. PubMed

15. Jimeno R, et al. A clinical approach for the use of VIP axis in inflammatory and autoimmune diseases. Int J Mol Sci. 2019;21(1):65. PubMed

16. Delgado M, et al. VIP protects against beta-amyloid-induced neurodegeneration by inhibiting microglia activation at multiple levels. Glia. 2008;56(10):1091-1103. PubMed

17. Korkmaz OT, et al. VIP decreases beta-amyloid accumulation and prevents brain atrophy in the 5xFAD mouse model. J Mol Neurosci. 2019;68(3):389-396. PubMed

18. Gozes I, et al. VIP prevents neurotoxicity in neuronal cultures: relevance to neuroprotection in Parkinson's disease. Brain Res. 2000;854(1-2):257-262. PubMed

19. Dejda A, et al. Role of VIP in inflammation and autoimmunity. Curr Pharm Des. 2005;11(8):997-1004. PubMed

20. Gonzalez-Rey E, et al. VIP in neurological diseases: more than a neuropeptide. FASEB J. 2012;26(12):4688-4698. PubMed

21. Said SI. VIP as a new drug for treatment of primary pulmonary hypertension. J Clin Invest. 2003;111(9):1339-1346. PubMed

22. Said SI. The VIP gene is a key modulator of pulmonary vascular remodeling and inflammation. Ann N Y Acad Sci. 2008;1144:148-153. PubMed

23. Iwasaki M, et al. Recent advances in VIP physiology and pathophysiology: focus on the gastrointestinal system. F1000Res. 2019;8:F1000 Faculty Rev-1629. PubMed

24. Dickson L, Finlayson K. Therapeutic potential of VIP and its receptors in neurological disorders. CNS Neurol Disord Drug Targets. 2009;8(5):349-357. PubMed

25. Tan YV, et al. The neuropeptide VIP: direct effects on immune cells and involvement in inflammatory and autoimmune diseases. Acta Physiol. 2015;213(2):315-338. PubMed

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Further Reading:

• •PACAP (Pituitary Adenylate Cyclase-Activating Polypeptide): The Pleiotropic Neuropeptide Driving Neuroscience and Stress Research
• •CGRP (Calcitonin Gene-Related Peptide): The Vasodilatory Neuropeptide Bridging Pain, Cardiovascular, and Tissue Repair Research
• •Galanin: The Pleiotropic Neuropeptide Bridging Neuroscience, Metabolic, Pain, and Oncology Research
• •Neuropeptide Y (NPY): The Pleiotropic Hypothalamic Peptide Driving Appetite, Cardiovascular, and Cancer Research
• •Reconstitution Calculator
• •Peptide Stack Builder

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Where to Source VIP for Research: Live Supplier Pricing

Vasoactive intestinal peptide is available from multiple verified research suppliers. The table below reflects current in-stock pricing from the peptides.so supplier network (data pulled 2026-07-27). Prices shown are per mg for lyophilized powder.

Market range: $6.90–$23.60/mg across 61 active listings. The 10mg vial format offers the best per-mg economy at most suppliers.

> View real-time prices and compare across all verified suppliers: VIP Peptide Supplier Comparison

VIP is a moderately priced research neuropeptide relative to its complexity (28-amino acid sequence, C-terminal amidation). Budget for high-purity (≥98%) HPLC-verified material for receptor binding and cellular signaling experiments, where impurities can confound results.

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Frequently Asked Questions

Q: Is VIP the same as PACAP?

A: No, though they are closely related. VIP and PACAP both belong to the secretin/glucagon superfamily and share receptors (VPAC1 and VPAC2), but PACAP also binds the PAC1 receptor selectively. They share about 68% sequence identity. VIP is 28 amino acids; PACAP comes in 27- and 38-amino-acid forms. See the PACAP research profile for a full comparison.

Q: What receptors does VIP bind to?

A: VIP acts on three G protein-coupled receptors: VPAC1 (expressed broadly in lung, liver, T-cells), VPAC2 (high expression in smooth muscle, pancreas, brain), and PAC1 (PACAP-preferring, also binds VIP at higher concentrations). All three signal primarily through cAMP via Gs coupling, though β-arrestin pathways have also been described.

Q: Is VIP stable in solution?

A: VIP has moderate solution stability. Lyophilized powder stored at −20°C is stable for years; reconstituted solutions are typically stable 24–48 hours at 4°C with 1% BSA or 0.1% acetic acid as carrier. Avoid repeated freeze-thaw cycles. Use bacteriostatic water or 0.1% acetic acid for reconstitution in research protocols.

Q: What are the main research areas for VIP?

A: The three most active research fronts as of 2026 are: (1) neuroimmune regulation — VIP as a potent anti-inflammatory in models of autoimmune disease and neuroinflammation; (2) circadian biology — VIP synchronizes SCN pacemaker neurons and may be relevant to circadian rhythm disorders; (3) pulmonary physiology — VIP deficiency correlates with pulmonary arterial hypertension in some models. See the sections above for detailed citations.

Q: How does VIP differ from substance P?

A: VIP and substance P are often studied together as opposing modulators: VIP is predominantly anti-inflammatory and vasodilatory, while substance P is pro-inflammatory and promotes vasodilation via NK1 receptors. In gastrointestinal research, they act as co-transmitters with opposing effects on motility. See Neuropeptide Y for another key hypothalamic comparator.

Q: What purity is required for receptor binding studies?

A: ≥98% HPLC purity is standard for receptor pharmacology work. Confirm molecular weight by mass spectrometry (expected MW: ~3326 Da for the 28-aa amidated form). Certificate of Analysis (CoA) with both HPLC trace and MS data should be requested before purchase for any in vitro receptor binding experiment.

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For research purposes only. VIP is a research chemical for laboratory investigation only. Not for human or animal administration.

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Supporting Citations

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(PMID: 41925448)