≥98%HPLC Purity
COAIncluded
USAShipped
VIP (Vasoactive Intestinal Peptide) Peptide
28-amino acid neuropeptide with pleiotropic functions across immune, nervous, and gastrointestinal systems. Activates VPAC1 and VPAC2 receptors (class B GPCRs) to regulate inflammation, circadian rhythm, neuroprotection, bronchodilation, and gut motility. One of the most multi-functional endogenous peptides known.
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| SKU | ACR-VIP |
|---|---|
| CAS Number | 37221-79-7 |
| Molecular Formula | C147H237N43O44S |
| Molecular Weight | 3,326.83 g/mol |
| 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 |
| Purity | ≥98% |
| Physical Form | Lyophilized Powder |
| Storage | Store at -20°C |
What is Vasoactive Intestinal Peptide (VIP)?
Vasoactive Intestinal Peptide (VIP) is an endogenous 28-amino acid neuropeptide with the sequence HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH₂, molecular weight 3,326.83 g/mol, and CAS number 37221-79-7. First isolated from porcine duodenum by Said and Mutt in 1970, VIP is now recognized as one of the most widely distributed and functionally diverse neuropeptides in the human body.
VIP is expressed throughout the central and peripheral nervous systems, the gastrointestinal tract, the respiratory system, and immune tissues. It acts through two G protein-coupled receptors — VPAC1 (widely distributed) and VPAC2 (more restricted to CNS, pancreas, and immune cells) — both coupling to Gs and activating adenylyl cyclase/cAMP signaling.
In recent years, VIP has gained significant research attention for its potent anti-inflammatory properties, neuroprotective effects, and role in mold/biotoxin illness (Chronic Inflammatory Response Syndrome, CIRS). Dr. Ritchie Shoemaker's CIRS protocol uses VIP as a final-step treatment for persistent inflammation, bringing widespread awareness to this previously underappreciated neuropeptide.
Mechanism of Action
VPAC1 Receptor (widely distributed): VIP binds VPAC1 with Kd ≈ 1 nM, activating Gs → adenylyl cyclase → cAMP → PKA. VPAC1 is expressed on immune cells (T-cells, macrophages, dendritic cells), neurons, epithelial cells, and vascular smooth muscle. Activation produces: vasodilation, bronchodilation, anti-inflammatory cytokine shift (IL-10 up, TNF-α/IL-6 down), and neuroprotection.
VPAC2 Receptor (restricted): Expressed primarily in the suprachiasmatic nucleus (SCN, circadian pacemaker), pancreatic beta cells, and specific immune cell subsets. VPAC2 activation regulates circadian gene expression (Per1, Per2), glucose-stimulated insulin secretion, and Th2 immune polarization.
Anti-Inflammatory Cascade: VIP is one of the most potent endogenous anti-inflammatory peptides known. It inhibits NF-κB activation in macrophages, shifts Th1→Th2 balance, promotes regulatory T-cell (Treg) differentiation, reduces costimulatory molecule expression on antigen-presenting cells, and inhibits NLRP3 inflammasome activation. This broad anti-inflammatory profile explains its efficacy in autoimmune and chronic inflammatory disease models.
Research & Clinical Studies
VIP and CIRS/Biotoxin Illness Research
VIP gained widespread clinical research attention through Dr. Ritchie Shoemaker's work on Chronic Inflammatory Response Syndrome (CIRS) — a multi-system inflammatory condition triggered by biotoxin exposure (mold, Lyme, cyanobacteria). VIP is used as the final step in the Shoemaker Protocol after other interventions fail to normalize inflammatory markers.
Key findings in CIRS research:
- VIP nasal spray (50 mcg 4x daily) normalized elevated TGF-β1, MMP-9, MSH, and VEGF levels in CIRS patients
- Resolved persistent cognitive symptoms ("brain fog") in 90%+ of treated patients
- Improved pulmonary function (elevated PASP normalized)
- Restored quality of life measures in treatment-refractory CIRS cases
- Mechanism: VIP reverses the chronic inflammatory cascade by resetting cytokine balance and restoring regulatory immune function
[1] Shoemaker RC et al. Vasoactive intestinal polypeptide (VIP) corrects chronic inflammatory response syndrome (CIRS) acquired following exposure to water-damaged buildings. Health. 2013;5(3):396-401. PubMed ↗
VIP and Neuroprotection Research
VIP has demonstrated potent neuroprotective effects across multiple neurodegenerative and neuroinflammatory models:
- Alzheimer's disease: VIP protected hippocampal neurons from amyloid-beta toxicity, reduced microglial activation, and improved cognitive performance in transgenic AD mice
- Parkinson's disease: Protected dopaminergic neurons from MPTP-induced death, preserved striatal dopamine levels
- Multiple sclerosis: Reduced demyelination and inflammatory infiltration in EAE (experimental autoimmune encephalomyelitis) model — the gold-standard MS model
- Traumatic brain injury: Reduced cerebral edema, inflammatory cytokines, and neuronal apoptosis in TBI models
The neuroprotective mechanism involves both direct neuronal survival signaling (cAMP/PKA → CREB → BDNF) and indirect protection via suppression of neuroinflammation (microglial NF-κB inhibition).
[1] Dejda A et al. Neuroprotective potential of three neuropeptides PACAP, VIP and PHI. Pharmacol Rep. 2005;57(3):307-320. PubMed ↗
VIP and Pulmonary/Respiratory Research
VIP is a potent bronchodilator and pulmonary vasodilator with anti-inflammatory properties in the airways:
- Bronchodilation: VIP relaxes airway smooth muscle via cAMP-mediated inhibition of myosin light chain kinase, with potency comparable to beta-2 agonists
- Pulmonary hypertension: VIP reduces pulmonary artery pressure (PASP) by activating VPAC1 on pulmonary vascular smooth muscle. CIRS patients with elevated PASP showed normalization with intranasal VIP
- Asthma: VIP reduces airway hyperresponsiveness, mucus hypersecretion, and eosinophilic infiltration in allergic asthma models
- Lung inflammation: Suppresses alveolar macrophage activation and reduces acute lung injury severity
VIP and Gastrointestinal Research
As its name implies, VIP was originally discovered for its gastrointestinal effects. It is one of the primary non-adrenergic, non-cholinergic (NANC) neurotransmitters in the enteric nervous system:
- Secretion: VIP stimulates water and electrolyte secretion in the intestinal epithelium (the cause of VIPoma-associated watery diarrhea)
- Motility: Relaxes GI smooth muscle, reducing contractile amplitude and frequency (prokinetic in sphincters, inhibitory in circular muscle)
- Mucosal protection: Enhances mucosal blood flow and mucus production, protecting against NSAID-induced and stress-related mucosal damage
- Inflammatory bowel disease: VIP reduces colonic inflammation in both DSS-colitis and TNBS-colitis models (Th1-mediated IBD models), decreasing tissue damage scores and inflammatory infiltration
[1] Abad C et al. Therapeutic effects of vasoactive intestinal peptide in the trinitrobenzene sulfonic acid mice model of Crohn disease. Gastroenterology. 2003;124(4):961-971. PubMed ↗
VIP and Circadian Rhythm Research
VIP is essential for maintaining circadian rhythm synchronization in the suprachiasmatic nucleus (SCN). VPAC2 receptors on SCN neurons mediate VIP's role as the primary intercellular coupling signal that synchronizes the ~20,000 clock neurons into a coherent circadian output.
- VIP-deficient mice show fragmented sleep, disrupted activity patterns, and dampened circadian gene oscillation
- VIP application restores synchronization of desynchronized SCN slice cultures within 24 hours
- In CIRS patients, disrupted sleep architecture often resolves with VIP treatment, likely reflecting restored SCN function
Chemical & Physical Properties
| Full Name | Vasoactive Intestinal Peptide (VIP) |
|---|---|
| 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 |
| Molecular Formula | C₁₄₇H₂₃₇N₄₃O₄₄S |
| Molecular Weight | 3,326.83 g/mol |
| CAS Number | 37221-79-7 |
| Amino Acids | 28 |
| C-terminus | Amidated (-NH₂) |
| Receptors | VPAC1 (Kd ≈ 1 nM) and VPAC2 (Kd ≈ 1 nM) |
| Signal Pathway | Gs → adenylyl cyclase → cAMP → PKA |
| Half-life | ~1-2 minutes in plasma (rapid DPP-IV degradation) |
| Purity | ≥98% HPLC |
Handling & Reconstitution Guidelines
Reconstitution: Add bacteriostatic water slowly along vial wall. VIP is a 28-amino acid peptide that dissolves within 5 minutes. Do not shake — gentle rolling if needed.
Concentration: 5 mg vial + 1 mL BAC water = 5 mg/mL.
Intranasal preparation: For nasal spray research protocols (as used in CIRS research), VIP is typically dissolved in preservative-free sterile saline. Standard research concentration: 50 mcg per spray actuation.
Important: VIP contains methionine (position 17) — susceptible to oxidation. Protect from light and minimize air exposure. The peptide has a very short plasma half-life (~1-2 min) due to rapid DPP-IV degradation — intranasal route bypasses first-pass metabolism.
Storage & Stability
Lyophilized: -20°C for 24 months, 2-8°C for 6 months.
Reconstituted: 2-8°C, use within 14 days. Protect from light (Met17 oxidation).
Note: VIP is more degradation-prone than smaller peptides due to its 28-amino acid length and methionine content. For long-term reconstituted storage, aliquot into single-use volumes to avoid repeated air/light exposure.
Frequently Asked Questions
What is VIP used for in CIRS research?
In Dr. Shoemaker's CIRS protocol, VIP nasal spray (50 mcg 4x daily) is the final treatment step for patients with persistent inflammation after other interventions. It normalizes elevated inflammatory markers (TGF-β1, MMP-9, VEGF, C4a) and resolves cognitive symptoms in >90% of treatment-refractory CIRS cases.
What receptors does VIP activate?
VIP activates two class B GPCRs: VPAC1 (widely distributed — immune cells, neurons, epithelium, vasculature) and VPAC2 (restricted to SCN, pancreas, specific immune cells). Both couple to Gs → cAMP → PKA. VPAC1 mediates most anti-inflammatory and vasodilatory effects.
How is VIP administered in research?
VIP is most commonly administered intranasally in clinical research (as in CIRS protocols) because: it bypasses the ~1-2 minute plasma half-life limitation, achieves direct CNS delivery via olfactory mucosa, and avoids GI degradation. Injectable (SC, IV) routes are used in acute preclinical studies.
Why does VIP have such a short half-life?
VIP is rapidly degraded by dipeptidyl peptidase IV (DPP-IV) and neutral endopeptidase (NEP) in plasma, giving it a half-life of only 1-2 minutes intravenously. This is why intranasal delivery (bypassing systemic degradation) is the preferred research route for chronic protocols.
What is the difference between VIP and PACAP?
VIP and PACAP share 68% sequence homology and both activate VPAC1/VPAC2 receptors. However, PACAP also activates PAC1 receptor (VIP does not). PACAP is more potent for neuroprotection; VIP is more potent for anti-inflammation and has better characterized clinical CIRS data.
Is VIP the same as VIPoma peptide?
Yes — VIPomas are tumors that overproduce VIP, causing Verner-Morrison syndrome (watery diarrhea, hypokalemia, achlorhydria). This was actually how VIP's GI secretory function was first characterized clinically. At therapeutic research doses, VIP does not cause the extreme secretory effects seen in VIPoma.
What is the molecular weight and CAS of VIP?
VIP has molecular weight 3,326.83 g/mol, molecular formula C₁₄₇H₂₃₇N₄₃O₄₄S, and CAS number 37221-79-7. It is a 28-amino acid neuropeptide with a C-terminal amide group essential for receptor binding.
For laboratory and research use only. Not intended for human or animal consumption. All product information is derived from published preclinical research and does not constitute medical advice or claims.