VIP

Vasoactive Intestinal Peptide (VIP)

Vasoactive Intestinal Peptide (VIP), or vasoactive intestinal polypeptide, is a naturally occurring, highly conserved 28-residue peptide with a complex regulatory profile. Functioning as both a neuromodulator within the nervous system and a peptide hormone secreted by the gut and pancreas, VIP influences virtually all major organ systems. Its biological activity is transduced through its high-affinity receptors, VPAC1 and VPAC2, which belong to the Class II G protein-coupled receptor family.

VIP's diverse actions include:

• Vascular Regulation: It is a potent vasodilator, critical for maintaining appropriate systemic and local blood flow, resulting in reduced blood pressure.
• Cardiopulmonary Function: Enhances cardiac output via positive chronotropic (rate) and inotropic (force) effects, while also acting as a bronchodilator by relaxing smooth muscle in the airways.
• Gut Homeostasis: Regulates gastrointestinal motility and is a key secretagogue, promoting water and electrolyte secretion.
• Neuroendocrine Control: Involved in the regulation of prolactin and the photo-entrainment of the suprachiasmatic nucleus to manage circadian rhythms.
• Cellular Defense: Offers powerful neuroprotective effects, shielding neurons from damage due to ischemia and oxidative stress.
• Immunological Role: Acts as a broad-spectrum anti-inflammatory agent, with specific research showing a unique ability to reduce pathological tissue scarring, or fibrosis.

The research on VIP is vast, driven by its pivotal role in linking the nervous, endocrine, and immune systems, making it an invaluable peptide for studying multifaceted biological regulation.

Vasoactive Intestinal Peptide (VIP) 10mg Overview

Vasoactive Intestinal Peptide (VIP) executes its function through the G protein-coupled receptors VPAC1 and VPAC2, which are expressed across numerous cell types. Receptor occupation leads to the robust activation of the adenylyl cyclase pathway, resulting in a consequential increase in the intracellular second messenger cyclic adenosine monophosphate (cAMP). The resultant cAMP surge is the mechanistic driver for VIP's primary effects, including smooth muscle relaxation and enhanced vasodilation.

A central theme in VIP research is its sophisticated immunomodulatory capacity. The peptide is shown to actively dampen inflammatory cascades by suppressing the production of key pro-inflammatory cytokines and shifting the immune bias. Its tissue-protective actions are currently being explored in numerous research models of chronic inflammation, including pulmonary fibrosis, IBDs (Inflammatory Bowel Diseases), and debilitating neurodegenerative disorders. VIP also contributes significantly to critical physiological control mechanisms, such as synchronization of biological clocks and gastrointestinal fluid transport.

Vasoactive Intestinal Peptide (VIP) Structure

Vasoactive Intestinal Peptide (VIP) is an oligopeptide consisting of 28 amino acid residues. It is structurally homologous with the secretin-glucagon peptide superfamily, possessing a specific sequence that ensures high-affinity binding to its cognate VPAC receptors. The C-terminal amidation (N-terminal-Amide) is a key feature required for full biological potency.

The verified primary structure of Vasoactive Intestinal Peptide (Human, Porcine, Bovine) is:

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-N-terminal-Amide

The calculated chemical formula is: C130H215N43O37S

The approximate molecular weight is 3325.82 g/mol.

Vasoactive Intestinal Peptide (VIP) Research

VIP's dual neuro-immune origin—from immune-associated nerve fibers and immune cells—underscores its critical function in controlling localized and systemic inflammation. Its ability to favor Th2-type immune responses is key to its role as an anti-inflammatory and tissue protective agent.

Gut Inflammation and Epithelial Integrity

In models of chronic inflammatory gut disorders, such as Inflammatory Bowel Diseases (IBDs), VIP provides a potent protective mechanism:

1. Anti-inflammatory Cytokine Induction: VIP stimulates T-cell subsets to produce the anti-inflammatory cytokine Interleukin-10 (IL-10), effectively antagonizing the damaging cascade of Th1-mediated inflammation.
2. Barrier Function: A core pathology of IBD is the breakdown of the intestinal epithelial barrier. VIP is shown to enhance this barrier's stability, thereby reducing the transit of luminal antigens that perpetuate chronic immune activation.

Pulmonary Fibrosis and Airway Dynamics

VIP is studied for its ability to prevent two types of destructive lung pathology: inflammation and structural remodeling:

• Anti-Fibrotic Mechanism: VIP modulates T-cell activity by suppressing the NFAT peptide pathway, a process being investigated for its potential to inhibit the progression of pulmonary fibrosis, the irreversible scarring seen in diseases like COPD and sarcoidosis.
• Airway Control: VIP's ability to inhibit the excessive proliferation of lung smooth muscle cells is a critical research area, suggesting a role in mitigating airway remodeling, which causes progressive functional decline in chronic asthma.

Immunological Tolerance in Transplantation

Research into VIP offers a sophisticated approach to preventing allograft rejection. The peptide specifically targets Dendritic Cells (DCs), the immune system's primary antigen presenters:

• Mitigation of Rejection Signals: VIP significantly reduces the proliferation and activation state of DCs. By selectively promoting DCs associated with non-immunogenic, tolerogenic antigens, VIP helps steer the immune system toward accepting the transplanted tissue, suggesting a more precise and less toxic alternative to systemic immunosuppression.

Neuroprotection and CNS Barrier Function

In the CNS, VIP acts as a pivotal neurotrophic and defensive factor:

• Blood-Brain Barrier (BBB) Stabilization: VIP is essential for maintaining the physical and functional integrity of the BBB, a barrier frequently breached in conditions like stroke, multiple sclerosis, and encephalomyelitis.
• Neurodegenerative Defense: VIP shows promise in mitigating key hallmarks of neurodegeneration, including modulating beta-amyloid accumulation in Alzheimer’s models and providing neuroprotection in Parkinson’s disease by maintaining an anti-inflammatory (Th2) environment. It also supports neuronal myelination and reduces excitotoxic damage to white matter.

Cardiac Fibrosis and Remodeling Reversal

Cardiac fibrosis, the irreversible scarring of the heart muscle, defines the terminal stage of many cardiovascular diseases. VIP offers a distinct research pathway:

• Scar Regression Potential: Preclinical studies suggest VIP not only inhibits the formation of new scar tissue but may actively facilitate the regression of existing cardiac fibrosis. This potent anti-fibrotic effect is mechanistically linked to the suppression of angiotensinogen and the angiotensin receptor type 1a—pathways well-established in the control of cardiac remodeling.

Contemporary Research: VIP Analogs and COVID-19

The synthetic VIP analogue, aviptadil (RLF-100), became a focus of clinical research during the COVID-19 pandemic for treating acute respiratory failure. Its mechanism relies on VIP’s powerful anti-inflammatory effects to suppress the destructive cytokine storm. Crucially, it was studied for its potential to protect the oxygen-exchanging Type II alveolar cells and its hypothesized ability to block the cellular entry of the SARS-CoV-2 virus.

Vasoactive Intestinal Peptide (VIP) Key Research Application Table

Research Focus Area

Specific Target Condition

VIP's Primary Action / Mechanism

Inflammatory Diseases

IBD, Chronic Inflammation

Shifts immune response to anti-inflammatory (Th2); stimulates IL-10.

Fibrotic Disorders

Pulmonary & Cardiac Fibrosis

Suppresses NFAT; reduces Angiotensin Receptor signaling; promotes scar regression.

Neurological Health

Neurodegeneration, Stroke

Stabilizes Blood-Brain Barrier (BBB); provides neuroprotection against oxidative stress.

Transplant Immunology

Allograft Rejection

Modulates Dendritic Cell (DC) function to promote immune tolerance.

Airway Function

Asthma, COPD

Inhibits smooth muscle cell hyper-proliferation and airway remodeling.

Storage and Handling

Vasoactive Intestinal Peptide (VIP) is provided in a highly stable lyophilized (freeze-dried) state. Strict adherence to the following storage and handling protocols is essential to preserve the peptide's structural integrity and ensure the accuracy of all research applications.

Storage Instructions

The lyophilized VIP powder is a stable, crystalline solid.

• Short-Term Storage (Up to 4 Months): Store the lyophilized peptide in a refrigerator at a temperature below 4°C (39°F).
• Long-Term Storage (Multi-Year): For optimal preservation over extended periods, the lyophilized peptide must be stored in a laboratory-grade freezer at -80°C (-112°F).
• After Reconstitution: Once dissolved in an appropriate sterile solvent (e.g., bacteriostatic water), the solution must be stored under refrigeration below 4°C (39°F) and used within 30 days.

Best Practices For Storing Peptides

• Aliquotting: To prevent the primary cause of peptide degradation—repeated freeze-thaw cycles—it is mandatory to divide the entire peptide quantity (both lyophilized and in solution) into small, single-use aliquots immediately upon receipt.
• Freezer Selection: Avoid all self-defrosting (frost-free) freezers for long-term storage, as their temperature variations compromise peptide stability. Use a static deep freezer.
• Environmental Control: Always store peptides in a cold, dry, and dark environment to protect them from light-induced and thermal degradation.

Preventing Oxidation and Moisture Contamination

VIP's stability is critically dependent on protection from atmospheric moisture and oxygen.

• Condensation Prevention: To prevent moisture contamination from condensation (dew/frost), the peptide vial must be allowed to reach room temperature before opening, especially after removal from the freezer.
• Air Minimization: Minimize the time the vial is open. For the long-term stability of the lyophilized powder, the unused portion should be backfilled with an inert gas (such as Argon or Nitrogen) and tightly sealed.

Storing Peptides In Solution

Peptides stored in solution have a substantially reduced shelf life and are more vulnerable to chemical degradation and microbial growth than the lyophilized form.

• Buffer Selection: If solution storage is absolutely required, use sterile buffers with a mild, slightly acidic pH (recommended pH 5-6).
• Freezing Solution: Solutions must be aliquoted and frozen at -20°C or -80°C for any storage period extending beyond 30 days.

Reference Citations

Said SI, Mutt V. Polypeptide with broad biological activity: isolation from small intestine. Science. 1970;169(3951):1217–1218.

Laburthe M, Couvineau A. Molecular pharmacology and structure of VPAC receptors for VIP and PACAP. Regul Pept. 2002;108(2-3):165-173.

Ganea D, Delgado M. The neuropeptides VIP/PACAP and T cells: inhibitors or activators? Curr Pharm Des. 2003;9(12):997-1004.

Harmar AJ, et al. Pharmacology and functions of receptors for VIP and PACAP. Br J Pharmacol. 2012;166(1):4-17.

Vaudry D, et al. Pituitary adenylate cyclase-activating polypeptide and VIP: neuroprotective peptides. Trends Neurosci. 2009;32(12):728-735.

Delgado M, et al. Vasoactive intestinal peptide and the immune system. Endocr Rev. 2004;25(5): 649-685.

Said SI. Vasoactive intestinal peptide in the lung. Ann NY Acad Sci. 1991;629:158-172.

Groneberg DA, et al. Role of VIP in airway smooth muscle function. Eur J Pharmacol. 2001;424(1):21-29.

Gozes I, et al. Neuroprotective peptide activity of VIP and derivatives. J Mol Neurosci. 2003;20(3):273-285.

Martinez C, et al. VIP and immune tolerance in inflammatory bowel disease models. Gut. 1999;45(5): 672-678.