Vasoactive Intestinal Peptide (VIP) is a 28-amino acid neuropeptide that functions as a potent vasodilator, immunomodulator, and neurotransmitter. It was first discovered in 1970 by Said and Mutt during the purification of secretin from porcine intestine. VIP is widely distributed in the central and peripheral nervous systems, the gastrointestinal tract, and the respiratory and urogenital systems, playing a crucial role in non-adrenergic, non-cholinergic neurotransmission. Its significance lies in its pleiotropic effects, influencing smooth muscle relaxation, exocrine and endocrine secretion, blood flow, and immune cell activity, making it a key peptide in neuroimmunoendocrinology.
Quick Facts
| Also Known As | VIP, Vasoactive Intestinal Polypeptide |
|---|---|
| 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 |
| Molecular Formula | C147H237N43O43S |
| Molecular Weight | 3326.8 Da |
| PubChem CID | 53314964 |
Research Parameters
| Half-Life | ~1-2 minutes in plasma |
|---|---|
| Stability | Lyophilized powder is stable for at least 24 months when stored at -20°C. After reconstitution in aqueous buffer, it is stable for up to 7 days at 2-8°C if sterile techniques are used, but immediate use is recommended due to rapid degradation. |
| Solubility | Recommended reconstitution in sterile 0.9% saline or bacteriostatic water. Soluble in aqueous buffers at neutral pH. |
| Vial Size | 1 mg |
| Storage (Lyophilized) | -20°C, protect from light and moisture |
| Storage (Reconstituted) | 2-8°C for short-term storage (up to 7 days). For long-term storage, aliquot and freeze at -20°C or below, avoiding repeated freeze-thaw cycles. |
| Typical Research Dose | Research doses vary; common rodent doses are in the range of 10-100 mcg/kg. |
| Cycle Parameters | Research protocols are highly variable and disease model-dependent. Common approaches include daily subcutaneous or intraperitoneal injection for 7-14 days in chronic inflammation models, or single acute administration for physiological studies. |
| Amino Acid Count | 28 |
Mechanism of Action
VIP exerts its effects primarily by binding to and activating two G-protein-coupled receptors, VPAC1 and VPAC2, which are coupled to Gs proteins. This leads to the activation of adenylate cyclase, increased intracellular cyclic AMP (cAMP) levels, and subsequent activation of protein kinase A (PKA). The downstream effects are diverse and tissue-specific.
VPAC1/VPAC2 Receptor Activation: Binding of VIP to its receptors stimulates adenylate cyclase, elevating cAMP. This is a primary signaling pathway mediating smooth muscle relaxation, inhibition of immune cell proliferation, and modulation of neurotransmitter release.
Anti-inflammatory and Immunomodulatory Pathways: VIP downregulates the production of pro-inflammatory cytokines (e.g., TNF-α, IL-6, IL-12) from macrophages and dendritic cells while promoting the secretion of anti-inflammatory cytokines (e.g., IL-10). It can shift T-cell responses from a Th1 to a Th2 profile and promote the generation of regulatory T cells (Tregs).
Vasodilation and Smooth Muscle Relaxation: In vascular and non-vascular smooth muscle, VIP-induced cAMP and PKA activation leads to decreased intracellular calcium, resulting in relaxation and vasodilation. This effect is prominent in cerebral, pulmonary, and coronary vessels.
Neurotrophic and Neuroprotective Effects: In the central nervous system, VIP can act as a neurotrophic factor, promoting neuronal survival and differentiation. It may also modulate synaptic plasticity and protect against excitotoxicity through cAMP/PKA and MAPK pathway activation.
Research Applications
Immunology and Autoimmunity: Research indicates VIP has potent anti-inflammatory and immunomodulatory properties. In animal models of autoimmune diseases such as rheumatoid arthritis, multiple sclerosis, and Crohn's disease, VIP administration reduces disease severity by suppressing pro-inflammatory cytokines, inhibiting T-cell proliferation, and promoting Treg activity.
Pulmonary Research: VIP is a bronchodilator and pulmonary vasodilator. Studies explore its potential in conditions like pulmonary arterial hypertension and asthma, where it can reduce pulmonary vascular resistance and airway constriction. Its role in modulating inflammation in the lung is also a key research area.
Neuroprotection and CNS Disorders: Preclinical research investigates VIP's role in neuroprotection, neurogenesis, and the modulation of circadian rhythms. Its potential in models of stroke, Parkinson's disease, and Alzheimer's disease is being explored due to its ability to reduce neuronal apoptosis and inflammatory glial activation.
Gastrointestinal Physiology: Given its discovery in the gut, VIP is studied for its role in gastrointestinal motility, secretion, and blood flow. Research examines its involvement in conditions like irritable bowel syndrome and its function as a non-adrenergic, non-cholinergic inhibitory neurotransmitter.
Safety & Side Effects
In animal studies, VIP is generally well-tolerated at research doses. Reported side effects are primarily related to its potent vasodilatory action and can include transient hypotension, facial flushing, and tachycardia. Anecdotal reports from early human studies (now historical) noted these cardiovascular effects. Theoretical concerns include excessive immunosuppression at high doses or interference with normal immune surveillance. Its short half-life in circulation limits prolonged systemic effects.
Dosage Information
Disclaimer: The following information is derived from preclinical research studies only and is not for human therapeutic use.
Typical research doses in animal models vary widely. In rodent studies, doses often range from 1 to 50 nmol/kg (approximately 3.3 to 166 mcg/kg) administered via intraperitoneal, subcutaneous, or intravenous injection. Administration is frequently acute or over short periods (days) to study specific physiological responses. Continuous infusion via osmotic minipumps is also used in some chronic models. The frequency is typically once or twice daily.
References
Said SI, Mutt V. Polypeptide with broad biological activity: isolation from small intestine. Science. 1970.
Gomariz RP, et al. VIP in immunity: a neuropeptide with immunomodulatory activity. Ann N Y Acad Sci. 2006.
Delgado M, et al. Vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) as modulators of both innate and adaptive immunity. Crit Rev Oral Biol Med. 2002.
Said SI. Vasoactive intestinal peptide and pulmonary hypertension. Pulm Pharmacol Ther. 2006.
Brenneman DE, et al. Vasoactive intestinal peptide: a neurotrophic releasing agent and an astroglial mitogen. J Neurosci Res. 1990.
Moody TW, et al. VIP and cancer. Peptides. -2007.
Iwasaki M, et al. Structural requirements for vasoactive intestinal peptide (VIP) in its vasodilatory activity. Peptides. 1995.