VIP (Vasoactive Intestinal Peptide)

VIP (Vasoactive Intestinal Peptide) is a 28-amino acid neuropeptide and neuromodulator found throughout the central and peripheral nervous system, gut, and lungs. Originally identified for its vasodilatory effects, VIP has since become one of the most researched regulatory peptides in immunology, neuroscience, and pulmonary biology. It signals primarily through the VPAC1 and VPAC2 G-protein coupled receptors, activating cyclic AMP (cAMP) cascades that modulate a wide range of physiological functions.

Research Background

VIP was first isolated from porcine small intestine in 1970 and named for its potent vasodilatory activity. Subsequent decades of research revealed its far broader role as a pleiotropic regulatory peptide. It is expressed in neurons, immune cells, and epithelial tissues, and is now recognized as a critical mediator of the gut-brain axis, immune homeostasis, and circadian biology. Its short half-life in circulation (1–2 minutes) has driven interest in stabilized analogs and delivery systems for research purposes.

Areas of Active Research

• Anti-Inflammatory & Immunomodulatory Effects: Among the most well-characterized properties of VIP is its capacity to suppress pro-inflammatory cytokine production. Preclinical models consistently show reduction in TNF-α, IL-6, IL-12, and IFN-γ following VIP administration, alongside promotion of the anti-inflammatory cytokine IL-10 and expansion of regulatory T cells (Tregs). This profile has generated interest in autoimmune and inflammatory disease research.
• Pulmonary & Cardiovascular Research: VIP is a potent pulmonary vasodilator and bronchodilator. Research in models of pulmonary arterial hypertension (PAH) has shown VIP reduces pulmonary vascular resistance and inhibits smooth muscle cell proliferation. Studies have also explored its role in regulating cardiac function and systemic vascular tone via VPAC receptor signaling.
• Neuroprotection & CNS Research: VIP is widely expressed in the brain and has been studied in models of neurodegeneration, traumatic brain injury, and stroke. Preclinical findings suggest VIP promotes neuronal survival, reduces oxidative stress, and modulates neurotransmitter systems including acetylcholine, dopamine, and GABA. It has also been studied in models of Parkinson’s disease and Alzheimer’s-related neuroinflammation.
• Circadian Rhythm & Sleep Regulation: VIP is a key signaling molecule in the suprachiasmatic nucleus (SCN), the brain’s master circadian clock. It synchronizes circadian oscillators between SCN neurons and coordinates light-entrainable rhythms. Research has explored VIP’s involvement in sleep architecture, jet lag models, and shift-work disruption.
• Gastrointestinal Research: As a primary neurotransmitter of the enteric nervous system, VIP regulates intestinal smooth muscle relaxation, secretion, and mucosal blood flow. It has been studied in models of inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and gut barrier integrity. Preclinical IBD models show VIP reduces intestinal inflammation and promotes epithelial repair.
• Chronic Inflammatory Response Syndrome (CIRS) Research: VIP has been investigated as a potential biomarker and therapeutic target in CIRS — a multi-system inflammatory condition associated with biotoxin exposure. Research has documented suppressed endogenous VIP levels in CIRS populations and explored exogenous VIP administration for symptom modulation. This represents an emerging area of translational interest.
• Reproductive & Endocrine Research: VIP has roles in regulating gonadotropin-releasing hormone (GnRH) pulsatility, prolactin secretion, and ovarian function. Preclinical studies have explored VIP in reproductive biology and potential utility in endocrine dysregulation models.
• COVID-19 / ARDS Research: Following 2020, VIP received renewed attention as a potential research tool in cytokine storm and acute respiratory distress syndrome (ARDS) models. Its dual anti-inflammatory and vasodilatory profile positioned it as a compound of interest in severe inflammatory lung injury research.

Mechanism of Action

VIP binds to VPAC1 and VPAC2 receptors (class B GPCRs), both of which couple to adenylate cyclase via Gαs, elevating intracellular cAMP. This downstream signaling cascade activates PKA and EPAC pathways, broadly suppressing NF-κB-mediated inflammatory signaling and modulating T cell differentiation toward a regulatory phenotype. VPAC1 is constitutively expressed across immune cells and gut epithelium; VPAC2 is more inducible and highly expressed in brain and smooth muscle. The distinct tissue distribution of these receptors underpins VIP’s wide-ranging and context-dependent research profile.

Research Notes

• 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 (28 AA)
• Molecular weight: ~3,326 Da
• Half-life: ~1–2 minutes in circulation (enzymatic degradation by NEP and DPP-IV)
• Storage: Lyophilized — store at -20°C; reconstitute with sterile BAC water; stable 4–8 weeks refrigerated post-reconstitution
• Research use only. Not intended for human or veterinary use.

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