Vasoactive Intestinal Peptide (VIP)
VIP is widely distributed in the enteric and central nervous systems and in peripheral tissues, signalling via VPAC1 and VPAC2 receptors to regulate vascular tone, smooth-muscle relaxation, epithelial secretion and immune responses. It has been investigated in gastrointestinal motility and secretion disorders, pulmonary and vascular diseases, inflammatory and autoimmune conditions, and as a neuro-immune modulator with niche therapeutic potential.
Research areas & putative benefits
Where VIP is used to probe vascular, GI and immune biology.
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>Regulation of intestinal motility, secretion and blood flow in GI physiology and pathophysiology.
>Pulmonary vascular tone and airway smooth-muscle relaxation in respiratory and pulmonary hypertension models.
>Immune regulation and anti-inflammatory signalling in autoimmune and inflammatory disease models.
>Circadian rhythm and central nervous system functions via hypothalamic and cortical VIP-expressing neurons.
Mechanism stack
VIP receptor biology and downstream signalling themes.
VIP primarily signals through VPAC1 and VPAC2 G protein–coupled receptors, which are coupled to Gs and stimulate adenylyl cyclase, increasing cAMP and driving smooth-muscle relaxation, secretion and gene transcription across target tissues.
In blood vessels, VIP induces potent vasodilation and increases mucosal blood flow, particularly in the gastrointestinal tract, contributing to nutrient absorption, mucosal defence and regulation of systemic vascular resistance.
VIP promotes relaxation of GI smooth muscle and sphincters, stimulates intestinal and pancreatic secretion and modulates gastric acid output, shaping coordinated motility and digestive functions under enteric nervous system control.
VIP modulates innate and adaptive immune responses by acting on VPAC1/2 on T cells and innate cells, shifting T helper responses away from Th1/Th17 toward Th2 and regulatory phenotypes and dampening NF‑κB–driven pro-inflammatory cytokine production.
Evidence snapshot
Evidence themes from VIP physiology and translational studies.
| Model / context | Observation | Relevance |
|---|---|---|
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GI physiology and pathophysiology
Foundational
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VIP regulates ion secretion, nutrient absorption, motility and mucosal blood flow; genetic or pharmacologic disruption alters gut homeostasis and contributes to disease phenotypes. | Confirms VIP as a key integrator of neuronal, epithelial and vascular signalling in the gut. |
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Immune and inflammatory models
Neuro-immune
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VIP maintains gut immune tolerance by regulating T-cell responses and Toll-like receptor–mediated innate responses, suppressing Th1/Th17 while promoting Th2 and regulatory T cells and reducing pro-inflammatory cytokines. | Supports the concept of VIP as an endogenous anti-inflammatory and tolerogenic neuropeptide. |
|
Enteric infection and ILC3 recruitment
Host defence
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In murine models, VIP signalling promotes recruitment of group 3 innate lymphoid cells to the gut, maintains IL‑22 production and protects against enteric pathogens; VIP or VPAC1 deficiency leads to susceptibility that can be partly rescued by IL‑22 or ILC3 transfer. | Demonstrates that VIP coordinates neuro-immune–epithelial crosstalk critical for mucosal defence. |
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VPAC receptor pharmacology and CNS models
Receptor / neuroprotection
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VPAC1 and VPAC2 receptors mediate most known VIP effects; VIP and VPAC2-selective agonists show neuroprotective and anti-inflammatory effects in CNS and neonatal brain injury models. | Highlights opportunities to target specific VPAC subtypes or develop VIP analogues with improved selectivity and stability. |
Risk frame & unknowns
Constraints when using VIP as a research or therapeutic agent.
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>Short plasma half-life and systemic vasodilatory effects complicate dosing, requiring careful titration and delivery strategies.
>Excessive vasodilation or hypotension is a potential risk with systemic VIP exposure or high infusion rates.
>Immune-suppressive or tolerance-inducing actions may be undesirable in some infection or cancer contexts if not precisely timed.
>Most therapeutic development focuses on VIP analogues or targeted VPAC agonists to separate beneficial from unwanted systemic effects.
This dossier summarizes mechanistic, preclinical and translational findings on VIP for scientific and educational purposes only. It does not provide medical advice, treatment guidance or dosing recommendations.