What are the potential benefits of Vasoactive Intestinal Peptide?

Potent anti-inflammatory: prevention and treatment of experimental rheumatoid arthritis. Glucose-dependent insulin secretion stimulation without hypoglycemia risk. Smooth muscle relaxation in GI, vascular, and respiratory systems. Suppression of inflammatory cytokines (TNF, IL-1) in synovium. Upregulation of anti-inflammatory IL-10 and IL-1RA. Protection against inflammatory bowel disease. Potential neuroprotective effects via PACAP-related pathways

What compounds work synergistically with Vasoactive Intestinal Peptide?

Vasoactive Intestinal Peptide has been studied alongside PACAP, Anti-inflammatory biologics for potential synergistic effects.

Vasoactive Intestinal Peptide — Mechanism, Benefits, Research & Synergies

Overview

Vasoactive Intestinal Peptide (VIP) is a naturally occurring 28-amino acid neuropeptide found in the nervous system and immune cells throughout the body. It acts as both a neurotransmitter and a hormone with diverse physiological roles including smooth muscle relaxation, vasodilation, regulation of gastrointestinal secretions, and insulin secretion. VIP's immunomodulatory properties, particularly its potent anti-inflammatory effects, have made it a research target for autoimmune and inflammatory diseases, including experimental arthritis and multiple sclerosis.

Mechanism of Action

VIP binds to VPAC1 and VPAC2 receptors (GPCRs), activating adenylyl cyclase and elevating intracellular cAMP levels. In immune cells, this drives reduction of pro-inflammatory cytokines (TNF, IL-1) and upregulation of anti-inflammatory mediators (IL-10, IL-1RA). In pancreatic beta-cells, VPAC2 activation in a glucose-dependent manner stimulates insulin secretion via PKA and Epac signaling, closing ATP-dependent K+ channels and enabling Ca2+ influx. In inflammatory arthritis models, VIP reduces inflammatory infiltrate, pannus formation, cartilage destruction, bone erosion, and lowers CD4:CD8 ratio in synovium.

Potential Benefits

Potent anti-inflammatory: prevention and treatment of experimental rheumatoid arthritis
Glucose-dependent insulin secretion stimulation without hypoglycemia risk
Smooth muscle relaxation in GI, vascular, and respiratory systems
Suppression of inflammatory cytokines (TNF, IL-1) in synovium
Upregulation of anti-inflammatory IL-10 and IL-1RA
Protection against inflammatory bowel disease
Potential neuroprotective effects via PACAP-related pathways

Research Dosage Notes

The following reflects doses used in published research studies. This is not medical advice.

Research doses vary widely by route and model. Half-life is only minutes in plasma, limiting clinical application. VPAC agonist development ongoing.

Amino Acid 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

Side Effects & Safety

Hypotension at high doses (vasodilation effect)
Tachycardia
Flushing
Very short half-life limits clinical utility

Synergistic Compounds

The following compounds have been studied alongside Vasoactive Intestinal Peptide for potential complementary or synergistic effects:

PACAPAnti-inflammatory biologics

Learn More

Beginner's GuideNew to peptides? Start here Stacking GuideSynergistic combinations Administration RoutesSubQ, IM, oral, nasal & more Reconstitution CalculatorCalculate exact dosing Peptides vs SARMsFull comparison How Peptides Are MadeSPPS, purification & QC

References & Further Reading

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Quick Facts

Molecular Weight	3325.8 g/mol
Research Status	Extensive preclinical data. Limited clinical trials for inflammatory conditions. Short half-life limits therapeutic utility. VPAC2-selective analogs under development for diabetes. Not FDA-approved as a peptide drug, though VPAC receptor agonist programs active.

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Vasoactive Intestinal Peptide