Overview
Vasoactive intestinal peptide (VIP) is a 28-amino-acid neuropeptide first isolated in 1970 by Sami Said and Viktor Mutt from porcine small intestine, after Said had detected a potent vasodilator activity in lung extracts. It is a member of the secretin/glucagon superfamily and shares considerable structural similarity with PACAP, with which it shares two receptors.
VIP is widely distributed in the central and peripheral nervous systems. In the gut it is a major inhibitory neurotransmitter of the enteric nervous system, relaxing smooth muscle and stimulating water and electrolyte secretion. VIP-producing tumours, or VIPomas, cause a syndrome of watery diarrhoea and hypokalaemia that illustrates these secretory actions. In the brain, VIP neurons in the suprachiasmatic nucleus synchronise circadian rhythms, and VIP also influences immune cells. VIP is not approved by the FDA or EMA; its synthetic form, aviptadil, has been investigated in several clinical settings, including respiratory failure. It is used in research on secretion, vasodilation, neuroimmune signalling and VPAC receptor pharmacology.
Mechanism studied
- VIP
- VPAC1 / VPAC2
- cAMP signalling
- Secretion & vasodilation
VIP activates VPAC1 and VPAC2, class B G protein-coupled receptors that also respond to PACAP; it has much lower affinity for the PACAP-selective PAC1 receptor. Both VPAC receptors couple primarily to Gs, increasing cAMP and activating protein kinase A. In intestinal epithelium, this opens CFTR chloride channels and drives fluid secretion. In vascular and visceral smooth muscle, cAMP signalling, together with nitric oxide pathways in some tissues, produces relaxation and vasodilation. In immune cells, VIP signalling generally shifts cytokine profiles toward anti-inflammatory patterns and supports regulatory T-cell function in experimental models. VIP has a very short plasma half-life, limiting systemic studies.
Research highlights
- 01Isolated in 1970 by Said and Mutt, following discovery of vasodilator activity in lung tissue.
- 02VIPoma, or Verner-Morrison syndrome, provided early human evidence of VIP's intestinal secretory actions.
- 03VIP neurons in the suprachiasmatic nucleus are essential for synchronising circadian clock cells in rodent models.
- 04Aviptadil has been studied in respiratory failure and other settings, with mixed and debated results.
- 05Open questions include achieving VPAC receptor selectivity and overcoming the peptide's rapid degradation.
Research areas
- Intestinal secretion research
- Vasodilation studies
- Neuroimmune signalling
- VPAC receptor pharmacology
Evidence & regulatory status
Overall status: Not approved — research (analogues under study)
Key references
- [1]Said, 2008 — Ann N Y Acad Sci
- [2]PubMed — reviews on VIP and intestinal physiology
Latest published research
28,091 papers on PubMed →ATR-FTIR spectral fingerprinting and Chemometric classification of Labisia pumila varieties with exploratory screening of herbal products
Ibrahim IS et al. · Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy · 2027 Feb 5 · PMID 42810031
Mechanism and active ingredients of Gancao Qinlian Granules in ameliorating ulcerative colitis:integrated in vivo, in vitro, network pharmacology and untargeted metabolomics investigation
Liao G et al. · Journal of ethnopharmacology · 2027 Jan 30 · PMID 42542265
Xiongzhi Qufeng Zhitong Granule alleviates nitroglycerin-induced migraine-like nociception and central neuroinflammation by regulating the HMGB1 / TRPV1 / MAPK signaling axis
Huang L et al. · Journal of ethnopharmacology · 2027 Jan 10 · PMID 42398658
Binary classification of sake acidity using excitation-emission matrix fluorescence spectroscopy combined with multivariate analysis models
Moolkaew P et al. · Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy · 2027 Jan 5 · PMID 42647998
Machine learning-guided spectral fingerprinting reveals Parkinson's disease-associated biochemical changes in Drosophila melanogaster
Rathor P et al. · Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy · 2027 Jan 5 · PMID 42585923
Effects of exercise on metabolic risk, cardiovascular fitness, and body composition in elderly women of the past decade: a systematic review and meta-analysis
Shen J et al. · Journal of the International Society of Sports Nutrition · 2026 Dec 31 · PMID 42228407
Increasing plant protein sources in the diet modulates gut microbiota and tryptophan metabolism in men at cardiometabolic risk
Lépine G et al. · Gut microbes · 2026 Dec 31 · PMID 42199008
Blautia coccoides-derived metabolite trimethylamine-N-oxide exacerbates Alzheimer's disease progression via targeting HIF1α signaling
Lv X et al. · Gut microbes · 2026 Dec 31 · PMID 41459734
Live feed from PubMed (NCBI) for “VIP (Vasoactive Intestinal Peptide)”, updated 2026-10-30. Listing a paper is not an endorsement of its findings.
Registered studies
128 on ClinicalTrials.gov →- Not yet recruiting
Developing Virtual Reality Programs to Address Social Skills Deficits in Youth With ADHD
NCT07882823 · Indiana University · 2026-11-01
- Terminated
IBIS Megastudy- Pilot
NCT06785103 · University of California, San Francisco · 2025-03-27
- RecruitingPhase 1
A Study of PT0253 in Participants With KRAS G12D Mutated Advanced Solid Tumors
NCT06797336 · PAQ Therapeutics, Inc. · 2024-12-19
- Completed
Creating VIP Corps to Reduce Maternal Deaths
NCT06089109 · Ann Coker · 2023-09-25
- Recruiting
The Volunteering-in-Place Program for Apathetic Assisted Living Residents With ADRD
NCT06735950 · University of Maryland, Baltimore · 2026-10-01
- Recruiting
Volatility in Paranoia (VIP) Trial: An RCT of Changes in Volatility With Psychotherapy
NCT06835556 · Vanderbilt University Medical Center · 2025-01-15
- Not yet recruiting
Biological Profiles of Neuropeptides, Neurotrophins and miRNA in Migraine
NCT07832032 · Nordlandssykehuset HF · 2026-09-17
- Not yet recruiting
Radicle HealthTM VIP: A Study Assessing the Impact of Health and Wellness Products on Metabolic Health and Related Health Outcomes
NCT07819110 · Radicle Science · 2026-09-17
From the public ClinicalTrials.gov registry for “VIP (Vasoactive Intestinal Peptide)”, updated 2026-10-30. Shown for research context only; Purity Peptides products are not for human use.
FAQ
VIP and PACAP are closely related and both activate VPAC1 and VPAC2. However, only PACAP binds the PAC1 receptor with high affinity. This difference lets researchers use the two peptides together to separate PAC1-mediated effects from VPAC-mediated effects.
A VIPoma is a rare neuroendocrine tumour, usually pancreatic, that secretes excess VIP. The resulting syndrome of profuse watery diarrhoea, low potassium and low gastric acid, sometimes called WDHA or Verner-Morrison syndrome, highlights VIP's powerful effects on intestinal secretion.
Aviptadil is the name given to synthetic VIP. It has been investigated in clinical research, including studies in acute respiratory failure and pulmonary conditions. It is not approved by the FDA or EMA and remains an investigational designation of the native peptide.
Last updated October 2026 · Reviewed by the Purity Peptides research team · Information is a summary of published literature and is not a recommendation for any use.
