What Is VIP?
Quick Answer
Vasoactive Intestinal Peptide (VIP) is a 28-amino acid signaling neuropeptide belonging to the glucagon-secretin superfamily. [1] It is a highly conserved molecule across mammalian evolution, identical in humans, pigs, rats, and cows. VIP was originally isolated from the porcine duodenum by Sami I. ...
Vasoactive Intestinal Peptide (VIP) is a 28-amino acid signaling neuropeptide belonging to the glucagon-secretin superfamily. [1] It is a highly conserved molecule across mammalian evolution, identical in humans, pigs, rats, and cows. VIP was originally isolated from the porcine duodenum by Sami I. Said and Viktor Mutt in 1970 at the Medical College of Virginia and Karolinska Institute, respectively. [2]
VIP is derived from a larger precursor molecule, prepro-VIP (170 amino acids), encoded by the VIP gene on chromosome 6 in humans. Prepro-VIP is processed into pro-VIP (149 amino acids), which is further cleaved and amidated by peptidylglycine alpha-amidating monooxygenase to produce the mature, C-terminally amidated 28-amino acid peptide. [6]
VIP is widely distributed in the central and peripheral nervous systems and is produced by neurons, endocrine cells, and immune cells (B-lymphocytes and T-lymphocytes). It exerts potent anti-inflammatory, immunomodulatory, and vasodilatory properties. [3]
The synthetic form, Aviptadil (also known as RLF-100 or Zyesami), has received FDA Orphan compound Designation for the investigation of ARDS, pulmonary hypertension, and sarcoidosis, and Fast Track Designation for critical COVID-19 with respiratory failure. The EMA has granted Orphan compound Designation for ARDS and sarcoidosis. In India, the CDSCO approved Aviptadil for emergency use in COVID-19 ARDS in 2022. [4]
VIP has an extremely short serum half-life of approximately 1–2 minutes, due to rapid degradation by dipeptidyl peptidase-4 (DPP-4) and other serum peptidases. This lability presents significant pharmacological challenges and has driven research into advanced delivery systems including sterically stabilized micelles (SSM), liposomes, and inhalation formulations. [5]
VIP shares 68% homology with PACAP-27 and is reported to be 100-fold more potent than isoproterenol as a bronchodilator and 50-fold more potent than prostacyclin at relaxing pulmonary arteries. [7]
References
- Said SI, Mutt V. Polypeptide with broad biological activity: isolation from small intestine. Science, 169(3951), 1217–1218, 1970.
- Said SI, Rosenberg RN. Vasoactive intestinal polypeptide: abundant immunoreactivity in neuronal cell lines and normal nervous tissues. Science, 192(4242), 907–908, 1976.
- Langer I, Jeandriens J, Couvineau A, et al. Signal transduction by VIP and PACAP receptors. Biochem Soc Trans, 50(1), 2022.
- Youssef JG, Lavin P, Schoenfeld DA, et al. The Use of IV Vasoactive Intestinal Peptide (Aviptadil) in study subjects With Critical COVID-19 Respiratory Failure. Crit Care Med, 50(11), 1545–1554, 2022.
- Domschke S, Domschke W, Bloom SR, et al. Vasoactive intestinal peptide in man: pharmacokinetics, metabolic and circulatory effects. Gut, 19(11), 1049–1053, 1978.
- Harmar AJ, Arimura A, Gozes I, et al. International union of pharmacology. XVIII. Nomenclature of receptors for vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Pharmacol Rev, 50(2), 265–270, 1998.
- Leuchte HH, Baezner C, Baumgartner RA, et al. Inhalation of vasoactive intestinal peptide in pulmonary hypertension. Eur Respir J, 32(5), 1289–1294, 2008.
- Delgado M, Pozo D, Ganea D. The significance of vasoactive intestinal peptide in immunomodulation. Pharmacol Rev, 56(2), 249–290, 2004.
- Couvineau A, Laburthe M. VPAC receptors: structure, molecular pharmacology and interaction with accessory proteins. Br J Pharmacol, 166(1), 42–50, 2012.
- Hou X, Yang H, Bhatt VR, et al. VIP/VPAC signaling in pancreatic islet β-cells and glucose homeostasis. J Mol Endocrinol, 68(3), R65–R75, 2022.
- Smalley SG, Barrow PA, Foster N. Immunomodulation of innate immune responses by vasoactive intestinal peptide (VIP): its experimental potential in inflammatory disease. Clin Exp Immunol, 157(2), 225–234, 2009.
- Constantin S, Bhattarai JP, Bhatt R, et al. VIP signaling in GnRH neurons involves dual Gs/AC and Gq/PLC pathways. J Neuroendocrinol, 36(4), e13392, 2024.
- Hou X, et al. VIP/VPAC signaling in pancreatic islet β-cells: PKA and Epac pathways drive glucose-dependent insulin secretion. J Mol Endocrinol, 2022.
- Moody TW, Nuche-Berenguer B, Jensen RT. Vasoactive intestinal peptide/pituitary adenylate cyclase activating polypeptide, and their receptors and cancer. Curr Opin Endocrinol Diabetes Obes, 23(1), 38–47, 2016.
- Mathioudakis AG, Chatzimavridou-Grigoriadou V, Evangelopoulou E, Mathioudakis GA. Vasoactive Intestinal Peptide Inhaled Agonists: Potential Role in Respiratory Therapeutics. Hippokratia, 17(1), 12–16, 2013.
- Kudo T, Tahara Y, Gamble KL, et al. Vasoactive intestinal peptide produces long-lasting changes in neural activity in the suprachiasmatic nucleus. J Neurophysiol, 110(5), 1097–1106, 2013.
- Said SI. Vasoactive intestinal peptide in the lung. Ann N Y Acad Sci, 527, 450–464, 1988.
- An S, Tsai C, Bhatt R, et al. Vasoactive intestinal polypeptide phase-shifts the circadian clock via cAMP/PKA dependent pathway. J Biol Rhythms, 26(4), 313–326, 2011.
- Mosley RL, Lu Y, Olson KE, et al. A Synthetic Agonist to Vasoactive Intestinal Peptide Receptor-2 Induces Regulatory T Cell Neuroprotective Activities in Models of Parkinson’s Disease. Front Cell Neurosci, 13, 421, 2019.
- Brown SM, Barkauskas CE, Grund B, et al. Intravenous aviptadil and remdesivir for investigation of COVID-19-associated hypoxaemic respiratory failure (TESICO). Lancet Respir Med, 11(9), 791–803, 2023.
- Delgado M, Ganea D. Neuroprotective effect of vasoactive intestinal peptide (VIP) in a mouse model of Parkinson’s disease by blocking microglial activation. FASEB J, 17(8), 944–946, 2003.
- Jayawardena D, Guzman G, Gill RK, et al. Expression and localization of VPAC1, the major receptor of vasoactive intestinal peptide along the length of the intestine. Am J Physiol Gastrointest Liver Physiol, 313(1), G16–G25, 2017.
- Virgolini I, Raderer M, Kurtaran A, et al. Vasoactive intestinal peptide-receptor imaging for the localization of intestinal adenocarcinomas and endocrine tumors. N Engl J Med, 331, 1116–1121, 1994.
- Zhang K, Aruva MR, Shanthly N, et al. PET imaging of VPAC1 expression in experimental and spontaneous prostate cancer. J Nucl Med, 49(1), 112–121, 2008.
- Prasse A, Zissel G, Lützen N, et al. Inhaled vasoactive intestinal peptide exerts immunoregulatory effects in sarcoidosis. Am J Respir Crit Care Med, 182(4), 540–548, 2010.
- Youssef JG, Said SI, et al. Rapid clinical recovery from critical COVID-19 with respiratory failure in a lung transplant patient treated with intravenous vasoactive intestinal peptide. Preprints, 2020.
- Esendagli D, Sarı N, Akhan S, et al. Inhaled Aviptadil Is a New Hope for Recovery of Lung Damage due to COVID-19. Med Princ Pract, 34(2), 191–200, 2025.
- Dewan B, Shinde S. Aviptadil in acute respiratory distress syndrome associated with covid-19 infection. Eur J Pharm Med Res, 9(6), 243–253, 2022.
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