Understanding Vasoactive Intestinal Peptide (VIP)

Vasoactive intestinal peptide, often known as VIP, is a hormone that is found in the gut and was initially recognized as a vasodilator in the year 1970.  Vasoactive intestinal peptide (VIP) is a neuropeptide that performs the tasks of both a neuromodulator and a neurotransmitter. Similar to calcitonin gene-related peptide, it is a powerful vasodilator that controls the activity of smooth muscle, the secretion of epithelial cells, and the flow of blood in the gastrointestinal tract (works as a gastric inhibitory peptide). 

Vasoactive intestinal peptide is a peptide of 28 amino acids and is classified as a member of the secretin/glucagon superfamily. It is a peptide hormone that plays a role in a variety of physiological processes. Vasoactive intestinal peptide (VIP) stimulates the regulation of the relaxation of smooth muscle, intestinal secretion, and hormone release. 

Vasoactive intestinal polypeptide (VIP) shares sequence homology with pituitary adenylyl cyclase-activating peptide (PACAP). Vasoactive intestinal peptide (VIP) is now recognized to have a widespread distribution in both the central nervous system and the peripheral nervous system. Both neurons and immune cells, as well as other types of cells, contain it, and receptors are responsible for its expression.

This 28-amino-acid peptide is a powerful vasodilator. Which means there are a large number of effects of VIP. It calms the blood vessels, and Vasoactive intestinal peptide (VIP) increases the flow of blood through them, demonstrating how VIP acts as a potent vasodilator. Specifically, this is of utmost significance in the gastrointestinal system, where VIP is responsible for enhancing blood flow. Additionally, Vasoactive intestinal peptide (VIP), also known as VIP hormone, is involved in the immunological response and the metabolism of glucose, and it may play a part in disorders such as diabetes and cancer.

Mechanism of Action of Vasoactive Intestinal Peptide

Vasoactive Intestinal Peptide (VIP) has a vasoactive intestinal peptide receptor. VIP and its receptors binding results in a variety of downstream cellular reactions, the most important of which is the activation of the adenylate cyclase-cyclic AMP (cAMP) pathway (that's why we can call it adenylate cyclase-activating peptide), emphasizing the significance of the signal peptide. As a consequence of this activation, a chain of events takes place that affects the relaxation of muscles, the secretion of fluid, and other physiological processes, suggesting that VIP plays a crucial role. 

The G protein-coupled receptor (GPCR) known as VIPR is the receptor that VIP interacts with after it has been activated. Adenylate cyclase is activated as a result of the activation of the Gs protein, which is stimulated by the binding of VIP to VIPR. An enzyme known as adenylate cyclase is responsible for the conversion of ATP to cyclic AMP (cAMP). One of the consequences of VIP-mediated activation of adenylate cyclase is a rapid increase in the amounts of cAMP found within the cell. The activation of protein kinase A (PKA) by cAMP results in the phosphorylation of a large variety of target proteins, which in turn causes a wide range of consequences, including those mediated by cyclase-activating peptide.

This adenylate cyclase-activating polypeptide contributes to its brain regulatory actions, which are predominantly mediated by two receptor subtypes known as VPAC1 and VPAC2. The coupling of these receptors to adenylyl cyclase results in an increase in cAMP and PKA activation, which in turn affects several different intracellular signaling pathways, including those involving peptide histidine. The release of other neurotransmitters, including GABA, is modulated by VIP, which is another way in which VIP modulates neurotransmission.

Vasoactive intestinal polypeptide predominantly functions as an anti-inflammatory drug and is derived from the vip gene. Additionally, it has the ability to perform immunomodulatory effects. VIP accomplishes this by attaching to its receptors, VPAC1 and VPAC2, which are found on a variety of immune cells, such as macrophages, microglia, and T lymphocytes.

Research Evidence

Research on Vasoactive Intestinal Peptide (VIP) reveals that it plays a significant role as a neuromodulator, neurotransmitter, and strong vasodilator. It can also influence a variety of biological activities, such as the motility of the gastrointestinal tract, the immune response, and even social behavior. In addition to its role as a hormone in the gut, VIP also has an effect on the central nervous system and the peripheral nervous system, similar to the actions of peptide histidine isoleucine. Erectile dysfunction, pulmonary hypertension, and inflammatory disorders are some of the conditions that could potentially benefit from the therapeutic applications of VIP, according to the provided evidence.

When VIP is dysregulated, it can lead to clinical symptoms that are largely linked with VIPoma, which is a rare neuroendocrine tumor. The most apparent symptom is secretory diarrhea, which is frequently accompanied by hypokalemia and metabolic acidosis as a result of the excessive loss of fluid and electrolytes throughout the system.

Research Applications

Research on Vasoactive Intestinal Peptide (VIP) encompasses a wide range of areas, such as the role of VIP in the gastrointestinal tract,  pulmonary disorders, and even its possible use as a therapeutic agent for autoimmune diseases, diabetes, and cancer. As a result of its many effects, VIP is currently the topic of inquiry for a wide variety of uses, especially in human vasoactive intestinal polypeptide gene research. VIP is involved in the functioning of the central nervous system, including its participation in the regulation of circadian rhythms and the activity of neurons, highlighting the role of vasoactive intestinal peptide. In conclusion, As a result, it is a subject of current research across a variety of medical specialties.

Several research investigations have compared VIP and secretin regarding the impact that they have on the release of bicarbonate from the pancreas. The partial agonist known as VIP is responsible for stimulating the production of bicarbonate and enhancing one's response to secretin, while also being associated with the release of VIP. The development and optimization of VIP agonists, notably for inhaled delivery, is the primary focus of research. The goal of this research is to increase stability, specificity, and potency of the vip peptide while simultaneously lowering unwanted effects. 

Studies conducted in vitro, in vivo, and clinical trials are all examples of methodologies that are utilized in VIP research. These methodologies frequently involve the utilization of VIP receptor antagonists, agonists, and a variety of drug delivery vehicles.

Future Research Perspectives

When it comes to understanding the role of VIP, future research on VIP promises to bring about breakthroughs that will lead to the development of novel therapeutic techniques. The research will concentrate on elucidating the complex tasks that VIP performs in the brain, as well as its possible uses as a treatment for neurological disorders such as Alzheimer's disease, Parkinson's disease, and autism spectrum disorder, as well as its influence on metabolic conditions such as type 2 diabetes and its receptor VPAC2.

When it comes to the research on VIP, there are certain gaps regarding its role in specific diseases, such as cholera, and the precise placement of its receptor in the gut. Additionally, there are gaps in how it might be used as a therapeutic agent, particularly in disorders such as COVID-19-associated hypoxemia.

References

1. Iwasaki M, Akiba Y, Kaunitz JD. Recent advances in vasoactive intestinal peptide physiology and pathophysiology: focus on the gastrointestinal system. F1000Res. 2019 Sep 12;8:F1000 Faculty Rev-1629. doi: 10.12688/f1000research.18039.1. PMID: 31559013; PMCID: PMC6743256.

2. Delgado M, Ganea D. Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions. Amino Acids. 2013 Jul;45(1):25-39. doi: 10.1007/s00726-011-1184-8. Epub 2011 Dec 3. PMID: 22139413; PMCID: PMC3883350.

3. White CM, Ji S, Cai H, Maudsley S, Martin B. Therapeutic potential of vasoactive intestinal peptide and its receptors in neurological disorders. CNS Neurol Disord Drug Targets. 2010 Nov;9(5):661-6. doi: 10.2174/187152710793361595. PMID: 20632962; PMCID: PMC2967653.

4. Helbing A, Menon G, Sandhu S, et al. VIPoma. [Updated 2025 Feb 23]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2025 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK507698/

5. Gozes, I., & Furman, S. (2004). Potential clinical applications of vasoactive intestinal peptide: A selected update. Best Practice & Research Clinical Endocrinology & Metabolism, 18(4), 623-640. https://doi.org/10.1016/j.beem.2004.08.006

6. Lee WL, Slutsky AS. A negative trial for vasoactive intestinal peptide in COVID-19-associated acute hypoxaemic respiratory failure. Lancet Respir Med. 2023 Sep;11(9):759-760. doi: 10.1016/S2213-2600(23)00218-7. Epub 2023 Jun 19. PMID: 37348523; PMCID: PMC10278994.