VIP 5mg

VIP or vasoactive intestinal peptide is a short peptide hormone containing 28 amino acids, naturally found in both central and peripheral nervous systems. Researchers believe this peptide's wide distribution indicates its diverse potential as a neurotransmitter, immune regulator, vasodilator, and secretagogue. 

It is believed that VIP binds three types of G protein-coupled receptors: PAC1, VPAC1, and VPAC2. Before binding with these receptors, a key regulatory enzyme might be activated, potentially causing biological activity. 

The main difference between these three peptides is their location. Clinical trials indicate that VPAC1 is mainly found in brain and peripheral areas, such as immune cells, intestine, lungs, and liver, while VPAC2 is located in the central nervous system and other peripheral areas, such as reproductive and gastrointestinal tract, skeletal muscles, kidney, heart, and pancreas. Finally, PAC1 is predominant in the adrenal region and brain.

Chemical Structure

• Molecular Formula: C147H237N43O43S
• Molecular Weight: 3326.8 g/mol
• Other Known Titles: PHM27, Vasoactive intestinal polypeptide

Research and Clinical Studies

VIP and Inflammation 

Clinical trials have indicated that VIP, which immune cells seem to produce, shows various potential immunological actions to keep the immune system stable. A couple of studies showed that VIP has anti-inflammatory potential in innate and adaptive immunity.  

When it comes to innate immunity, VIP has been inhibiting responses of inflammatory Th1-type cells and might promote Th2-type cell responses. VIP peptide might decrease inflammation and boost intestinal immunity because of its potential to minimize Th1-type inflammatory cell actions. 

One study has explored the potential connection between inflammation and VIP within the context of NEC or necrotizing enterocolitis, primarily using rodents. VIP, praised for its anti-inflammatory properties, may manage intestinal epithelial barrier integrity and homeostasis. 

All of this may indicate that VIP peptide may have a role in moderating inflammatory responses. Moreover, clinical trials suggest that VIP might preserve tight junction integrity. 

VIP and blood-brain barrier 

The blood-spinal and blood-brain barriers are two crucial parts of the nervous system, protecting the central nervous system's tissue cells and blood vessels. The blood-brain barrier seems to filter everything, from oxygen to nutrition factors, which might affect immunity when they enter these neurological vessels. The compromised blood-brain barrier may cause severe psychological effects. 

Based on some research, VIP peptide may show some neuroprotective potential, which might maintain the blood-brain barrier. This peptide is potentially involved in several functions, such as immune modulation, vasodilation, and neurotransmission. 

By activating AC or adenylate cyclase, VIP peptide may play a crucial role in cAMP or cyclic adenosine monophosphate production. This substance regulates immune response, including those regulatory T cells. 

When these functions are disrupted due to autoimmune reactions against VIP or its receptors, it might potentially lead to enhanced permeability of BSB and BBB, also known as “leakiness,” which might further alleviate autoimmune responses. 

VIP and Cardiac Fibrosis 

Cardiac fibrosis is believed to be highly linked to angiotensinogen-converting enzymes and angiotensinogen receptors, both leading to vascular inflammation. Some clinical trials concluded that VIP peptide could promote the reduction of these angiotensinogen expressions. 

As a result, VIP might help with cardiac fibrosis and reverse heart muscle scarring. These findings are based on the VIP level in the body. Lover doses are linked with higher fibrosis and are almost undetectable in the end-stage of cardiomyopathy. 

To investigate this link further, scientists experimented with VIP, which was administered to mice on a high-salt diet. They recorded changes in myocardial VIP levels, expression of pro-fibrotic mediators, and level of fibrosis through histomorphometry. 

Findings indicate that mice might have higher myocardial VIP levels than controls while having significantly lower fibrosis metrics. However, VIP infusion doesn’t impact all pro-fibrotic mediators. Therefore, a significant reduction in Agt or angiotensinogen and type 1a mRNA expressions was recorded, indicating a possible downregulation of the renin-angiotensin system, a crucial component in fibrotic processes. 

Moreover, while this peptide seems to affect some pro-fibrotic mediators, it did not seem to alter others, such as NFκB, CTGF, TNFα, and TGFβ, indicating that anti-fibrotic properties of this peptide may be selective or mediated via alternative processes. 

VIP and Behavioral Responses in Animals

Clinical trials have indicated that behavior responses in animals may activate VIP neurons. Activating the VIP neurons in the hypothalamus region may also cause the secretion of prolactin hormones, which is believed to trigger behaviors such as aggression, pair bonding, gregariousness, and affiliation. 

VIP peptide seems to be linked to VPAC receptors, which are spread across extrahypothalamic and hypothalamic regions and may affect various reproductive and behavioral functions. Moreover, VIP’s effect on prolactin secretion is connected to different reproductive behaviors across various test subjects since changes in hypothalamus VIP levels closely mimic changes in plasma PRL levels corresponding to various reproductive stages. 

These findings suggest that VIP peptide might shape preparatory behaviors for offspring care. 

One study also explored VIP’s role in social behaviors, suggesting that VIP could impact behaviors such as pair bonding and aggression via its interactions with other neuropeptides, including vasopressin and oxytocin. When it comes to aggression, it is believed that this peptide could potentially affect aggressive behaviors, however, the full role of this peptide is yet to be investigated.  

References:

1. 1. Karen A. Duggan, George Hodge, Juchuan Chen, Tegan Hunter, Vasoactive intestinal peptide infusion reverses existing myocardial fibrosis in the rat, European Journal of Pharmacology, Volume 862, 2019, 172629, ISSN 0014-2999. https://www.sciencedirect.com/science/article/pii/S0014299919305813
   2. Staines DR, Brenu EW, Marshall-Gradisnik S. Postulated vasoactive neuropeptide immunopathology affecting the blood-brain/blood-spinal barrier in certain neuropsychiatric fatigue-related conditions: A role for phosphodiesterase inhibitors in treatment? Neuropsychiatr Dis Treat. 2009;5:81-9. Epub 2009 Apr 8. PMID: 19557103; PMCID: PMC2695238. https://pubmed.ncbi.nlm.nih.gov/19557103/
   3. Chorny A, Gonzalez-Rey E, Delgado M. Regulation of dendritic cell differentiation by vasoactive intestinal peptide: therapeutic applications on autoimmunity and transplantation. Ann N Y Acad Sci. 2006 Nov;1088:187-94. https://pubmed.ncbi.nlm.nih.gov/17192565/
   4. Delgado, M., & Ganea, D. (2013). Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions. Amino acids, 45(1), 25–39. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3883350/
   5. C. Smith, BGR, Aug. 03, 2020. https://bgr.com/2020/08/03/coronavirus-cure-rlf-100-aviptadil-phase-3-trial/ (accessed Jan. 01, 2021).
   6. Welsh, D. K., Takahashi, J. S., & Kay, S. A. (2010). Suprachiasmatic nucleus: cell autonomy and network properties. Annual review of physiology, 72, 551–577. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3758475/
   7. Gonzalez-Rey E, Delgado M. Role of vasoactive intestinal peptide in inflammation and autoimmunity. Curr Opin Investig Drugs. 2005 Nov;6(11):1116-23. https://pubmed.ncbi.nlm.nih.gov/16312132/