VIP — Peptide Protocol Wiki reference

These effects were accompanied by improvements in right ventricular function assessed by echocardiography.

Despite decades of research demonstrating its diverse biological activities and therapeutic potential, VIP has not achieved regulatory approval for any indication.

VIP: Vasoactive Intestinal Peptide Guide | Peptide Protocol Wiki Skip to main content 🧬 Peptide Protocol Wiki Peptides Side Effects New Learn Directory Tools Blog News About ⌘K ⌘K 🌱 New to Peptides?

Start the 7-step beginner guide Peptides Side Effects New Directory Learn Tools Blog News About VIP 📋 Overview 🧬 Molecule 🔄 Similar ⚠️ Side Effects 💉 Dosing 🔬 Research 🚨 Risks 👥 Community 📊 Community Data Home Peptides VIP Neuropeptides Immune Support Vascular & Cardiovascular phase2 VIP Also known as: Vasoactive Intestinal Peptide, VIP Peptide, PHM-27 Research compiled by Peptide Protocol Wiki 📅 Updated January 29, 2026 Citations Verified TL;DR Vasoactive Intestinal Peptide (VIP) is a 28-amino acid neuropeptide belonging to the secretin/glucagon superfamily.

It functions as a neurotransmitter and neuromodulator with diverse roles in vasodilation, smooth muscle relaxation, immune regulation, and circadian rhythm modulation.

Browse all neuropeptide peptides → Table of Contents 📌 TL;DR • Potent vasodilatory and bronchodilatory effects • Neuroprotective properties in multiple models • Anti-inflammatory and immunomodulatory actions • Roles in circadian rhythm and sleep regulation Community-Reported Side Effects Anecdotal ?

nal for pulmonary hypertension and acute respiratory failure 💉 Dosing Amount 50 mcg per spray, 4-8 sprays daily (CIRS/nasal); 50-150 pmol/kg/min (IV infusion) Frequency 4-8 sprays daily divided into 2-4 doses (nasal); continuous 12-hour IV infusion (clinical trials) Duration Ongoing for CIRS protocol (chronic use); 3 days for IV acute respiratory failure protocol Step-wise Titration 💊 Administration Route Intranasal Schedule 4-8 sprays daily divided into 2-4 doses (nasal); continuous 12-hour IV infusion (clinical trials) Timing Intranasal: divided throughout the day; IV: continuous monitored infusion 📅 Cycle Duration Ongoing for CIRS protocol (chronic use); 3 days for IV acute respiratory failure protocol Repeatable Yes Preparation & Storage Diluent: Sterile 0.9% saline ⚗️ Suggested Bloodwork ( 6 tests) CMP When: Baseline Why: Liver and kidney function CBC When: Baseline Why: General health baseline MSH (melanocyte stimulating hormone) When: Baseline Why: Key CIRS biomarker that VIP helps correct TGF-beta 1 When: Baseline Why: Key CIRS inflammatory marker MMP-9 When: Baseline Why: CIRS inflammation marker VEGF When: Baseline Why: VIP modulates vascular endothelial growth factor 💡 Key Considerations → In the Shoemaker protocol, VIP is the last of 11 treatment steps -- patients must meet specific criteria first (passing VCS, clean ERMI 2 or HERTSMI-2 =10, etc.) → Requires continuous hemodynamic monitoring for IV administration →

Contraindication: Avoid in patients with significant hypotension; IV use requires clinical setting with hemodynamic monitoring; intranasal use should follow complete Shoemaker protocol for CIRS Subscribe to unlock this content Get weekly peptide research summaries, new study alerts, and protocol updates — free.

Restore access No thanks, continue reading Related Reading Peptide Kisspeptin reproductive hormone regulating peptide Peptide Alprostadil prostaglandin vasodilator Article Peptides for Gut Health Guide How VIP works at the cellular level Overview of VIP benefits and applications Scientific Details Molecular Formula C147H237N43O43S1 Molecular Weight 3326.8 Da CAS Number 37221-79-7 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 What is VIP?

Originally identified based on its potent vasodilatory properties, VIP has since been recognized as a pleiotropic signaling molecule with far-reaching roles in the nervous system, immune system, gastrointestinal tract, cardiovascular system, and endocrine regulation.

The therapeutic effects were associated with induction of regulatory T cells and tolerogenic dendritic cells in the colonic mucosa.

pituitary adenylate cyclase-activating polypeptide (PACAP), secretin, glucagon, and growth hormone -releasing hormone (GHRH), all of which share structural homology and signal through related class B G-protein coupled receptors.

Both VIP and PHM/PHI are co-released from neurons and exert overlapping but distinct biological effects through shared receptor systems.

Its clinical development has been hampered by its extremely short circulating half-life (approximately 1-2 minutes due to rapid enzymatic degradation), lack of receptor su

btype selectivity, and broad tissue distribution leading to dose-limiting hypotension.

Mechanism of Action # Receptor Signaling: VPAC1 and VPAC2 # VIP exerts its biological effects primarily through two receptor subtypes: VPAC1 (also designated VIPR1) and VPAC2 (VIPR2).

Both are class B (secretin family) G-protein coupled receptors that signal predominantly through Gs-alpha coupling to activate adenylate cyclase, generating intracellular cAMP.

VPAC1 is widely expressed in the lung, liver, gastrointestinal tract, thymus, and brain, and is the dominant VIP receptor on T lymphocytes, macrophages, and dendritic cells.

VPAC2 has a more restricted expression pattern, with high levels in smooth muscle, the suprachiasmatic nucleus, thalamus, pancreatic acinar cells, and mast cells.

VPAC2 also binds both VIP and PACAP, but with somewhat different downstream signaling kinetics.

In addition to the canonical Gs/cAMP pathway, VIP receptor activation can engage secondary signaling cascades depending on the cellular context.

calcium mobilization, particularly through VPAC2 in certain cell types; PI3K/Akt signaling, which mediates some of VIP's anti-apoptotic and neuroprotective effects; and MAPK/ERK pathway activation, contributing to cell proliferation and differentiation responses.

A third receptor, PAC1, binds PACAP with high affinity but VIP with 100-1000 fold lower affinity, and therefore plays a minimal role in VIP signaling at physiological concentrations.

Vasodilation Mechanism # VIP is among the most potent endogenous vasodilators known.

Its vasodilatory action is mediated through both direct smooth muscle relaxation and endothelium-dependent mechanisms.

In vascular smooth muscle, VPAC1/VPAC2 receptor activation increases cAMP, which activates PKA.

PKA phosphorylates myosin light chain kinase (MLCK), reducing its affinity for calcium-calmodulin and thereby inhibiting the contractile machinery.

Neuroprotective Effects # VIP has demonstrated neuroprotective properties across multiple experimental models, including excitotoxicity, oxidative stress, beta-amyloid toxicity, and ischemia-reperfusion injury.

The neuroprotective mechanisms involve several parallel pathways.

Through VPAC receptor activation and cAMP/PKA signaling, VIP upregulates the expression of anti-apoptotic proteins Bcl-2 and Bcl-xL while suppressing pro-apoptotic Bax and caspase-3 activation.

The PAH, COVID-19, and related trials represent the most advanced clinical investigation, but results have been mixed and no regulatory approval has been achieved.

The neuroprotective protein ADNP, whose expression is directly regulated by VIP, has itself been shown to have potent neuroprotective effects and is essential for brain development.

In models of neuroinflammation, VIP reduces microglial activation and production of neu

This anti-neuroinflammatory effect involves suppression of NF-kB signaling in activated microglia and promotion of microglial polarization toward an anti-inflammatory phenotype.

Immune Regulation # VIP acts as a potent anti-inflammatory and immunomodulatory agent, providing a critical interface between the nervous and immune systems.

The mechanisms of immune regulation include several key pathways.

These effects are mediated primarily through VPAC1 and the cAMP/PKA pathway, which phosphorylates and stabilizes IkB-alpha, preventing NF-kB nuclear translocation.

In dendritic cells, VIP inhibits maturation and reduces expression of co-stimulatory molecules and MHC class II, generating tolerogenic DCs that promote regulatory T-cell (Treg) differentiation rather than effector T-cell activation.

In T lymphocytes, VIP promotes the differentiation of Th2 cells while inhibiting Th1 polarization, and enhances the generation and function of CD4+CD25+FoxP3+ regulatory T cells.

Gut-Brain Axis and Circadian Regulation # VIP plays a critical role in the gut-brain axis, serving as both a neurotransmitter in the enteric nervous system and a signaling molecule in the central regulation of gastrointestinal function.