VIP (Vasoactive Intestinal Peptide) Research Guide — VPAC1/VPAC2 Mechanism, Neuroimmune Anti-Inflammatory Biology & Research Applications (2026)
- VIP (vasoactive intestinal peptide; also VIP1–28) is a 28-amino acid neuropeptide belonging to the secretin/glucagon superfamily (shared with PACAP, secretin, glucagon, GIP, and GLP-1). It was first isolated from porcine small intestinal tissue in 1970 by Said and Mutt. Despite its name, VIP is now recognized primarily as a pleiotropic neuroimmune signaling peptide with expression throughout the central and peripheral nervous systems, immune cells, and multiple peripheral organs. YPB offers research-grade VIP as VIP10 in a 10mg configuration (Research Use Only).
- Mechanism: VIP activates VPAC1 and VPAC2 receptors — two Class B (secretin family) G protein-coupled receptors (GPCRs) that couple primarily to Gs → adenylyl cyclase → cAMP ↑ → PKA activation. VIP binds both VPAC1 and VPAC2 with similar high affinity (Kd ~1 nM each); VPAC1 is constitutively expressed on lymphocytes and macrophages; VPAC2 is expressed on mast cells, smooth muscle, brain regions, and is upregulated by inflammatory stimuli. Both receptors also activate MAPK/ERK pathways and in some contexts PLC (phospholipase C).
- Anti-inflammatory profile: VIP’s most extensively studied research application is immune modulation. Through VPAC1/2 activation on macrophages, dendritic cells, and T cells: (1) suppresses pro-inflammatory cytokine production (TNF-α, IL-6, IL-12, IFN-γ, IL-17; inhibits COX-2/PGE2 and iNOS/NO); (2) stimulates anti-inflammatory cytokines (IL-10, IL-1Ra); (3) promotes regulatory T cell (Treg) differentiation and function; (4) reduces dendritic cell co-stimulatory molecule expression; (5) inhibits Th1 and Th17 T-cell polarization. These combined effects make VIP one of the most potent endogenous anti-inflammatory neuropeptides.
- Additional research applications: vascular smooth muscle relaxation (vasodilation research); bronchodilation (pulmonary research); circadian rhythm modulation (suprachiasmatic nucleus VPAC2 expression); neuroprotection; gut-brain axis signaling; pulmonary arterial hypertension (PAH; Aviptadil/Zyesami received FDA Fast Track designation for COVID-19 ARDS). Not research-grade for general use. Research Use Only (RUO). Updated April 2026.
What Is VIP and Why Is It a Research Priority in Neuroimmune Biology?
VPAC1/VPAC2 Gs/cAMP Agonist
Pleiotropic Neuroimmune Signaling
VIP was originally named “vasoactive intestinal peptide” to reflect its first characterized actions: potent vasodilation and its initial isolation from intestinal tissue (Said and Mutt, 1970). Updated April 2026. Over the following five decades, research revealed that VIP is far more than an intestinal vasodilator: it is one of the most broadly expressed and functionally diverse neuropeptides in the mammalian body, present in neurons of the central and peripheral nervous systems, released by immune cells including Th2 CD4+ T cells, CD8+ T cells, mast cells, and neutrophils, and acting on virtually every immune cell type through VPAC1 and VPAC2 receptor expression. This neuroimmune distribution — released by neurons into immune tissue and released by immune cells in immune reactions — positions VIP at the intersection of the nervous and immune systems, making it a central research tool for neuroimmunology, autoimmune disease biology, pulmonary physiology, and inflammatory bowel disease research.
Its primary research significance in 2026 is as an endogenous anti-inflammatory neuropeptide pharmacological probe: VIP activates VPAC1/2 to suppress pro-inflammatory cytokine production and promote Treg differentiation in ways that are mechanistically distinct from glucocorticoids, NSAIDs, or biological anti-TNF approaches, making it uniquely valuable for studying the neuropeptide-mediated component of immune regulation.
Key Characteristics
| Parameter | Value |
|---|---|
| Full Name | Vasoactive intestinal peptide; VIP; VIP1–28 |
| Discovery | Said & Mutt (1970); isolated from porcine small intestinal tissue; first characterized as vasodilatory peptide |
| Amino Acids | 28 (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-NH₂); C-terminal amidation present |
| Molecular Weight | ~3,326 Da |
| Superfamily | Secretin/glucagon peptide superfamily; shares 68% homology with PACAP (pituitary adenylyl cyclase-activating polypeptide); related to secretin, glucagon, GIP, GLP-1, GLP-2 |
| Receptors | VPAC1 (VIPR1; Kd ~1 nM; Gs-coupled; constitutively expressed on lymphocytes, macrophages, liver, lung, intestine) and VPAC2 (VIPR2; Kd ~1 nM; Gs-coupled; mast cells, smooth muscle, brain; upregulated by LPS/inflammatory stimuli). VIP does not bind PAC1 (PACAP-preferring; Kd >500 nM for VIP). |
| Downstream Signaling | Gs → adenylyl cyclase → cAMP ↑ → PKA → CREB transcription; also MAPK/ERK; some contexts: PLC/IP3/Ca²⁺ (VPAC2) |
| Primary Anti-Inflammatory Actions | Inhibits: TNF-α, IL-6, IL-12, IFN-γ, IL-17, COX-2/PGE2, iNOS/NO. Stimulates: IL-10, IL-1Ra. Promotes: Treg differentiation; inhibits Th1/Th17 polarization; reduces DC co-stimulatory molecule expression |
| Half-Life | Short (<1 minute in plasma; rapidly degraded by plasma peptidases); C-terminal amidation provides modest stability; research typically uses acute or pulsatile administration |
| YPB Configuration | VIP10 — 10mg configuration |
| FDA Status | Not research-grade for general use. Aviptadil (synthetic VIP; Zyesami) received FDA Fast Track designation for COVID-19 ARDS/respiratory failure. Research Use Only (RUO). |
| WADA Status | Not listed on WADA Prohibited List 2025 |
| Storage | Lyophilized: −20°C. Reconstituted in 0.1% BSA/PBS or sterile water; 2–8°C, use within 14 days. Sensitive to plasma peptidases; short shelf life in serum-containing media without protease inhibitors. |
How Does VIP Signal? VPAC1/VPAC2 Gs/cAMP Cascade
VPAC1 vs. VPAC2: Tissue Distribution and Differential Roles
VIP binds both VPAC1 and VPAC2 with nanomolar affinity (~1 nM Kd for each), but the two receptors have distinct tissue and cellular expression patterns that determine the context-dependence of VIP’s effects. VPAC1 is constitutively expressed on T lymphocytes (including thymocytes, CD4+, CD8+ T cells), macrophages, monocytes, and dendritic cells in resting conditions — making it the primary receptor for VIP’s neuroimmune actions under baseline conditions. VPAC2 is expressed on mast cells (where it is the only VIP receptor), vascular and airway smooth muscle, specific brain regions (thalamus, suprachiasmatic nucleus, hippocampus), and peripheral tissues including pancreas, kidney, and reproductive tract. In immune cells, VPAC2 expression is upregulated by LPS and inflammatory stimuli — suggesting a role in amplifying VIP signaling specifically during active immune responses. The suprachiasmatic nucleus VPAC2 expression is relevant to VIP’s well-characterized role in circadian rhythm regulation.
Gs/cAMP/PKA Signaling Cascade
Both VPAC1 and VPAC2 couple primarily through Gs (stimulatory G protein) to activate adenylyl cyclase, generating cAMP from ATP. Elevated cAMP activates protein kinase A (PKA) and exchange proteins directly activated by cAMP (EPAC/cAMP-GEFs). In immune cells, the cAMP/PKA pathway drives the anti-inflammatory gene expression program: PKA phosphorylates and activates CREB, which drives IL-10 and IL-1Ra transcription while suppressing NF-κB-driven pro-inflammatory cytokine gene expression. This cAMP/PKA-mediated NF-κB suppression is the molecular basis for VIP’s TNF-α, IL-6, and IL-12 inhibitory effects in LPS-stimulated macrophages. The cAMP pathway also mediates smooth muscle relaxation (vasodilation, bronchodilation) by activating cAMP-dependent myosin light chain phosphatase.
What Research Applications Has VIP Been Studied For?
Inflammation and Autoimmune Disease Research
The most extensively published VIP research application is studying its role in innate and adaptive immune regulation. VIP acts on macrophages to inhibit LPS-stimulated production of TNF-α, IL-6, IL-12, and nitric oxide (via iNOS suppression) while stimulating IL-10 production — confirmed across multiple published studies using VPAC1-expressing macrophage and monocyte cell lines. In T-cell biology, VIP inhibits Th1 cell differentiation (reduced IFN-γ production) and Th17 polarization (reduced IL-17) while promoting regulatory T cell (Treg) expansion and function. Published animal model data demonstrate VIP efficacy in collagen-induced arthritis, experimental autoimmune encephalomyelitis (EAE/MS model), inflammatory bowel disease (TNBS colitis), and sepsis models.
Pulmonary Research (Bronchodilation and PAH)
VIP is a potent bronchodilator and pulmonary vasodilator through VPAC1/2 activation on airway and vascular smooth muscle (Gs/cAMP → myosin light chain phosphatase activation → smooth muscle relaxation). Published clinical data: inhaled VIP decreased mean pulmonary artery pressure (MPAP) in pulmonary arterial hypertension (PAH) research subjects in an early clinical study. Aviptadil (synthetic VIP; Zyesami, developed by NeuroRx/Relief Therapeutics) received FDA Fast Track designation and Breakthrough Therapy designation for COVID-19-associated respiratory failure/ARDS, reflecting VIP’s anti-inflammatory and alveolar epithelial protection activities in lung tissue. As of April 2026, Aviptadil is not broadly research-grade.
Circadian Biology Research
VPAC2 is strongly expressed in the suprachiasmatic nucleus (SCN), the master circadian clock in the hypothalamus. VIP release from SCN neurons synchronizes the intrinsic ~24-hour oscillators of individual SCN cells through VPAC2-mediated cAMP signaling. Mice lacking VIP or VPAC2 show severely disrupted circadian wheel-running rhythms, demonstrating that VIP is required for normal circadian entrainment. This makes VIP an essential tool for studying circadian clock mechanisms and SCN coupling biology.
Gastrointestinal and Gut-Brain Axis Research
VIP is produced by enteric nervous system neurons throughout the GI tract, where it regulates intestinal secretion, motility (smooth muscle relaxation), and epithelial barrier function. Gut VIP-expressing neurons are part of the gut-brain axis, and VIP’s anti-inflammatory effects on intestinal macrophages (via VPAC1) make it relevant to inflammatory bowel disease (IBD) research. VIP-deficient mouse models show increased susceptibility to colitis, confirming VIP’s role in maintaining intestinal immune homeostasis.
What Does the Research Data Show?
| Research Area | Model / Evidence | Key Finding & Notes | Year(s) |
|---|---|---|---|
| Macrophage/Innate immune anti-inflammation | In vitro (macrophage, monocyte, DC cell lines and primary cells) | VIP suppresses LPS-induced TNF-α, IL-6, IL-12, NO (via iNOS) and PGE2 (via COX-2); stimulates IL-10 and IL-1Ra via VPAC1/cAMP/PKA. Confirmed in multiple independent groups. Normal cell toxicity not observed at research concentrations. | 1997–present |
| T-cell immunomodulation and Treg promotion | In vitro + in vivo (mouse autoimmune models) | VIP inhibits Th1 (IFN-γ) and Th17 (IL-17) differentiation; promotes Treg expansion and FOXP3 expression; reduces autoimmune pathology in EAE (MS model), collagen-induced arthritis, and TNBS colitis models. Effect mediated through VPAC1/VPAC2 on T cells and DCs. | Various |
| Circadian rhythm biology | Genetic (VIP-null, VPAC2-null mice) | VIP-deficient mice show severely disrupted circadian rhythms; SCN neurons lose synchrony; wheel-running and sleep-wake cycles impaired. VIP is required for normal inter-neuronal SCN coupling. VPAC2-null mice develop exacerbated EAE, linking circadian and immune regulation. | Various |
| Pulmonary/PAH (Aviptadil/Zyesami) | Phase 2/clinical (inhaled VIP in PAH research subjects; IV Aviptadil in COVID-19 ARDS) | Inhaled VIP reduced MPAP in 8 PAH research subjects (NYHA III–IV) in early study. Aviptadil received FDA Fast Track and Breakthrough Therapy designation for COVID-19 ARDS; Phase 2 data showed respiratory improvement in some subgroups. Not broadly research-grade as of April 2026. | 2004–2022 |
How Does VIP Compare to Other Neuroimmune and Anti-Inflammatory Research Peptides?
| Parameter | VIP | KPV | LL-37 | ARA-290 |
|---|---|---|---|---|
| Primary Target | VPAC1/VPAC2 (Gs-coupled GPCRs); class B secretin family receptors; cAMP/PKA anti-inflammatory | MC1R/MC3R (melanocortin receptors); Gq/Gs-coupled; epithelial and immune cells; anti-inflammatory | Toll-like receptors (TLR4, TLR9), EGFR, FPR2; innate immune activation + direct membrane antimicrobial | Innate repair receptor (EPOR/βcR); injury-selective; PI3K/Akt anti-apoptotic + NF-κB suppression |
| Anti-Inflammatory Mechanism | cAMP/PKA → NF-κB suppression; COX-2 and iNOS inhibition; IL-10/IL-1Ra stimulation; Treg promotion | NF-κB inhibition; POMC system; primarily epithelial anti-inflammatory; IBD models | Immunomodulatory + antimicrobial; can be pro- or anti-inflammatory depending on context | Anti-apoptotic; anti-inflammatory via injury-upregulated IRR; neural/organ protection specific |
| Tissue Target Breadth | Broad: immune cells, vascular smooth muscle, airway, CNS (circadian), GI (enteric nervous system), neuroendocrine | Primarily GI epithelium, skin, gut-brain axis | Skin, mucosa, phagocytes; broad AMP spectrum | Injured/inflamed neural and visceral tissue; injury-selective |
| Clinical Context | Aviptadil (FDA Fast Track/Breakthrough designation for COVID-19 ARDS); PAH clinical data; not broadly approved | No clinical trial | No FDA approval; endogenous AMP | FDA orphan designation (sarcoidosis neuropathic pain); Phase 2 T2DM neuropathy |
| Half-Life | Short (<1 min plasma); rapidly degraded by plasma peptidases; acute/pulsatile research administration | Short (tripeptide) | Moderate (37 AA) | Moderate (11 AA; pyroglutamate protection) |
| YPB SKU | VIP10 (10mg) — see product | YPB catalog — see guide | YPB.271 — see guide | YPB catalog — see guide |
VIP is the most functionally broad anti-inflammatory neuropeptide in the YPB catalog, with simultaneous neuroimmune, vascular, pulmonary, and circadian research applications that no single competing compound covers. KPV (see the KPV Research Guide) is the gut epithelial anti-inflammatory complement via the melanocortin axis; LL-37 (see the LL-37 Research Guide) is the innate antimicrobial/immunomodulatory AMP; ARA-290 (see the ARA-290 Research Guide) is the injury-selective EPO-derived neuroprotective anti-inflammatory. Together they cover VPAC neuroimmune (VIP), melanocortin epithelial (KPV), innate AMP (LL-37), and injury-repair EPO (ARA-290) anti-inflammatory mechanisms.
What Should Researchers Know About VIP Stability and Handling?
Short Plasma Half-Life
VIP is rapidly degraded in plasma by non-specific peptidases (primarily endopeptidases and carboxypeptidases). Plasma half-life in vivo is less than one minute. In cell culture systems, serum-containing media (which contains plasma peptidases) degrades VIP within minutes. For sustained VIP receptor activation in cell culture experiments, options include: (1) adding fresh VIP at intervals; (2) using serum-free or low-serum conditions; (3) using protease inhibitor cocktails in the culture medium; or (4) using metabolically stabilized VIP analogs for longer-duration studies. For acute signaling assays (cAMP measurement within 5–15 minutes of VIP addition), this stability limitation is less critical.
C-Terminal Amidation
Native VIP1–28 has a C-terminal amide (-NH₂; Asn-NH₂ at position 28). This C-terminal amidation is required for full receptor binding affinity; a VIP with a free C-terminal carboxylate (Asn-OH at position 28) shows significantly reduced VPAC1/VPAC2 binding. COA verification: MS at ~3,326 Da (amidated form; ~3,327 Da for free acid form). All YPB VIP batches include lot-traceable COA documentation through the COA Library.
Storage
Lyophilized: −20°C for up to 24 months. Reconstituted in 0.1% BSA/PBS to prevent adsorption to container surfaces at low concentrations; 2–8°C, use within 14 days. Prepare single-use aliquots from lyophilized stock to avoid freeze-thaw degradation.
Key Research Findings
- Pleiotropic neuroimmune neuropeptide: Expressed in CNS/PNS neurons AND immune cells (Th2, CD8, mast cells, neutrophils); receptors on virtually all immune cell types (VPAC1 constitutively on T cells/macrophages; VPAC2 on mast cells/smooth muscle/brain).
- VPAC1/VPAC2 Gs/cAMP/PKA mechanism: cAMP → PKA → CREB activation + NF-κB suppression → anti-inflammatory gene program. Both receptors: Kd ~1 nM; VIP does NOT activate PAC1 (Kd >500 nM for VIP; PACAP-preferring).
- Anti-inflammatory cytokine profile: Inhibits TNF-α, IL-6, IL-12, IFN-γ, IL-17, PGE2, NO; stimulates IL-10, IL-1Ra; promotes Treg; inhibits Th1/Th17; reduces DC co-stimulation. Confirmed in macrophages, DCs, T cells.
- Circadian biology: VPAC2 in SCN required for circadian synchronization; VIP-null mice show severely disrupted circadian rhythms; links circadian and immune regulation.
- Pulmonary/Aviptadil context: FDA Fast Track/Breakthrough designation for COVID-19 ARDS (not broadly approved); PAH clinical vasodilation data; bronchodilatory research applications.
- Short plasma half-life (<1 min): Rapid degradation by plasma peptidases; C-terminal amidation required for full receptor affinity; confirm amidation at ~3,326 Da (not 3,327 Da free acid) in COA.
- VIP vs. PACAP distinction: VIP = VPAC1 + VPAC2 only; PACAP = VPAC1 + VPAC2 + PAC1. For VIP-selective research, confirm effects are not PAC1-mediated by comparing to selective VPAC1/VPAC2 agonists.
- Truncated VIP10–28 (not YPB product): A shorter fragment released by mast cells in IgE-stimulated conditions; acts as partial agonist/antagonist at VPAC receptors. YPB VIP10 = full-length VIP1–28 in 10mg configuration, not the VIP10–28 fragment.
Browse the Full Research Catalog
Market Demand and Research Interest
| Demand Indicator | VIP Data Point |
|---|---|
| PubMed publications | 15,000+ (vasoactive intestinal peptide / VIP) |
| Clinical context | Aviptadil (Zyesami) FDA Fast Track + Breakthrough designation (COVID-19 ARDS); PAH inhalation data; IBD and autoimmune models across multiple research groups |
| Unique catalog position | Only VPAC1/VPAC2 agonist in YPB catalog; only secretin/glucagon superfamily peptide specifically for neuroimmune research; circadian biology + immune regulation + vascular biology in a single compound |
| Research communities | Neuroimmunology; autoimmune disease; pulmonary biology; circadian rhythm; IBD/GI; vascular physiology |
| Disease model relevance | EAE/MS; rheumatoid arthritis; IBD; sepsis; PAH; COVID-19 lung biology; T2DM; neurodegenerative disease |
| Keyword difficulty range | Medium (KD 15–30); well-established research audience |
How Can Researchers Offer VIP Under Their Own Brand?
Wholesale Pricing & Margin Analysis
| SKU | Compound | Premier ($497/mo) | Core ($297/mo) | Suggested MSRP | Premier Margin |
|---|---|---|---|---|---|
| VIP10 (RUO) | VIP (Vasoactive Intestinal Peptide; 28 AA) — 10mg | TBC Premier | TBC Core | TBC | TBC at Premier tier |
Contact the YPB team for confirmed Premier and Core tier pricing. Use the YPB Profit Calculator to model projected revenue. White-label brands offering VIP alongside KPV, LL-37, and ARA-290 create the most mechanistically diverse anti-inflammatory research neuropeptide catalog: VPAC1/2 neuroimmune (VIP) + MC1R/3R epithelial (KPV) + TLR/AMP innate (LL-37) + IRR injury-protective (ARA-290) — four non-overlapping mechanisms from a single inflammatory biology buyer audience. Download the full catalog for all neuroimmune category pricing.
Methodology & Data Sources
Methodology & Data Sources
Scientific literature: PubMed searched for “vasoactive intestinal peptide,” “VIP VPAC1 VPAC2,” “VIP anti-inflammatory,” and “VIP neuropeptide immune.” Search conducted through April 2026.
Key sources: Said & Mutt (1970, discovery); Gonzalez-Rey & Delgado (2006) PMC3883350 (neuroimmune VIP review); Fernandez-Martin et al. (1997) J Immunol (VIP IL-10 macrophage data); Ganea et al. (2015) Acta Physiol (Th1/Th17/Treg VIP modulation); PMC3415636 (VPAC receptor structure review); PMC4275378 (VPAC2 EAE); Aviptadil FDA Fast Track context.
Limitations: VIP’s very short plasma half-life (<1 min) limits in vivo research utility compared to stable analogs. Many published VIP studies use supraphysiological concentrations; receptor-selectivity confirmation using VPAC1/VPAC2 selective agonists and antagonists is recommended for mechanistic attribution. Aviptadil clinical development is ongoing; not broadly research-grade as of April 2026. This article is for educational purposes only.
References
- Said, S. I., & Mutt, V. (1970). Polypeptide with broad biological activity: isolation from small intestine. Science, 169(3951), 1217–1218. (VIP discovery.)
- Gonzalez-Rey, E., & Delgado, M. (2006). Vasoactive intestinal peptide: a neuropeptide with pleiotropic immune functions. Cell Mol Life Sci. PMC3883350.
- Fernandez-Martin, A., Gonzalez-Rey, E., Chorny, A., Martin, J., & Delgado, M. (2006). VIP prevents experimental multiple sclerosis by downregulating both inflammatory and autoimmune components of the disease. Ann N Y Acad Sci, 1070, 276–281.
- Gonzalez-Rey, E., Chorny, A., Varela, N., & Delgado, M. (2006). Differential regulation of Toll-like receptor-induced interleukin-12 by endogenous IL-10 and vasoactive intestinal peptide expression in macrophages. Immunology.
- Ganea, D., Hooper, K. M., & Kong, W. (2015). The neuropeptide vasoactive intestinal peptide: direct effects on immune cells and involvement in inflammatory and autoimmune diseases. Acta Physiol, 213(2), 442–452.
- Abad, C., Gomariz, R. P., & Waschek, J. A. (2011). VIP and PACAP receptor agonists: potency and selectivity in immune modulation. Curr Top Med Chem, 11(10), 1217–1229.
- Laburthe, M., & Couvineau, A. (2002). Molecular pharmacology and structure of VPAC receptors for VIP and PACAP. Regul Pept, 108(1–3), 165–173.
- Hökfelt, T., Johansson, O., Ljungdahl, Å., Lundberg, J. M., & Schultzberg, M. (1980). Peptidergic neurones. Nature, 284(5754), 515–521. (VIP nervous system expression.)
- Vaudry, D., Gonzalez, B. J., Basille, M., Yon, L., Fournier, A., & Vaudry, H. (2000). Pituitary adenylate cyclase-activating polypeptide and its receptors: from structure to functions. Pharmacol Rev, 52(2), 269–324. (VIP/PACAP/VPAC receptor context.)
Frequently Asked Questions
VIP (vasoactive intestinal peptide; 28 AA; MW ~3,326 Da; C-terminal amidated; secretin/glucagon superfamily) is an endogenous neuropeptide that activates VPAC1 and VPAC2 receptors (Class B Gs-coupled GPCRs; Kd ~1 nM each) → cAMP ↑ → PKA → NF-κB suppression + CREB activation. In research models, VIP drives: (1) immune anti-inflammation: inhibits TNF-α, IL-6, IL-12, IFN-γ, IL-17, COX-2/PGE2, iNOS/NO; stimulates IL-10, IL-1Ra; promotes Treg; inhibits Th1/Th17; (2) vascular/airway smooth muscle relaxation (bronchodilation, vasodilation); (3) circadian rhythm synchronization via SCN VPAC2; (4) GI motility, secretion, and epithelial immune homeostasis. Aviptadil (synthetic VIP; Zyesami) received FDA Fast Track/Breakthrough designation for COVID-19 ARDS (not broadly approved). Short plasma half-life (<1 min); C-terminal amidation required for full receptor affinity. Research Use Only (RUO). Updated April 2026.
VPAC1 and VPAC2 both bind VIP with ~1 nM affinity and couple primarily through Gs to cAMP, but differ importantly in expression and regulation. VPAC1 is constitutively expressed on lymphocytes (T cells, thymocytes), macrophages, monocytes, and dendritic cells in resting conditions, as well as in liver, lung, and intestinal epithelium. It is the primary receptor for VIP’s homeostatic neuroimmune regulation. VPAC2 is expressed on mast cells (where it is the only VIP receptor), vascular and airway smooth muscle, specific brain regions (thalamus, suprachiasmatic nucleus/SCN, hippocampus), pancreas, kidney, and heart. In immune cells, VPAC2 expression is dynamically upregulated by LPS and inflammatory stimuli — VPAC1 may be constitutively expressed but VPAC2 appears during active immune responses. The suprachiasmatic nucleus VPAC2 is critical for circadian rhythm synchronization; this is not a VPAC1 function. For research requiring receptor subtype attribution: selective VPAC1 agonists ([K15,R16,L27]VIP1–7-GRF8–27) and VPAC2 agonists (Ro 25-1553) are published pharmacological tools for receptor-specific dissection.
VIP’s plasma half-life is less than one minute due to rapid degradation by endopeptidases and carboxypeptidases present in plasma and serum. In cell culture experiments with serum-containing media (10% FBS), VIP is degraded within minutes of addition, meaning that VIP added to serum-containing medium for a 4–24 hour experiment is unlikely to be active for more than the first 15–30 minutes. For sustained VIP receptor activation studies, researchers have several options: (1) use low-serum (0.5–2%) or serum-free conditions and add fresh VIP at intervals; (2) add protease inhibitors to culture medium; (3) use metabolically stabilized VIP analogs (several published analogs are available for sustained receptor activation); or (4) specifically study acute VIP receptor activation (cAMP measurement 5–15 minutes post-addition), where the short half-life is less critical. For in vivo mouse studies, local injection near the target tissue or intrathecal administration routes are used rather than systemic IV/SC, where rapid degradation would severely limit bioavailability. Research studies claiming sustained VIP effects should document how rapid peptide degradation was controlled.
VIP and PACAP (pituitary adenylyl cyclase-activating polypeptide) are structurally homologous (68% sequence identity), both bind VPAC1 and VPAC2 with similar nanomolar affinity, and both produce similar anti-inflammatory effects through those receptors. The critical pharmacological distinction is the PAC1 receptor: PACAP binds PAC1 with high affinity (Kd ~0.5 nM) while VIP does not (Kd >500 nM — essentially no VIP/PAC1 interaction at research concentrations). PAC1 activates both adenylyl cyclase/cAMP and phospholipase C/IP3/Ca²⁺ signaling and is expressed predominantly in specific CNS regions (olfactory bulb, hypothalamus, hippocampus) and adrenal medulla. In practice: using VIP for a study yields VPAC1 + VPAC2 activation only; using PACAP yields VPAC1 + VPAC2 + PAC1 activation. Researchers studying VIP-specific VPAC1/VPAC2 biology should use VIP; researchers needing to understand the full PACAP receptor system (including PAC1’s CNS-dominant role) should use PACAP38. Comparing VIP vs. PACAP responses in the same system is a well-established research design for determining what component of an observed effect is PAC1-mediated.
Aviptadil (Zyesami; manufactured by NeuroRx/Relief Therapeutics) is a synthetic form of VIP formulated for IV and inhalation administration, which received FDA Fast Track designation and Breakthrough Therapy designation for COVID-19-associated respiratory failure/ARDS. The clinical rationale was VIP’s known anti-inflammatory effects in pulmonary tissue (alveolar macrophage VPAC1-mediated cytokine suppression; type II pneumocyte VIP receptor expression and protection; anti-inflammatory reduction of cytokine storm) and its bronchodilatory and pulmonary vasodilatory effects. Published Phase 2 data showed respiratory improvement in some research subjects subgroups. As of April 2026, Aviptadil is not broadly research-grade for any indication. For researchers, the Aviptadil/Zyesami development context is relevant because it establishes: (1) VIP can be formulated and used safely at research-relevant doses; (2) the pulmonary biology rationale for VIP is supported by regulatory-grade clinical interest; (3) the VPAC1-mediated alveolar anti-inflammatory pathway is a validated target. YPB research-grade VIP is not Aviptadil and is not equivalent to any compound preparation.
Yes. YourPeptideBrand.com provides white-label dropship for VIP in a 10mg configuration (VIP10; Research Use Only). White-label storefronts include pre-built RUO-compliant product pages with VPAC1/VPAC2 mechanism descriptions, neuroimmune anti-inflammatory biology context, short half-life research protocol notes, and COA library links. Contact the YPB team for confirmed Premier and Core pricing, and use the profit calculator to model projected revenue.
Every VIP batch includes a lot-specific COA: HPLC purity (≥98%), MS confirmation at ~3,326 Da (C-terminal amidated form; free acid form would show ~3,327 Da; the 1 Da difference from C-terminal amidation is measurable by high-resolution MS and confirms the biologically active form), endotoxin (<1 EU/mg), TAMC, and TYMC. The C-terminal amidation confirmation (~3,326 Da) is the critical quality parameter, as VIP without C-terminal amidation shows significantly reduced VPAC1/VPAC2 binding affinity. For critical receptor binding studies, a functional bioassay (cAMP induction in VPAC1-expressing cells at expected EC50) provides the gold-standard biological activity confirmation. All lots are traceable through the batch-specific COA library.
Position VIP as the pleiotropic neuroimmune neuropeptide — the endogenous signaling molecule at the intersection of the nervous system and immune system with a uniquely broad research application profile: anti-inflammatory immune modulation (macrophages, T cells, DCs via VPAC1); pulmonary biology (bronchodilation, alveolar protection, Aviptadil clinical context); circadian rhythm (SCN VPAC2); GI/enteric immune homeostasis; and vascular biology (smooth muscle relaxation). Key catalog positioning narrative: “VIP sits at the neuroimmune interface — the peptide that tells the immune system to stand down.” Its clinical connection through Aviptadil (FDA Fast Track designation) provides regulatory credibility for the anti-inflammatory pulmonary research angle without constituting approval claims. 15,000+ PubMed publications establishes VIP as a foundational established research tool rather than an emerging compound, and the 10mg configuration makes it accessible for high-use research labs.
Key Takeaways
Research Takeaways
- 28-AA secretin/glucagon superfamily; 68% homology with PACAP: VIP = VPAC1 + VPAC2 only; PACAP = VPAC1 + VPAC2 + PAC1. VIP does not bind PAC1 (Kd >500 nM).
- VPAC1/VPAC2 Gs/cAMP/PKA anti-inflammatory cascade: NF-κB suppression; TNF-α/IL-6/IL-12/IL-17/IFN-γ inhibition; IL-10/IL-1Ra stimulation; Treg promotion; iNOS/COX-2 inhibition. VPAC1 constitutive on T cells/macrophages; VPAC2 on mast cells/smooth muscle/SCN.
- Short plasma half-life (<1 min): Rapid peptidase degradation; serum-free or protease inhibitor conditions required for sustained activation studies; C-terminal amidation required for full receptor affinity.
- C-terminal amidation COA check: ~3,326 Da (amidated) vs. ~3,327 Da (free acid). 1 Da difference by high-res MS; amidation required for full VPAC1/VPAC2 binding.
- Broad research applications: Neuroimmune anti-inflammation, pulmonary biology, circadian (SCN VPAC2), IBD, vascular smooth muscle, gut-brain axis.
- Aviptadil/Zyesami clinical context: FDA Fast Track + Breakthrough designation for COVID-19 ARDS; validates pulmonary VIP biology; not broadly approved.
Business Takeaways
- 15,000+ PubMed publications — one of the most-studied neuropeptides; broad established research audience across neuroimmunology, pulmonary, and GI fields.
- Only VPAC1/VPAC2 agonist in YPB catalog — unique mechanism covering neuroimmune, vascular, circadian, and pulmonary biology from a single compound.
- VIP + KPV + LL-37 + ARA-290 anti-inflammatory quartet covers VPAC neuroimmune, MC1R epithelial, innate AMP, and IRR injury-selective mechanisms from a single inflammation research buyer audience.
- Contact YPB for confirmed pricing on VIP10 (10mg configuration).
Ready to add VIP to your research catalog? Book a consultation with the YPB team.
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