Description
VIP-10 – Technical Biochemical Mechanism Profile
(Vasoactive Intestinal Peptide analogue; VPAC receptor agonist – research use only)
VIP-10 is a synthetic analogue of Vasoactive Intestinal Peptide (VIP) engineered to selectively activate VPAC1 and VPAC2 receptors with increased metabolic stability.
VPAC1/2 are Gs-coupled GPCRs widely expressed on neuronal, endocrine, and immune cells.
Their activation strongly induces adenylyl cyclase → cAMP → PKA signaling, along with downstream Epac, CREB transcription, eNOS/NO production, and immune-regulatory gene suppression through NF-κB inhibition.
✅ 1. Primary Molecular Targets
VPAC1 and VPAC2 Receptors
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Class B GPCRs
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Coupled predominantly to Gsα, with secondary Gq activity in some tissues
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Activation yields:
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↑ cAMP
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PKA phosphorylation of transcription factors
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Ca²⁺ modulation
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NO/eNOS upregulation in endothelial systems
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✅ 2. Core Signaling Pathways
A. cAMP → PKA → CREB (Primary)
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VIP-10 increases intracellular cAMP
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Activates PKA
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PKA phosphorylates CREB
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CREB binds CRE-promoters controlling neuroendocrine and immune genes
Representative CREB-regulated genes:
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BDNF
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NR4A1
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SLC2A4 (GLUT4)
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IL10 (anti-inflammatory)
B. Epac (Exchange Protein Activated by cAMP)
cAMP directly activates Epac1/Epac2, affecting:
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Small GTPase Rap1
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Endothelial barrier stability
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Cytoskeletal reorganization
Measured gene/effector outputs:
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RAP1A
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VASP
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Tight junction proteins (OCLN, CLDN5)
C. NO / eNOS Axis (Endothelial Models)
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PKA and Ca²⁺ signaling upregulate eNOS (NOS3)
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↑ Nitric oxide synthesis
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Vasodilatory and angiogenic gene expression
Relevant targets:
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NOS3
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KDR/VEGFR2
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VEGFA
D. NF-κB Inhibition (Immunomodulatory Context)
VIP-10 suppresses NF-κB activation by:
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Reducing p65 nuclear translocation
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Increasing IκB stabilization
NF-κB-regulated genes decreased in immune models:
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IL1B
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TNFA
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IL6
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COX-2 (PTGS2)
Anti-inflammatory genes increased:
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IL10
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TGF-β
✅ 3. Second Messengers & Enzymatic Outputs
| Second Messenger | Mechanistic Effect |
|---|---|
| cAMP ↑ | Major signaling driver, activating PKA & Epac |
| PKA | CREB phosphorylation, ion channel & eNOS regulation |
| Epac | RAP1 activation, endothelial barrier stabilization |
| Ca²⁺ | Endothelial & neurosecretory signaling |
| NO | Vasodilation & angiogenic responses |
✅ 4. Representative Downstream Gene Targets
| Functional Class | Example Genes |
|---|---|
| Neuroendocrine | BDNF, CREB1, NR4A1 |
| Angiogenesis | VEGFA, KDR, NOS3 |
| Immune regulation | IL10, TGF-β, IL1B, TNFA, IL6, NFKB1 |
| Cytoskeletal / Barrier integrity | VASP, RAP1A, CLDN5, OCLN |
| Metabolic signaling | SLC2A4 (GLUT4), PDK4, PPARGC1A |
✅ 5. Mechanistic Summary
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VIP-10 is a VPAC1/VPAC2 agonist
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Drives cAMP → PKA → CREB transcription
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Activates Epac/Rap1 for cytoskeletal and endothelial effects
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Upregulates eNOS → NO production in vascular models
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Suppresses NF-κB-mediated cytokine transcription
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Alters genes involved in immune modulation, angiogenesis, and cellular metabolism
Research-Only Classification
VIP-10 is supplied exclusively for controlled in-vitro laboratory research.
Not authorized for human or animal administration, therapeutic use, or any biological application outside research environments.