Vasoactive Intestinal Peptide

Chemical Identity

Property	Value
Name	Vasoactive Intestinal Peptide
Gene	VIP (chromosome 6q25.3)
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
Abbreviation	HSDAVFTDNYTRLRKQMAVKKYLNSILN
Length	28 amino acids
Homology	68% identical to secretin, 27% to glucagon
MW	3325.6 Da
PDB Structures	2RB2 (NMR)

Receptors

Receptor	Gene	Distribution	Affinity
VPAC1 (VIPR1)	VIPR1	Lung, GI tract, brain, pancreas	VIP ≈ PACAP
VPAC2 (VIPR2)	VIPR2	Brain, heart, lung, pancreas	VIP ≈ PACAP

Signaling

VIP → VPAC1/VPAC2 → Gαs → Adenylyl cyclase → cAMP
                                    → Vasodilation
                                    → Secretion
                                    → Immunomodulation

Physiological Functions

Cardiovascular

• Potent vasodilation: 1000× more potent than acetylcholine
• Coronary vasodilation: Increases myocardial blood flow
• Pulmonary vasodilation: Primary pulmonary vasodilator
• Hemodynamic effects: ↓ Blood pressure, ↑ cardiac output

GI Function

• Pancreatic secretion: Stimulates bicarbonate and enzyme secretion
• Intestinal secretion: Stimulates water and electrolyte secretion
• Gallbladder relaxation: Relaxes gallbladder smooth muscle
• Gastric acid: Inhibits gastric acid secretion

Immunomodulation

• T-cell activation: Enhances T-cell proliferation
• Cytokine regulation: Modulates cytokine production
• Anti-inflammatory: Reduces NF-κB, TNF-α
• Mast cell modulation: Regulates histamine release

Neurotransmission

• Co-localized with ACh in parasympathetic neurons
• Widespread brain distribution
• Neuroprotective: Anti-apoptotic effects

Clinical Significance

VIPoma (Verner-Morrison Syndrome)

• Tumor: Pancreatic neuroendocrine tumor secreting excess VIP
• Symptoms: Watery diarrhea, hypokalemia, achlorhydria (WDHA)
• Treatment: Octreotide (somatostatin analog), surgery

Pulmonary Hypertension

• VIP deficiency: Impaired pulmonary vasodilation
• Inhaled VIP: Investigational treatment
• Mechanism: cAMP-mediated pulmonary smooth muscle relaxation

Erectile Dysfunction

• VIP is released during sexual arousal
• Topical VIP: Investigational treatment
• Mechanism: Cavernosal vasodilation

Other Applications

• Cerebral vasospasm: VIP reduces vasospasm after subarachnoid hemorrhage
• Hepatoprotection: VIP protects liver cells
• Anti-inflammatory: VIP reduces inflammation in arthritis, IBD

Manufacturing

• SPPS (Fmoc): Standard solid-phase synthesis
• Purification: RP-HPLC, ion-exchange
• Characterization: Mass spectrometry, NMR
• Half-life: ~1-2 minutes (rapid degradation)

References

1. Said SI, Mutt V. “VIP and related peptides.” Annual Review of Physiology 62:387-424, 2000. doi:10.1146/annurev.ph.62.030199.013014
2. Said SI. “Vasoactive intestinal peptide.” Journal of the International Academy of Pediatrics 2:1-10, 2008.
3. Fahrenkrug J. “VIP and PACAP.” Cellular and Molecular Life Sciences 66:2567-2573, 2009.
4. Gaginella TS, Kachur JF. “VIP and intestinal secretion.” Gastroenterology 100:233-242, 1991.
5. Henning RJ, Said SI. “VIP as a cardiovascular protective peptide.” Experimental Biology and Medicine 234:1347-1357, 2009.