Vasoactive Intestinal Peptide (VIP)

Vasoactive Intestinal Peptide (VIP; 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; CAS 40077-57-4; molecular formula C147H237N43O43S; molecular weight 3326.81) is a 28-residue C-terminally amidated peptide originally isolated from porcine duodenum by Sami Said and Viktor Mutt in 1970 as a vasodilator and bronchodilator activity. VIP belongs to the secretin/glucagon/PACAP peptide family and signals through the VPAC1 and VPAC2 G-protein-coupled receptors expressed widely on epithelial, endothelial, smooth muscle, and immune cells. The pharmacological signature is broad: vasodilation and bronchodilation through cAMP elevation in vascular and bronchial smooth muscle, anti-inflammatory effects through suppression of pro-inflammatory cytokine production (TNF, IL-6, IL-12) and induction of regulatory T cell phenotypes, and neuroprotective and anti-apoptotic effects in central nervous system tissue. VIP has been extensively studied as a research tool for VPAC receptor pharmacology and explored clinically for indications including pulmonary arterial hypertension (Aviptadil, Phase 3, mixed results; emergency use authorization for COVID-19 ARDS in some jurisdictions), sarcoidosis, asthma, and Sjogren's syndrome. In integrative medicine and chronic inflammatory response syndrome (CIRS) protocols, VIP is administered as an intranasal spray after Marcons (multiple antibiotic resistant coagulase negative staphylococci) eradication; the protocol was developed by Ritchie Shoemaker and is supported by case-series evidence rather than randomized trials. The compound is not FDA-approved for any chronic indication; intranasal VIP for CIRS is compounded by specialty pharmacies. Plasma half-life is short (less than 2 minutes); the intranasal route provides direct nasal mucosal exposure with limited systemic absorption.