VIP (vasoactive intestinal peptide) is a 28-amino acid neuropeptide originally isolated from porcine intestine and subsequently found throughout the peripheral and central nervous system, immune system, and respiratory tract. It acts on two GPCRs — VPAC1 and VPAC2 — both Gs-coupled, driving cAMP-mediated signalling in smooth muscle (vasodilation, bronchodilation), immune cells (anti-inflammatory), enteric neurons (motility), and hypothalamic suprachiasmatic nucleus neurons (circadian rhythm). VIP is one of the most broadly expressed regulatory neuropeptides in the body and serves as the reference VPAC1/2 agonist for neuroimmune, pulmonary, gastrointestinal, and circadian research.
Bronchodilation: VPAC2 on airway smooth muscle → cAMP → bronchodilation. Relevant to pulmonary hypertension and asthma models
Circadian pacemaker: VPAC2 on SCN neurons → phase-resetting of circadian oscillation. VIP neurons in SCN are essential for circadian rhythm synchronisation
Enteric nervous system: VIP is the primary inhibitory neuropeptide of GI motility — VPAC1/2 on smooth muscle → relaxation of lower oesophageal sphincter and colonic smooth muscle
VIP and pulmonary arterial hypertension — clinical context
VIP is deficient in lung tissue of pulmonary arterial hypertension (PAH) patients vs controls. VIP inhalation reduces mean pulmonary artery pressure and pulmonary vascular resistance in PAH. This positions VIP as the reference vasodilatory neuropeptide for pulmonary hypertension models — mechanistically distinct from sildenafil (PDE5) and bosentan (endothelin receptor antagonist).
Key Research Studies & Data
Study
Model
Finding
Hamidi et al. 2006 (Am J Respir)
PAH patients — VIP inhalation
Reduced mean pulmonary artery pressure and pulmonary vascular resistance
Delgado et al. 2001 (J Immunol)
Murine arthritis model
VIP reduced joint inflammation, TNF-a/IL-6, macrophage infiltration via VPAC1
Aton et al. 2005 (Nat Neurosci)
VPAC2 knockout mice
Loss of circadian rhythmicity in SCN — established VPAC2 as essential for circadian pacemaker
Research Protocols — VIP
Protocol 1: Pulmonary hypertension model (MCT rat)
Monocrotaline 60 mg/kg SC day 0 → VIP 50-200 pmol/kg/min IV from day 14 × 2 weeks. Right ventricular systolic pressure (RVSP), Fulton index (RV/LV+S), pulmonary vascular morphometry, eNOS/iNOS expression, plasma cAMP.
VIP 1 µM applied to SCN slices at CT6 or CT12. PER2::LUC bioluminescence recording. Phase shift magnitude and direction — maps VIP timing-dependence of circadian gating.
Protocol 4: GI motility (colonic manometry)
VIP 10-100 pmol intracolonic in anaesthetised rat. Colonic pressure recording, smooth muscle tension (ex vivo organ bath VIP 0.1-100 nM), cAMP in colonic smooth muscle, VPAC2 IHC.
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Frequently Asked Questions
What is VIP (vasoactive intestinal peptide)?
VIP is a 28 amino acid neuropeptide expressed throughout the nervous system, GI tract, and lungs. It activates VPAC1 and VPAC2 (Gs-coupled) to drive vasodilation, bronchodilation, immune suppression, and circadian rhythm pacing in the SCN.
What is the VPAC1/VPAC2 difference?
Both are Gs-coupled class B GPCRs. VPAC1 is the high-affinity VIP receptor on immune cells, vascular endothelium, and GI epithelium. VPAC2 is dominant in airway smooth muscle, SCN neurons, and pancreas. VPAC2 knockout mice have specific circadian and bronchomotor phenotypes.
How does VIP reduce inflammation?
VPAC1 on macrophages and T-cells → cAMP → PKA → reduced TNF-a, IL-6, IL-12; increased IL-10 and IL-4. VIP also shifts T-helper balance toward Th2 and T-regulatory phenotypes.
What is the connection between VIP and pulmonary arterial hypertension?
VIP is deficient in PAH lung tissue. VIP inhalation reduces pulmonary vascular resistance by activating VPAC1/2 on pulmonary arterial smooth muscle → cAMP → vasodilation. Mechanistically distinct from PDE5 inhibitors and endothelin receptor antagonists.
What formats does QSC supply VIP in?
QSC supplies VIP as lyophilised research vials, ≥99% purity HPLC verified with Janoshik COA. Ships from domestic warehouses in USA, EU, UK, Canada, and Australia.
