VIP (Vasoactive Intestinal Peptide)

VIP (Vasoactive Intestinal Peptide) is a 28 amino acid neuropeptide (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) belonging to the secretin/glucagon superfamily. VIP is expressed throughout the nervous system and gastrointestinal tract, functioning as a neurotransmitter, neuromodulator, and paracrine signalling molecule with potent vasodilatory, bronchodilatory, immunomodulatory, and circadian rhythm-regulating properties.

VIP activates two class B GPCRs: VPAC1 (VIPR1) and VPAC2 (VIPR2), both Gs-coupled and expressed on immune cells, smooth muscle, epithelial cells, and neurons. A third receptor VPAC1/PAC1 also responds to the related peptide PACAP. VIP's Gs coupling raises cAMP via adenylyl cyclase in target cells, activating PKA with downstream effects on gene transcription, ion channels, and secretory machinery.

Circadian biology research positions VIP centrally in the suprachiasmatic nucleus (SCN) oscillator network. VIP released by SCN neurons synchronises the circadian pacemaker: VPAC2 receptors on SCN neurons receive VIP signals that entrain molecular clock gene oscillations across the SCN network. VPAC2 knockout mice show severely disrupted circadian rhythms, establishing VIP/VPAC2 as essential for SCN network synchrony. VIP research in SCN slice preparations examines phase shifts, firing rate changes, and clock gene expression (PER, CRY, BMAL1) following VIP application.

Immunomodulatory research with VIP has characterised its anti-inflammatory profile: VIP reduces TNF-alpha, IL-6, IL-12, and nitric oxide production in LPS-stimulated macrophages and dendritic cells through cAMP/PKA-mediated NFkB suppression. Published research has examined VIP in models of inflammatory bowel disease, rheumatoid arthritis, and neuroinflammation.

Gastrointestinal research examines VIP as a non-adrenergic non-cholinergic (NANC) neurotransmitter driving smooth muscle relaxation, chloride secretion in intestinal epithelium, and pancreatic enzyme secretion.

MW: 3326.8 g/mol. CAS: 37221-79-7. Contains methionine — prepare fresh solutions, store at -80°C to minimise oxidation. Reconstitute in bacteriostatic water at 1mg/mL. For laboratory and analytical research purposes only.

VIP receptor pharmacology research: VPAC1 and VPAC2 can be distinguished pharmacologically using selective antagonists and agonists. VPAC1-selective agonist: [K15, R16, L27]-VIP(1-7)/GRF(8-27) (also called VIP-hybrid). VPAC2-selective agonist: Ro-25-1553 (cyclic peptide). Pan-VPAC antagonist: VIP(6-28) (N-terminally truncated VIP that binds but does not activate). Running VIP alongside these selective tools in parallel cAMP assays (Gs/cAMP/PKA pathway) in VPAC1-HEK293 and VPAC2-HEK293 cell lines characterises VIP's pharmacological profile across both receptor subtypes and provides IC50 and Emax data.

For SCN circadian biology research: acute hypothalamic slices (400µm, coronal, bilateral SCN preserved) in ACSF at 34°C with 95% O2/5% CO2. Apply VIP (100nM-1µM) at defined circadian time points (CT6, CT12, CT18, CT0) by bath perfusion. Record SCN multi-unit activity (MUA) by extracellular electrode before, during, and after VIP application. Calculate phase shift of subsequent activity rhythms. VIP applied at CT6 (mid-subjective day) typically produces phase delays; applied at CT18 (mid-subjective night) produces phase advances in the SCN firing rhythm. This circadian time-dependent phase resetting characterises VIP's role as an SCN synchronising signal. Compare with PACAP (pituitary adenylate cyclase activating polypeptide) which acts on PAC1 receptors in the SCN through a related but distinct circadian input pathway. MW: 3326.8 g/mol. CAS: 37221-79-7. Contains methionine — prepare fresh, store at -80°C. For laboratory and analytical research purposes only.

VIP immunomodulation research in inflammatory bowel disease models: intestinal organoid cultures derived from human colonoscopic biopsies provide the most physiologically relevant model for VIP intestinal biology. Human colonoid monolayers grown on Transwell inserts express functional VPAC1 and VPAC2 receptors on the basolateral surface. Apply VIP (1-100nM) to the basolateral compartment (mimicking submucosal VIP neuron innervation) during inflammatory challenge (IL-1beta 10ng/mL, TNF-alpha 10ng/mL, apical application). Measure TEER as tight junction integrity readout and apical/basolateral cytokine secretion (IL-6, IL-8, TNF-alpha by ELISA). VIP's proposed anti-inflammatory effect in intestinal epithelium operates through VPAC1/Gs/cAMP/PKA-mediated NFkB suppression — confirm this mechanism using the PKA inhibitor H-89 (10µM, 30 minutes pre-treatment) before VIP application. For comparative VPAC pharmacology, include the VPAC2-selective agonist Ro-25-1553 alongside VIP to determine which receptor subtype drives the intestinal epithelial anti-inflammatory effects. MW: 3326.8 g/mol. CAS: 37221-79-7. Contains methionine — prepare fresh, store at -80°C. Reconstitute in bacteriostatic water immediately before use. For laboratory and analytical research purposes only.