Storage Stability
Endothelin-3 (ET-3) is a 21-amino-acid vasoactive peptide from the endothelin family, generated from big-endothelin-3 by endothelin-converting enzyme-1. Unlike ET-1, ET-3 shows preferential selectivity for the ETB receptor and plays critical roles in melanocyte development, neural crest cell migration, and intestinal innervation.
Mechanism of Action
- ETB receptor activation triggers endothelial nitric oxide synthase (eNOS), causing vasodilation and opposing the vasoconstrictor effects of ET-1 via ETA
- Stimulates melanocyte stem cell proliferation and migration from neural crest during development via ETB on melanoblasts
- Required for enteric nervous system development; ET-3/ETB signaling maintains neural crest progenitor pools in developing gut
- Promotes histamine release from mast cells and mediates bronchoconstriction at high concentrations
- ETB-mediated clearance of circulating endothelins in pulmonary vasculature regulates systemic levels
Research Findings
- Mutations in ET-3 or ETB gene cause Hirschsprung disease and Waardenburg-Shah syndrome (aganglionic megacolon + pigmentation defects)
- ET-3 null mice lack enteric neurons in the colon and show coat color spotting due to absent melanocytes
- ET-3 promotes survival of precursor cells that form sympathetic ganglia, adrenal chromaffin cells, and enteric neurons
- Elevated plasma ET-3 in patients with carcinoid tumors and some forms of pulmonary hypertension
- ETB agonists being explored for melanoma metastasis promotion (negative implication) and for gut motility disorders
Research Protocols
- Research peptide: ET-3 at 1-10 nM in cell culture to assess ETB signaling (NO production, calcium mobilization)
- In vivo vascular pharmacology: 1-100 pmol/kg IV bolus in rodent blood pressure studies
- Developmental biology: ET-3 bath application to embryo gut explants at 10-100 nM to study enteric neuron migration
- Not used clinically as a therapeutic; used as pharmacological tool and biomarker
Interactions
- ETB receptor antagonists (BQ788): block ET-3 vasodilatory and developmental effects
- ET-1: competes for ETB binding; ET-3 can displace ET-1 from ETB at equimolar concentrations
- Bosentan/macitentan (dual ETA/ETB antagonists): block ET-3 signaling; relevant for pulmonary hypertension therapy
Safety Profile
Endogenous peptide. Pharmacological doses cause transient vasodilation followed by potential vasoconstriction. Not used as therapeutic agent. Deficiency causes developmental defects (Hirschsprung); excess may contribute to melanoma aggressiveness.
Legal & Regulatory
Research peptide; not approved as therapeutic
Ready to dose Endothelin-3?
Get the exact syringe draw
You have read the research. Now run the math. Pick your vial size and BAC water volume, get IU draw in seconds.
Open the Calculator →
More in Muscle & Anabolic
View all →