Chemical Identity

Property	Value
Chemical Formula	C109H159N25O32S5
Molecular Weight	2492 Da
CAS Number	117399-94-7
Peptide Class	Vasoactive Peptide (21 amino acids)
Sequence	CSCSSLMDKECVYFCHLDIIW
Disulfide Bonds	2 (Cys1-Cys15, Cys3-Cys11)

Structure

Endothelin 1 (ET-1) is a 21-amino acid vasoconstrictor peptide produced by endothelial cells. It has two intramolecular disulfide bonds forming a compact structure. ET-1 is produced from a 212-amino acid precursor (preproendothelin-1) through furin cleavage to big ET-1 and subsequent cleavage by endothelin-converting enzyme (ECE-1).

Mechanism of Action

ET-1 binds ETA receptors (vasoconstriction, proliferation) and ETB receptors (vasoconstriction on smooth muscle, vasodilation via nitric oxide on endothelium). ETA activation causes potent, long-lasting vasoconstriction through Gq/PLC/IP3/calcium signaling. ET-1 also promotes fibrosis, inflammation, and cell proliferation.

Clinical Applications

• Pulmonary arterial hypertension: ET receptor antagonists (bosentan, ambrisentan)
• Systemic hypertension: Endogenous ET-1 contributes to vascular tone
• Heart failure: Elevated ET-1 levels correlate with severity
• Kidney disease: ET-1 contributes to renal vasoconstriction
• Cancer: ET-1 promotes tumor progression

Pharmacology

• Half-life: 1-2 minutes (plasma), effects last hours (receptor binding)
• Potency: Most potent endogenous vasoconstrictor
• Local action: Primarily paracrine/autocrine
• Clearance: Lungs (first-pass extraction), kidneys

References

• Yanagisawa, M., et al. (1988). Endothelin: a novel potent vasoconstrictor peptide. Nature, 332, 411-415.
• Galié, N., et al. (2004). Bosentan for pulmonary arterial hypertension. New England Journal of Medicine, 351, 1764-1767.