Molecular and Structural Biology of Endothelin Receptors

The discovery of the vasodilatory factors prostacyclin and nitric oxide that are secreted by, and act on, the endothelium and underlying vascular smooth muscle, led to the search for counter-regulatory vasoconstrictory substances.1–4 In 1988, Yanagisawa and colleagues reported the discovery of an endothelium-derived, 21 amino acid peptide with potent and long-lasting vasoconstrictive and pressor actions.5 This peptide was termed endothelin-1 (ET-1) and is one of a family of three related mammalian peptides. The three peptides are closely related to the sarafotoxin peptides found in the venom of the Israeli burrowing asp, Actractaspic engaddensis and it has become part of the lore surrounding ET-1 that the extremely potent vasoconstrictory effects of the sarafotoxins led to the demise of Cleopatra.