ABSTRACT
In 1988, a graduate student in Japan published a stunning paper in the journal Nature about the isolation
and characterization of a new, 21-residue peptide produced by porcine aortic endothelial cells as the most potent vasoconstrictor, called endothelin.1 The vasoconstrictor activity of endothelin was at least 10 times more potent than that reported for angiotensin II, and 100 times more potent, on a molar basis, than norepinephrine. Since then, over 16,000 publications listing endothelin as a key word have appeared in the scientific literature. This peptide, now termed endothelin 1 (ET1; Figure 34.1), was subsequently found to be part of a family of endothelins, which includes ET2, ET3 and the sarafotoxins (isolated from the venom of the Israeli burrowing asp).2 The active form of ET1 is derived from a 39-amino acid precursor peptide, “big ET1,” following proteolytic cleavage of the C-terminal portion of the molecule by an endothelin-converting enzyme.3
