Historical review: Endothelin.

Endothelin (ET) is a potent vasoconstrictive peptide that was isolated initially from the conditioned medium of cultured endothelial cells. In 1988, details of the isolation and identification, amino acid sequence, cDNA sequence and pharmacology of ET were published. Subsequently, ET isoforms, ET receptors and endothelin-converting enzyme (ECE) were cloned. Because ET was thought to be important in cardiovascular homeostasis, many investigators focused on the physiological and pathophysiological significance of ET. Accordingly, ET receptor antagonists and ECE inhibitors have been developed rapidly, mostly for the treatment of cardiovascular diseases. The field of molecular biology has provided valuable information about ET, including evidence that the ET system plays important roles in the early development of the neural crest and, thus, in the formation of organs. These results now present new avenues of ET research.