Endothelin--a new family of endothelium-derived peptides with widespread biological properties

Endothelin (ET) is a novel family of three isopeptides (ET-1, ET-2, ET-3) each containing twenty-one amino acids and two disulfide bonds. Initially isolated from the supernatant of cultured porcine aortic endothelial cells, ET is stored as a preproform and released through an unusual proteolytic cleavage. In general, ET-1, ET-2, ET-3 differ quantitatively but not qualitatively in their biologic activity. ET have potent contractile activity in a variety of isolated tissues including arteries veins, trachea, duodenum urinary bladder and uterus. In vivo, ET possesses potent vasodilator and vasoconstrictor properties. Although the mechanisms mediating the hemodynamic effects of ET are not entirely clarified, recent evidence indicates a role for endothelium-derived relaxant factor (EDRF), protein kinase C and extracellular calcium. Moreover, ET appears to produce inflammation and bronchoconstriction through the formation of arachidonic acid metabolites via the cyclooxygenase pathway. The presence of ET binding sites in blood vessels and in several organ systems suggests ET may have important regulatory functions, which remain to be determined.