Endothelins (ET-1, 2 and 3) are 21-residue peptides with two disulfide bridges and a highly conserved carboxy terminal. ET-1, the most significant isoform, is a potent vasoconstrictor and mitogen that exerts its biological effects through binding to its two G protein-coupled receptors: ET(A) and ET(B). ET(A) receptors are expressed on vascular smooth muscle cells and mediate vasoconstrictive and proliferative responses to ET-1. ET(B) receptors are mainly located on endothelial cells where they clear ET-1 from circulation and mediate vasodilation via the release of nitric oxide. ET-1 has been associated with a variety of serious diseases such as pulmonary hypertension, heart failure, prostate cancer and renal dysfunction.
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