Endothelin 1

Endothelin 1 is a potent vasoconstrictor peptide produced by vascular endothelial cells. It is one of the three isoforms of endothelin (ET), the others being ET-2 and ET-3. Endothelin 1 is a 21-amino acid peptide with a molecular weight of approximately 2.5 kDa. It is involved in various physiological and pathological processes, including vasoconstriction, vasodilation, cell proliferation, and inflammation.

Structure and Function

Endothelin 1 is synthesized as a large precursor molecule, preproendothelin, which is cleaved by endopeptidases to produce big endothelin-1. This is further cleaved by endothelin converting enzyme (ECE) to produce the active 21-amino acid peptide. The peptide has two intramolecular disulfide bridges, which contribute to its conformation and biological activity.

Endothelin 1 exerts its effects by binding to two G-protein coupled receptors, ET_A and ET_B. ET_A receptors are predominantly expressed on smooth muscle cells, and their activation leads to vasoconstriction and cell proliferation. ET_B receptors are found on endothelial cells and mediate vasodilation through the release of nitric oxide and prostacyclin.

Role in Disease

Abnormal regulation of endothelin 1 has been implicated in a number of diseases, including hypertension, atherosclerosis, pulmonary arterial hypertension, and heart failure. In these conditions, elevated levels of endothelin 1 contribute to increased vascular tone and remodeling, leading to disease progression. Several drugs that target the endothelin system, such as bosentan and ambrisentan, have been developed for the treatment of pulmonary arterial hypertension.

See Also

• Endothelin receptor
• Endothelin converting enzyme
• Vasoconstriction
• Vasodilation