Endothelin

Endothelin

Structure of human endothelin-1

Endothelin is a family of peptides that play a crucial role in the regulation of vascular tone and blood pressure. These peptides are among the most potent vasoconstrictors known and are involved in various physiological and pathological processes.

Structure

Endothelins are small peptides consisting of 21 amino acids. The family includes three isoforms: endothelin-1 (ET-1), endothelin-2 (ET-2), and endothelin-3 (ET-3). Each isoform is encoded by a separate gene and has distinct tissue distribution and function. The structure of endothelins is characterized by two disulfide bridges that form a unique "hairpin" shape, which is essential for their biological activity.

Function

Endothelins primarily function as vasoconstrictors, meaning they cause blood vessels to constrict, leading to an increase in blood pressure. They exert their effects by binding to endothelin receptors, which are G-protein-coupled receptors located on the surface of vascular smooth muscle cells. There are two main types of endothelin receptors: ETA and ETB. The binding of endothelins to these receptors triggers a cascade of intracellular events that result in muscle contraction and vasoconstriction.

Endothelin-1

Endothelin-1 (ET-1) is the most studied and potent member of the endothelin family. It is primarily produced by endothelial cells, the cells lining the interior surface of blood vessels. ET-1 plays a significant role in maintaining vascular homeostasis and is involved in the pathogenesis of various cardiovascular diseases, including hypertension, heart failure, and atherosclerosis.

Endothelin-2 and Endothelin-3

Endothelin-2 (ET-2) and endothelin-3 (ET-3) have similar structures to ET-1 but differ in their tissue distribution and physiological roles. ET-2 is less well understood but is thought to have similar vasoconstrictive properties. ET-3 is primarily found in the gastrointestinal tract and the central nervous system, where it may play a role in neural signaling and gastrointestinal motility.

Pathophysiology

The dysregulation of endothelin production or receptor activity can lead to various pathological conditions. Overproduction of ET-1 is associated with hypertension, pulmonary arterial hypertension, and chronic kidney disease. In these conditions, the excessive vasoconstriction and vascular remodeling contribute to disease progression.

Therapeutic Implications

Given the role of endothelins in disease, they are targets for therapeutic intervention. Endothelin receptor antagonists, such as bosentan and ambrisentan, are used in the treatment of pulmonary arterial hypertension. These drugs block the effects of endothelins, leading to vasodilation and reduced blood pressure.

Related pages

• Vasoconstriction
• Hypertension
• Pulmonary arterial hypertension
• Endothelial cell
• G-protein-coupled receptor