Endothelin receptor type A and type B (ETA/ETB)

The endothelin receptor system, comprising the ETA and ETB subtypes, plays a critical role in regulating vascular tone and cardiovascular homeostasis. These G protein-coupled receptors (GPCRs) are primarily activated by endothelin-1 (ET-1), which is among the most potent endogenous vasoconstrictors known. ETA receptors are predominantly located on vascular smooth muscle cells and mediate sustained vasoconstriction, cellular proliferation, and pro-fibrotic signaling. ETB receptors exhibit a more complex dual role: they are found on endothelial cells where they promote vasodilation via the release of nitric oxide and prostacyclin and act as clearance receptors for circulating ET-1, but they can also reside on smooth muscle cells to assist in vasoconstriction. Dysregulation of this system, often involving elevated ET-1 levels, is a key driver in the pathogenesis of pulmonary arterial hypertension (PAH), systemic hypertension, and chronic kidney disease. Therapeutic intervention typically involves endothelin receptor antagonists (ERAs), which may be dual-acting (blocking both subtypes) or ETA-selective, to reduce vascular resistance and prevent remodeling. While highly effective in PAH, these agents carry significant safety considerations, including risks of hepatotoxicity, peripheral edema, and severe teratogenicity.

Other names

EDNRAEDNRBET-AET-BETARETBREndothelin-1 receptorEndothelin A receptorEndothelin B receptor

Antagonism of endothelin receptors to inhibit the binding of endothelin-1, thereby preventing vasoconstriction, vascular remodeling, and fibrosis.