Endothelin receptor type A (ET_A) (ET_A)

Endothelin receptor type A (ET_A) is a G protein-coupled receptor primarily expressed on vascular smooth muscle cells, where it mediates the potent vasoconstrictive and mitogenic effects of endothelin-1 (ET-1) (UniProt P25101). Upon binding ET-1, the receptor activates the Gq/11 signaling pathway, leading to increased intracellular calcium levels and sustained muscle contraction (StatPearls NBK537027). This receptor plays a critical role in maintaining vascular tone and blood pressure, but its overactivation is a key driver in the pathogenesis of pulmonary arterial hypertension (PAH) and chronic kidney disease (PubMed PMID: 25431066). In these conditions, ET_A-mediated signaling promotes excessive vasoconstriction, vascular remodeling, and fibrosis. Consequently, ET_A has become a major therapeutic target, with several selective and dual receptor antagonists, such as ambrisentan and macitentan, approved for clinical use (PubChem CID 9807722). These medications help reduce pulmonary vascular resistance and slow the progression of renal damage, though they require careful monitoring for side effects such as fluid retention, potential liver injury, and significant teratogenic risk.

Other names

EDNRAEndothelin A receptorET-A receptorhET-AREndothelin-1 receptor

Competitive antagonism of the endothelin receptor type A, which inhibits the binding of the potent vasoconstrictor endothelin-1, thereby preventing Gq-mediated phospholipase C activation and subsequent intracellular calcium release.