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

Endothelin receptors ETA and ETB are G protein-coupled receptors that mediate the physiological and pathophysiological actions of endothelins, particularly endothelin-1 (ET-1), the most potent endogenous vasoconstrictor known (UniProt P25101, P24530). ETA receptors are predominantly expressed on vascular smooth muscle cells, where their activation triggers potent, sustained vasoconstriction and promotes cellular hypertrophy and proliferation (StatPearls, Endothelin Receptor Antagonists). In contrast, ETB receptors are located on both endothelial cells—where they stimulate the release of vasodilators like nitric oxide and prostacyclin and assist in ET-1 clearance—and on smooth muscle cells, where they can contribute to vasoconstriction (PubMed PMID: 30135018). Overexpression or overactivity of these receptors is critically involved in the pathogenesis of pulmonary arterial hypertension (PAH), systemic hypertension, and various forms of renal and cardiac fibrosis (PubMed PMID: 36803125). Therapeutic strategies focus on endothelin receptor antagonists (ERAs), which include dual antagonists (blocking both ETA and ETB) and selective ETA antagonists, to reduce vascular resistance and inhibit remodeling (NIH, PubChem). While effective, these therapies require careful monitoring due to risks of liver injury, significant fluid retention, and severe teratogenic potential (FDA Label, Tracleer).

Other names

EDNRAEDNRBET-A receptorET-B receptorEndothelin-1 receptorEndothelin receptor AEndothelin receptor BhET-ARhET-BR

Endothelin receptor antagonism (competitive inhibition of endothelin-1 binding to ETA and/or ETB receptors)