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

Endothelin receptor type A (ETA) and endothelin receptor type B (ETB) are closely related class A G protein-coupled receptors (GPCRs) that bind potent endogenous peptides of the endothelin family (ET-1, ET-2, ET-3)[1][2][3][5][6][7]. ETA predominantly mediates vasoconstriction and cellular proliferation, binding ET-1 and ET-2 more strongly, whereas ETB mediates vasodilation via nitric oxide release and facilitates the clearance of ET-1 by binding all isoforms equivalently[6][5][2]. Both receptors have canonical seven-transmembrane domains with distinct ligand affinities and functional roles in vascular homeostasis, blood pressure regulation, and various pathophysiological processes including cardiovascular disease, pulmonary arterial hypertension, renal disease, and some cancers[1][2][5][6][7]. Multiple selective and non-selective endothelin receptor antagonists are approved or in clinical use, particularly for conditions such as pulmonary arterial hypertension[2][6][4][7]. Notable therapeutic challenges include hepatotoxicity, teratogenicity, and fluid retention[2][4]. The receptors are well validated as therapeutic targets and are of ongoing interest for drug development in vascular and proliferative disorders[4][6].

Other names

Endothelin A receptorEndothelin B receptorET_AET_BEDNRAEDNRB

Blockade of ETA causes inhibition of vasoconstriction and vascular cell proliferation Blockade of ETB can interfere with vasodilation and ET-1 clearance but is less commonly targeted therapeutically Mixed antagonists block both receptors to varying degrees Some drugs are selective antagonists (ambrisentan, sitaxentan, zibotentan for ETA; BQ788 for ETB); bosentan and macitentan are non-selective (block both) Mechanistic action primarily involves inhibition of G protein-coupled signal transduction mediated by endothelin peptides