Endothelin receptor (ETR) (ETR)

The endothelin signaling pathway is a critical regulator of vascular tone and cellular homeostasis, primarily mediated by the interaction of endothelin-1 (ET-1) with two G protein-coupled receptors: Endothelin receptor type A (ETA) and Endothelin receptor type B (ETB) [StatPearls: Endothelin Receptor Antagonists]. ETA receptors are predominantly located on vascular smooth muscle cells and mediate potent, long-lasting vasoconstriction and mitogenesis, while ETB receptors are found on both endothelial cells (mediating vasodilation via nitric oxide) and smooth muscle cells [PubMed: PMC2702237]. Overactivation of this pathway is strongly associated with the pathogenesis of pulmonary arterial hypertension (PAH), where it drives excessive vasoconstriction and vascular remodeling [NIH: Pulmonary Arterial Hypertension]. Pharmacological targeting of this pathway focuses on endothelin receptor antagonists (ERAs), which can be either selective for ETA or dual antagonists for both ETA and ETB [PubMed: 24070120]. These agents are standard-of-care treatments for PAH and have recently shown efficacy in treating proteinuric chronic kidney disease by reducing glomerular pressure and inflammation [The Lancet: Sparsentan in IgA Nephropathy]. However, their use is limited by significant safety concerns, most notably high teratogenic potential and the risk of fluid retention or hepatotoxicity [FDA: Tracleer Label]. Beyond PAH, the pathway is also implicated in systemic hypertension and certain cancers, where it promotes cell survival and angiogenesis [PubMed: 21660136]. Monitoring of patients on these therapies often involves liver function tests and pregnancy screening due to the known risks associated with receptor blockade [StatPearls: Bosentan].

Other names

Endothelin-1 receptorETA receptorETB receptorEDNRAEDNRBEndothelin receptor type AEndothelin receptor type B

Endothelin receptor antagonism