Endothelin-1 receptor type A (ETA)

Endothelin-1 receptor type A (ETA) is a G protein-coupled transmembrane receptor belonging to the rhodopsin-type superfamily. It features seven transmembrane domains and an N-terminal signal sequence. ETA specifically binds to endothelin-1 (ET-1), a potent vasoconstrictor, with higher affinity compared to other endothelin subtypes. Upon ET-1 binding, ETA couples with G proteins, activating the phosphatidylinositol-calcium second messenger system and phospholipase, leading to vasoconstriction in vascular smooth muscle cells, cell proliferation, and vascular remodeling. Dysregulation of ETA is implicated in various diseases, including cardiovascular conditions like hypertension, pulmonary hypertension, atherosclerosis, coronary artery disease, restenosis, and transplant arteriosclerosis, as well as certain cancers and kidney diseases. Due to its crucial role in these pathologies, ETA is an important therapeutic target, with selective and dual ETA/ETB antagonists developed for clinical use. Novel therapeutic approaches are also being explored.

Drugs targeting the ETA receptor act primarily as antagonists, blocking the binding of its ligand, endothelin-1 (ET-1). This antagonism prevents the activation of downstream signaling pathways, such as the phosphatidylinositol-calcium system and phospholipase activation, thereby reducing cellular responses like vasoconstriction and cell proliferation.