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Endothelin （ET/EDN） receptors are members of the class A GPCR family and exist in two isoforms: type A （ETAR/EDNRA） and type B （ETBR/EDNRB）. These receptors exhibit different affinities for three ligands—ET1, ET2, and ET3. ETAR demonstrates a significantly higher affinity for ET1 and ET2 compared to ET3, while ETBR binds all three ligands nonselectively. The binding affinity rank order for the ET-A receptor is: ET1 > ET2 >> ET3.
ETAR mediates its action by associating with G proteins, which activate a phosphatidylinositol-calcium second messenger system. Both angiotensin II receptor type 1 （AT1R） and endothelin-1 receptor type A （ETAR） are G-protein-coupled receptors （GPCRs） found on the surface of various cell types, including immune cells, vascular smooth muscle cells, endothelial cells, and fibroblasts. These receptors are activated by endothelin 1 （ET1） and angiotensin II （AngII）, respectively.