Endothelin Receptor A Antibodies

The endothelin type A receptor (ETₐ), encoded by EDNRA, is a class A G protein-coupled receptor with higher affinity for endothelin-1 and endothelin-2 than for endothelin-3. It signals predominantly through Gq/11, activating phospholipase C and increasing intracellular calcium, and can also engage G12/13–RhoA signaling. ETₐ is expressed predominantly in vascular smooth muscle and is also found in cardiomyocytes, fibroblasts, and several other cell types. In vascular smooth muscle, endothelin-1 activation of ETₐ produces potent, sustained vasoconstriction. Persistent ETₐ signaling can promote cell proliferation, fibrosis, and vascular remodeling. Agonist exposure can induce receptor phosphorylation, β-arrestin recruitment, and internalization, after which ETₐ can recycle to the plasma membrane. The selective ETₐ antagonist ambrisentan is used clinically to treat pulmonary arterial hypertension. Atrasentan, another selective ETₐ antagonist, is approved in the United States to reduce proteinuria in adults with primary IgA nephropathy at risk of rapid disease progression.