EDNRA

EDNRA, or endothelin receptor type A, is a human gene that encodes the endothelin receptor type A (ET_A), a G protein-coupled receptor. Its primary ligands are endothelin-1, endothelin-2, and endothelin-3, with endothelin-1 showing the highest affinity for ET_A. The receptor is expressed in vascular smooth muscle cells and certain neurons, where it mediates endothelin-1–induced vasoconstriction and contributes to vascular remodeling and proliferation.

ET_A is a seven-transmembrane-domain GPCR that signals mainly through Gq/11 proteins. Upon ligand binding, phospholipase C beta is activated, producing IP3 and DAG, which raise intracellular calcium and activate protein kinase C. This signaling promotes vascular smooth muscle contraction and can stimulate cell proliferation. Receptor activity is regulated by desensitization and internalization via beta-arrestins.

Physiological roles of EDNRA signaling include regulation of vascular tone and blood pressure, with particular importance in the pulmonary vasculature. It also has involvement in development, notably in neural crest–derived tissues and cardiovascular formation, reflecting its conserved role in vascular biology.

Clinical relevance of EDNRA signaling is seen in diseases characterized by excessive vasoconstriction and vascular remodeling, such as pulmonary arterial hypertension and systemic hypertension. Pharmacological blockade of ET_A, and in some cases dual blockade of ET_A and ET_B, is a therapeutic strategy for PAH. Selective ETA antagonists (for example, ambrisentan) and dual antagonists (such as bosentan and macitentan) are used in clinical practice.

EDNRA belongs to the endothelin receptor family within the broader class of G protein-coupled receptors. The gene is conserved across vertebrates, reflecting its fundamental role in cardiovascular biology.