Endothelin receptor type A (ET_A) and Endothelin receptor type B (ET_B) (ET_A and ET_B)

Endothelin receptor type A (ET_A) and endothelin receptor type B (ET_B) are class A G protein-coupled receptors (GPCRs) that serve as the primary molecular targets for the 21-amino-acid peptide endothelins (ET-1, ET-2, ET-3)[1][2][3]. ET_A is predominantly responsible for mediating vasoconstriction and cell proliferation, while ET_B can mediate both vasodilation (through release of nitric oxide in endothelial cells) and vasoconstriction (when present on smooth muscle cells)[2][4]. Both receptors are widely expressed in the cardiovascular, renal, immune, and central nervous systems, as well as in various cancers. Therapeutic antagonists targeting these receptors, especially ET_A-selective blockers, are approved for the treatment of pulmonary arterial hypertension and are under investigation for cancer and fibrosis. The receptors share a 7-transmembrane domain architecture, characteristic of GPCRs, and signal primarily through G_q/11 (Ca^2+ signaling), G_s, and G_i proteins to regulate multiple downstream pathways[1][4][6]. Safety concerns with pharmacological inhibition include hepatotoxicity, fluid retention, and reproductive toxicity.

Other names

ET_A receptorET_B receptorEndothelin-1 receptor (for ET_A)Endothelin receptor type AEndothelin receptor type BEndothelin receptors (collective term)

ET_A antagonists: Block ET_A-mediated vasoconstriction and proliferation by inhibiting endothelin-1 binding ET_B antagonists: Block ET_B-mediated responses, with variable vascular effects Agonists: Activate GPCR-coupled signal transduction, elevating intracellular Ca^2+ and activating downstream effectors such as protein kinase C (PKC) and phospholipase Cβ (PLCβ) Antibodies: Bind to the extracellular region of ET_A, blocking ligand-induced activation and downstream signaling