EdnrB

EDNRB, or endothelin receptor type B, is a G protein-coupled receptor encoded by the EDNRB gene in humans. It binds endothelin peptides ET-1, ET-2, and ET-3, with ET-3 showing particularly high affinity. The receptor is expressed on vascular endothelium and neural crest–derived cells, including those that form the enteric nervous system and melanocytes. In endothelial cells, EDNRB activation promotes release of nitric oxide and prostacyclin, contributing to vasodilation, while in neural crest–derived cells it regulates migration, proliferation, and differentiation during development.

Signaling through EDNRB is primarily via the Gq/11 pathway, activating phospholipase C, generating IP3 and DAG, and increasing intracellular calcium. The receptor can also participate in alternative signaling routes in certain contexts. Developmentally, EDNRB signaling is crucial for the proper colonization of the gut by neural crest cells; disruption can result in Hirschsprung disease, a condition characterized by aganglionic segments of the colon and intestinal obstruction. EDNRB also influences pigmentation by regulating melanocyte development; mutations can contribute to pigmentary abnormalities and, in combination with other genes such as SOX10 or EDN3, to Waardenburg syndrome type 4.

Genetic variants in EDNRB have been associated with Hirschsprung disease and related neurocristopathies, reflecting its role in neural crest cell biology. The condition exhibits genetic heterogeneity and may involve interactions with EDN3, SOX10, and other pathway components. Pharmacologically, endothelin receptor antagonists that block EDNRB (often alongside EDNRA inhibition) are used to treat pulmonary arterial hypertension, highlighting the receptor’s relevance as a drug target.