Biology of endothelin receptors in the collecting duct

The collecting duct endothelin (ET) system, involving ET-1 and its two receptors, is involved in the physiologic regulation of renal sodium (Na), water, and acid excretion. Based on in vitro studies and experiments using genetically engineered rodents, the physiology of this system in the collecting duct is being elucidated. Activation of endothelin B (ETB) receptors on principal cells causes inhibition of Na transport through signaling pathways involving src kinase, MAPK1/2, nitric oxide, and possibly prostaglandin E2 (PGE2). Principal-cell ETB receptors also cause inhibition of water transport through protein kinase C-mediated inhibition of AVP-dependent cAMP accumulation. ETB receptors expressed on intercalated cells augment acid secretion, possibly through nitric oxide-dependent mechanisms. The role of endothelin A (ETA) receptors in the collecting duct remains unclear; however, recent evidence suggests that these receptors can exert natriuretic and diuretic effects. Further complexity is lent to this system by studies indicating that ETA and ETB receptors can homo- and hetero-dimerize, with possible functional consequences. This brief review will describe our current state of knowledge about this complex regulatory system in the collecting duct, and will identify clinically relevant issues that need addressing.