Endothelin-1 regulates hh ⁺-atpase-dependent transepithelial hh ⁺ secretion in zebrafish

Endothelin-1 (EDN1) is an important regulator of H ⁺ secretion in the mammalian kidney. EDN1 enhances renal tubule H ⁺-ATPase activity, but the underlying mechanism remains unclear. To further elucidate the role of EDN1 in vertebrates' acid-base regulation, the present study used zebrafish as the model to examine the effects of EDN1 and its receptors on transepithelial H ⁺ secretion. Expression of EDN1 and one of its receptors, EDNRAa, was stimulated in zebrafish acclimated to acidic water. A noninvasive scanning ion-selective electrode technique was used toshowthat edn1 overexpression enhancesH ⁺secretion in embryonic skin at 3 days post fertilization.EDNRAa loss of function significantly decreased EDN1- and acid-induced H ⁺ secretion. Abrogationof EDN1-enhanced H ⁺ secretion by a vacuolar H ⁺-ATPase inhibitor (bafilomycin A1) suggests thatEDN1 exerts its action by regulating the H ⁺-ATPase- mediated H ⁺ secretion. EDN1 does not appearto affect H ⁺ secretion through either altering the abundance of H ⁺-ATPase or affecting the celldifferentiation of H ⁺-ATPase-rich ionocytes, because the reduction in secretion upon ednraaknockdown was not accompanied by decreased expression of H ⁺-ATPase or reduced H ⁺- ATPaserichcell density. These findings provide evidence that EDN1 signaling is involved in acid-baseregulation in zebrafish and enhance our understanding of EDN1 regulation of transepithelial H ⁺secretion in vertebrates.