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.
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