부산대학교 도서관

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 vertebratesʼ 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 to show that edn1 overexpression enhances H secretion in embryonic skin at 3 days post fertilization. EDNRAa loss of function significantly decreased EDN1- and acid-induced H secretion. Abrogation of EDN1-enhanced H secretion by a vacuolar H-ATPase inhibitor (bafilomycin A1) suggests that EDN1 exerts its action by regulating the H-ATPase-mediated H secretion. EDN1 does not appear to affect H secretion through either altering the abundance of H-ATPase or affecting the cell differentiation of H-ATPase-rich ionocytes, because the reduction in secretion upon ednraa knockdown was not accompanied by decreased expression of H-ATPase or reduced H-ATPase-rich cell density. These findings provide evidence that EDN1 signaling is involved in acid-base regulation in zebrafish and enhance our understanding of EDN1 regulation of transepithelial H secretion in vertebrates.