title: Endothelin-1 regulates H⁺-ATPase-dependent transepithelial H⁺ secretion in zebrafish.
abstract: 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 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.
authors.affiliation: Graduate Institute of Life Sciences (Y.-J.G., P.-P.H.), National Defense Medical Center, Taipei, Taiwan; Institute of Cellular and Organismic Biology (Y.-J.G., C.-Y.Y., P.-P.H.), Academia Sinica, Taipei, Taiwan; Department of Life Science (Y.-C.T.), National Taiwan Normal University and Institute of Fisheries Science (C.-Y.Y.), National Taiwan University, Taipei, Taiwan.
authors.forename: Ying-Jey
authors.initials: YJ
authors.lastname: Guh
authors.forename: Yung-Che
authors.initials: YC
authors.lastname: Tseng
authors.forename: Chao-Yew
authors.initials: CY
authors.lastname: Yang
authors.forename: Pung-Pung
authors.initials: PP
authors.lastname: Hwang
mesh_terms: D000136:Acid-Base Equilibrium / Q000187:drug effects; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D018942:Macrolides / Q000494:pharmacology; D008297:Male; D049990:Membrane Transport Modulators / Q000494:pharmacology; D060172:Morpholinos / Q000494:pharmacology; D021122:Protein Subunits / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D044022:Receptor, Endothelin A / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012867:Skin / Q000187:drug effects / Q000196:embryology / Q000378:metabolism*; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000378:metabolism; D025262:Vacuolar Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
chemical_list: D065130:Endothelin A Receptor Antagonists; D019332:Endothelin-1; D004791:Enzyme Inhibitors; D018942:Macrolides; D049990:Membrane Transport Modulators; D060172:Morpholinos; D021122:Protein Subunits; D044022:Receptor, Endothelin A; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D029961:Zebrafish Proteins; C414282:edn1 protein, zebrafish; C040929:bafilomycin A1; C520788:V-ATPase subunit A, zebrafish; D025262:Vacuolar Proton-Translocating ATPases