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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acid-Base Equilibrium / drug effects
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Animals
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Biological Transport, Active / drug effects
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Endothelin A Receptor Antagonists
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Endothelin-1 / biosynthesis
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Endothelin-1 / genetics
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Endothelin-1 / metabolism*
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Enzyme Inhibitors / pharmacology
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Female
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Gene Expression Regulation, Developmental / drug effects
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Hydrogen-Ion Concentration
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Macrolides / pharmacology
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Male
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Membrane Transport Modulators / pharmacology
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Morpholinos / pharmacology
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Protein Subunits / antagonists & inhibitors
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Protein Subunits / genetics
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Protein Subunits / metabolism
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Receptor, Endothelin A / genetics
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Receptor, Endothelin A / metabolism*
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Signal Transduction* / drug effects
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Skin / drug effects
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Skin / embryology
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Skin / metabolism*
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Sodium-Hydrogen Exchanger 3
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Sodium-Hydrogen Exchangers / antagonists & inhibitors
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Sodium-Hydrogen Exchangers / metabolism
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Vacuolar Proton-Translocating ATPases / antagonists & inhibitors
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Vacuolar Proton-Translocating ATPases / genetics
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Vacuolar Proton-Translocating ATPases / metabolism*
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Zebrafish / embryology
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Zebrafish / metabolism*
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Zebrafish Proteins / antagonists & inhibitors
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Zebrafish Proteins / biosynthesis
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Zebrafish Proteins / genetics
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Zebrafish Proteins / metabolism*
Substances
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Endothelin A Receptor Antagonists
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Endothelin-1
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Enzyme Inhibitors
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Macrolides
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Membrane Transport Modulators
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Morpholinos
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Protein Subunits
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Receptor, Endothelin A
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Sodium-Hydrogen Exchanger 3
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Sodium-Hydrogen Exchangers
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Zebrafish Proteins
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edn1 protein, zebrafish
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bafilomycin A1
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V-ATPase subunit A, zebrafish
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Vacuolar Proton-Translocating ATPases