ZFIN ID: ZDB-PUB-140318-8
Endothelin-1 regulates H+-ATPase-dependent transepithelial H+ secretion in zebrafish
Guh, Y.J., Tseng, Y.C., Yang, C.Y., and Hwang, P.P.
Date: 2014
Source: Endocrinology   155(5): 1728-37 (Journal)
Registered Authors: Guh, Ying-Jey, Hwang, Pung Pung, Tseng, Yung-Che
Keywords: none
MeSH Terms:
  • Acid-Base Equilibrium/drug effects
  • Animals
  • Biological Transport, Active/drug effects
  • Endothelin A Receptor Antagonists
  • Endothelin-1/biosynthesis
  • Endothelin-1/genetics
  • Endothelin-1/metabolism*
  • Enzyme Inhibitors/pharmacology
  • Female
  • Gene Expression Regulation, Developmental/drug effects
  • Hydrogen-Ion Concentration
  • Macrolides/pharmacology
  • Male
  • Membrane Transport Modulators/pharmacology
  • Morpholinos/pharmacology
  • Protein Subunits/antagonists & inhibitors
  • Protein Subunits/genetics
  • Protein Subunits/metabolism
  • Receptor, Endothelin A/genetics
  • Receptor, Endothelin A/metabolism*
  • Signal Transduction*/drug effects
  • Skin/drug effects
  • Skin/embryology
  • Skin/metabolism
  • Sodium-Hydrogen Exchangers/antagonists & inhibitors
  • Sodium-Hydrogen Exchangers/metabolism
  • Vacuolar Proton-Translocating ATPases/antagonists & inhibitors
  • Vacuolar Proton-Translocating ATPases/genetics
  • Vacuolar Proton-Translocating ATPases/metabolism*
  • Zebrafish/embryology
  • Zebrafish/metabolism*
  • Zebrafish Proteins/antagonists & inhibitors
  • Zebrafish Proteins/biosynthesis
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 24424055 Full text @ Endocrinology

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 non-invasive 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 (HR) ionocytes, because the reduction in secretion upon ednraa knockdown was not accompanied by decreased expression of H+-ATPase or reduced HR 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.