19(S)-hydroxyeicosatetraenoic acid is a potent stimulator of renal Na+-K+-ATPase

Bruno Escalante, J R Falck, Pendri Yadagiri, Lumin Sun, Michal Laniado-Schwartzman

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70 Scopus citations

Abstract

ω- and ω-1 hydroxylations are the major pathways by which arachidonic acid is metabolized in cortical and outer medullary microsomes of rat and rabbit kidneys. It is a cytochrome P450-dependent oxidation leading to the formation of 20-hydroxy- and 19-hydroxy-eicosatetraenoic acids. In this study, we compared the effects of the synthetically prepared ω- and ω-1 metabolites of arachidonic acid on the activity of the renal Na+-K+-ATPase partially purified from rat renal cortical microsomes. 19(S)-hydroxyeicosatetraenoic acid caused a dose related stimulation of Na+-K+-ATPase activity with an EC50 of 3×10-7M. In contrast, neither 19(R)-hydroxyeicosatetraenoic acid, 20-hydroxyeicosatetraenoic acid nor arachidonic acid at 10-6M had any effect on Na+-K+-ATPase activity. In the same preparation, ouabain at 10-3M and 12(R)-hydroxyeicosatetraenoic acid at 10-6M inhibited the enzyme activity by 75% and 60%, respectively. We conclude that 19(S)-hydroxyeicosatetraenoic acid is a specific stimulator of renal Na+-K+-ATPase. Therefore, the formation of 19(S)-hydroxyeicosatetraenoic acid by renal cortical cytochrome P450 ω-1-hydroxylase may contribute to the regulation of renal function by regulating Na+-K+-ATPase which is essential for transtubular transport processes.

Original languageEnglish (US)
Pages (from-to)1269-1274
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume152
Issue number3
DOIs
StatePublished - May 16 1988

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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