Effect of diuretics on oxidative phosphorylation of dog kidney mitochondria

G. Eknoyan, H. Sawa, S. Hyde, J. M. Wood, A. Schwartz, Wadi N. Suki

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

An effect of diuretics on cellular metabolism has been shown. In order to examine further the direct effect of diuretics on renal mitochondria, their effect on isolated cortical (C) and outer medullary (OM) mitochondrial respiration was examined. Oxygen consumption rate (QO2) was measured in a Gilson oxygraph utilizing either glutamate malate or succinate as substrate. QO2, expressed in nanoatoms of O2 per milligram of protein per minute, was always higher in C than OM: 140.7 ± 2.8 vs. 121.2 ± 2.4 (P<0.001) with glutamate malate and 181.1±6.3 vs. 129.7±5.2 (P<0.001) with succinate A dose response curve was constructed for each of the following: sodium ethacrynate, furosemide, chlorothiazide, acetazolamide and chlormerodrin. All diuretics inhibited C and OM equally. The 50% inhibitory molar concentration for EA was 6.2 x 10-4; for furosemide 1.5 x 10-3; for chlorothiazide 8.1 x 10-3; for acetazolamide 10.8 x 10-3; and for chlomerodrin 3.1 x 10-5. Neither cysteine nor dithiothreitol inhibited the effect of EA. The effect of chlormerodrin was abolished by cysteine. These results demonstrate that while a difference exists between C and OM mitochondria during control studies, each of the diuretics examined exerted an equal inhibitory effect on mitochondrial respiration from both C and OM. Mercurials are the most potent inhibitors and presumably exert their effect by reacting with sulfhydryl groups. They are followed in potency by ethacrynic acid, furosemide, chlorothiazide and acetazolamide.

Original languageEnglish (US)
Pages (from-to)614-623
Number of pages10
JournalJournal of Pharmacology and Experimental Therapeutics
Volume194
Issue number3
StatePublished - Dec 1 1975

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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