Pflügers Archiv

, Volume 414, Issue 5, pp 551–557 | Cite as

Renal tubular transport of glutathione in rat kidney

  • Almut Heuner
  • Johann S. Schwegler
  • Stefan Silbernagl
Transport Processes, Metabolism and Endocrinology; Kidney, Gastrointestinal Tract, and Exocrine Glands

Abstract

Filtered glutathione (γ-glutamyl-cysteinyl-glycine or GSH) is rapidly hydrolyzed by brush-border enzymes facing the tubular lumen and is reabsorbed in the form of the constituent amino acids. The first step of hydrolysis is catalyzed by γ-glutamyltransferase (γ-GT). We investigated localization and capacity of the rat renal glutathione degradation/reabsorption during elevation of the filtered load (intravenous infusion of 12 resp. 18 μmol GSH/min). Fractional excretion went up from about 0.003 to 0.31±0.02 SEM during infusion of the lower and to 0.49±0.03 SEM during infusion of the higher glutathione dose. GSH degradation/reabsorption took place along the entire proximal tubule and was partially saturated by a 150–200-fold elevation of the normal filtered load. Net reabsorption of GSH up to the last accessible superficial loop was significantly lower during infusion of 18 μmol GSH/min (0.3 μmol/min) than during infusion of 12 μmol GSH/min (1.6 μmol/min). In further experiments, infusion of 18 μmol GSH/min was preceded by the i.v. administration of acivicin (0.5 mmol/kg body wt.), an inhibitor of γ-GT. In these experiments, fractional glutathione deliveries to late proximal and early distal tubules did not significantly differ from 1, fractional excretion of GSH at the same time was 1.46±0.11 SEM, revealing net secretion of GSH with the final urine. Tubular secretion of GSH in the acivicin-treated animals occurred either in distal tubules and/or collecting ducts or in the proximal tubules of deep nephrons which are not accessible to micropuncture. The low net reabsorption of GSH up to the late proximal tubule during infusion of 18 μmol GSH/min without prior administration of acivicin indicates tubular secretion of GSH along the proximal convolution of superficial nephrons. Net secretion of glutathione with the final urine in the acivicin-treated animals therefore probably originates from proximal tubules of deep nephrons.

Key words

Rat kidney Glutathione γ-Glutamyltransferase Acivicin 

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Copyright information

© Springer-Verlag 1989

Authors and Affiliations

  • Almut Heuner
    • 1
  • Johann S. Schwegler
    • 1
  • Stefan Silbernagl
    • 1
  1. 1.Physiologisches Institut der Universität WürzburgWürzburgFederal Republic of Germany

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