title: Glutathione is a low-affinity substrate of the human sodium-dependent dicarboxylate transporter.
abstract: OBJECTIVE
  During a single pass through the kidneys, more than 80% of glutathione (GSH) is excreted, indicating not only glomerular filtration, but also tubular secretion. The first step in tubular secretion is the uptake of a substance across the basolateral membrane of proximal tubule cells by sodium-dependent and -independent transporters. Due to the dicarboxylate-like structure, we postulated that GSH uptake across the basolateral membrane is mediated by the sodium-dependent dicarboxylate transporter 3 (NaDC3).
  
  
  METHODS
  Tracer uptake and electrophysiologic measurements using a two-electrode voltage clamp device were performed in Xenopus laevis oocytes expressing the human (h)NaDC3.
  
  
  RESULTS
  Uptake of succinate, the reference substrate of hNaDC3, was inhibited by GSH in a dose-dependent manner with an IC50 of 1.88 mM. GSH evoked potential-dependent inward currents, which were abolished under sodium-free conditions. At -60 mV, GSH currents showed saturation kinetics with a KM of 1.65 mM.
  
  
  CONCLUSIONS
  hNaDC3 present at the basolateral membrane of proximal tubule cells mediates sodium-dependent GSH uptake. The kinetic data show that NaDC3 is a low-affinity GSH transporter.
authors.affiliation: Institute of Systemic Physiology and Pathophysiology, University Medical Center Göttingen, Göttingen, Germany.
authors.forename: Lena
authors.initials: L
authors.lastname: Schorbach
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Krick
authors.forename: Gerhard
authors.initials: G
authors.lastname: Burckhardt
authors.forename: Birgitta C
authors.initials: BC
authors.lastname: Burckhardt
mesh_terms: D000818:Animals; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009865:Oocytes / Q000378:metabolism; D029363:Organic Anion Transporters, Sodium-Dependent / Q000235:genetics / Q000378:metabolism*; D018075:RNA, Complementary / Q000235:genetics; D019802:Succinic Acid / Q000378:metabolism*; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis / Q000235:genetics
chemical_list: D029363:Organic Anion Transporters, Sodium-Dependent; D018075:RNA, Complementary; C568530:SLC13A3 protein, human; D027981:Symporters; D019802:Succinic Acid; D005978:Glutathione