Lithium Interferes with the Urinary Excretion of Phenolsulfonphthalein in Rats: Involvement of a Reduced Content of α-Ketoglutarate, the Driving Force for Organic Anion Transporters OAT1 and OAT3, in the Kidney Cortex

Pharmacology. 2015;96(5-6):278-83. doi: 10.1159/000441253. Epub 2015 Oct 30.

Abstract

Aims: Lithium is effective in the treatment for bipolar disorder and is known to influence renal functions. The purpose of this study was to examine the effects of lithium on the renal organic anion transport system.

Methods: Pharmacokinetic experiments using rats and Western blotting were conducted.

Results: Until 60 min after the intravenous injection of phenolsulfonphthalein, a typical substrate of the renal organic anion transporters, as a bolus, 41.2% of the dose was recovered in the urine, and the infusion of lithium chloride dose-dependently interfered with its renal excretion. No significant changes were observed in the expression levels of rat organic anion transporters rOAT1 and rOAT3, and the content of α-ketoglutarate, the driving force for both transporters, was significantly decreased in the kidney cortex of rats administered lithium.

Conclusion: These findings represented the dysfunction of the renal organic anion transport system in rats by lithium. As the mechanism, the reduced driving force for rOAT1 and rOAT3 was suggested to be involved at least in part.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antimanic Agents / adverse effects*
  • Blotting, Western
  • Dose-Response Relationship, Drug
  • Ketoglutaric Acids / metabolism*
  • Kidney Cortex / drug effects*
  • Kidney Cortex / metabolism
  • Kidney Function Tests
  • Lithium Chloride / adverse effects*
  • Male
  • Organic Anion Transport Protein 1 / metabolism*
  • Organic Anion Transporters, Sodium-Independent / metabolism*
  • Phenolsulfonphthalein / pharmacokinetics*
  • Rats, Wistar
  • Substrate Specificity
  • Tissue Distribution
  • Urine / chemistry

Substances

  • Antimanic Agents
  • Ketoglutaric Acids
  • Organic Anion Transport Protein 1
  • Organic Anion Transporters, Sodium-Independent
  • Slc22a6 protein, rat
  • organic anion transport protein 3
  • Lithium Chloride
  • Phenolsulfonphthalein