title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: School of Pharmacy, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Uwai
authors.forename: Misato
authors.initials: M
authors.lastname: Tsuge
authors.forename: Yuta
authors.initials: Y
authors.lastname: Tokai
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kawasaki
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nabekura
mesh_terms: D000818:Animals; D018692:Antimanic Agents / Q000009:adverse effects*; D015153:Blotting, Western; D004305:Dose-Response Relationship, Drug; D007656:Ketoglutaric Acids / Q000378:metabolism*; D007672:Kidney Cortex / Q000187:drug effects* / Q000378:metabolism; D007677:Kidney Function Tests; D018021:Lithium Chloride / Q000009:adverse effects*; D008297:Male; D027362:Organic Anion Transport Protein 1 / Q000378:metabolism*; D029362:Organic Anion Transporters, Sodium-Independent / Q000378:metabolism*; D010637:Phenolsulfonphthalein / Q000493:pharmacokinetics*; D017208:Rats, Wistar; D013379:Substrate Specificity; D014018:Tissue Distribution; D014556:Urine / Q000737:chemistry
chemical_list: D018692:Antimanic Agents; D007656:Ketoglutaric Acids; D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; C421043:Slc22a6 protein, rat; C114338:organic anion transport protein 3; D018021:Lithium Chloride; D010637:Phenolsulfonphthalein