title: Sodium-phosphate cotransporter mediates reabsorption of lithium in rat kidney.
abstract: Lithium, used for the treatment of bipolar disorders, is reabsorbed via sodium-transport system in the proximal tubule. This step causes intra-/inter-individual difference of lithium disposition, and it has not been unclear which transporter contributes. In this study, we examined effect of foscarnet and parathyroid hormone (PTH), inactivators for sodium-phosphate cotransporter, and phlorizin, a typical inhibitor for sodium-glucose cotransporter, on the disposition of lithium in rats. Their intravenous administration stimulated urinary excretion of phosphate or glucose. After the intravenous injection of lithium chloride as a bolus, plasma concentration of lithium decreased time-dependently. The renal clearance of lithium was calculated to be 0.740 ml/min/kg in control rats, and this was 26.7% of creatinine clearance. Foscarnet and PTH significantly increased the renal clearance of lithium and its ratio to creatinine clearance, suggesting that they prevented the reabsorption of lithium. No effect of phlorizin on the renal handling of lithium was recognized. In control rats, the renal clearance of lithium showed a strong correlation with the renal excretion rate of phosphate, compared with creatinine clearance. These findings suggest that sodium-phosphate cotransporter reabsorbs lithium in the rat kidney. Furthermore, its contribution was estimated to be more than 65.9% in the lithium reabsorption. And, this study raised the possibility that therapeutic outcome of lithium is related with the functional expression of sodium-phosphate cotransporter in the kidney.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University, Nagoya, Japan. Electronic address: yuuwai@dpc.agu.ac.jp.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Uwai
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Arima
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Takatsu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Furuta
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kawasaki
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University, Nagoya, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Nabekura
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D017245:Foscarnet / Q000494:pharmacology; D006029:Glycosuria; D007668:Kidney / Q000378:metabolism*; D018021:Lithium Chloride / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology; D010695:Phlorhizin / Q000494:pharmacology; D010710:Phosphates / Q000097:blood / Q000652:urine; D017208:Rats, Wistar; D050608:Sodium-Phosphate Cotransporter Proteins / Q000378:metabolism*
chemical_list: D001786:Blood Glucose; D010281:Parathyroid Hormone; D010710:Phosphates; D050608:Sodium-Phosphate Cotransporter Proteins; D017245:Foscarnet; D010695:Phlorhizin; D018021:Lithium Chloride
keywords: Foscarnet; Kidney; Lithium; Parathyroid hormone; Reabsorption; Sodium-phosphate cotransporter