Foscarnet, an inhibitor of the sodium-phosphate cotransporter NaPi-IIa, inhibits phosphorylation of glycogen synthase kinase-3 beta by lithium in the rat kidney cortex

作者：Uwai Yuichi^*; Kawasaki Tatsuya; Nabekura Tomohiro

来源：Drug Metabolism and Pharmacokinetics, 2016, 31(3): 256-259.

DOI：10.1016/j.dmpk.2016.02.003

• Lithium
• GSK3 beta
• Phosphorylation
• Kidney cortex
• Foscarnet
• Reabsorption

Lithium, which is used in the treatment of and prophylaxis for bipolar disease, inhibits glycogen synthase kinase-3 beta (GSK3 beta) by producing its phosphorylated form (p-GSK3 beta). GSK3 beta plays a role in apoptosis and some kinds of acute kidney injuries, and the formation of p-GSK3 beta is considered to contribute to protection against acute kidney injury. We previously reported that the sodium-phosphate cotransporter NaPi-IIa (SLC34A1) mediated the reabsorption of lithium in the rat kidney. In the present study, the phosphorylation status of GSK3 beta in the kidney cortex of rats administered lithium chloride and foscarnet, a typical inhibitor of NaPi-IIa, was examined using Western blotting. Under a 2-h infusion of lithium chloride, the plasma concentration of lithium was 1.06 mEq/l, and its renal clearance was calculated as 1.18 ml/min/kg, which was 29.6% of creatinine clearance. The abundance of p-GSK3 beta in the kidney cortex was augmented by the administration of lithium. The simultaneous infusion of foscarnet increased the renal clearance of lithium and its ratio to creatinine clearance as well as the urinary excretion of phosphate. Foscarnet also inhibited the lithium-induced phosphorylation of GSK3 beta. These results suggest that the reabsorption of lithium by NaPi-IIa triggers the phosphorylation of GSK3 beta in the rat kidney cortex.

• 出版日期2016-6