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

被引:1
作者
Uwai, Yuichi [1 ]
Kawasaki, Tatsuya [1 ]
Nabekura, Tomohiro [1 ]
机构
[1] Aichi Gakuin Univ, Sch Pharm, Dept Pharmaceut, 1-100 Kusumoto Cho, Nagoya, Aichi 464, Japan
关键词
Lithium; GSK3; beta; Phosphorylation; Kidney cortex; Foscarnet; Reabsorption; RENAL PROXIMAL TUBULE; INJURY; APOPTOSIS; CLEARANCE; GSK-3;
D O I
10.1016/j.dmpk.2016.02.003
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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. (C) 2016 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.
引用
收藏
页码:256 / 259
页数:4
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