Sodium-phosphate cotransporter mediates reabsorption of lithium in rat kidney
Sodium-phosphate cotransporter mediates reabsorption of lithium in rat kidney
复制标题
钠-磷酸盐协同转运蛋白介导大鼠肾脏对锂的重吸收
DOI：
10.1016/j.phrs.2014.06.012
复制
发表时间：
2014
影响因子：
9.3
通讯作者：
T.
中科院分区：
文献类型：
--
作者：
Uwai;Y.;Arima;R.;Takatsu;C.;Furuta;R.;Kawasaki;T.;Nabekura;T.
用于治疗双相情感障碍的锂通过近端小管中的钠转运系统被重吸收。这一步骤导致锂处置的个体内/个体间差异，并且尚不清楚哪种转运蛋白起作用。在这项研究中，我们研究了膦甲酸和甲状旁腺激素（PTH），钠-磷酸盐协同转运蛋白的灭活剂，根皮苷，钠-葡萄糖协同转运蛋白的典型抑制剂，对锂在大鼠体内的处置。它们的静脉给药刺激磷酸盐或葡萄糖的尿排泄。静脉推注氯化锂后，血浆锂浓度呈时间依赖性下降。对照组大鼠的肾脏锂清除率为0.740 ml/min/kg，为肌酐清除率的26.7%。膦甲酸和甲状旁腺激素显着增加锂的肾脏清除率及其与肌酸酐清除率的比率，表明它们阻止了锂的重吸收。根皮苷对肾脏处理锂没有影响。在对照组大鼠中，与肌酐清除率相比，锂的肾脏清除率与磷酸盐的肾脏排泄率表现出很强的相关性。这些发现表明钠-磷酸盐协同转运蛋白在大鼠肾脏重吸收锂。此外，它的贡献估计超过65.9%的锂重吸收。并且，本研究提出了锂的治疗结果与肾脏中钠-磷酸盐协同转运蛋白的功能表达有关的可能性。
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.