Department of Pharmaceutics, School of Pharmacy, Aichi Gakuin University, Nagoya, Japan.
Physiol Res. 2021 Aug 31;70(4):655-659. doi: 10.33549/physiolres.934568. Epub 2021 Jun 1.
Lithium is used in the treatment of bipolar disorder. We previously demonstrated that two types of transporters mediate the tubular reabsorption of lithium in rats, and suggested that sodium-dependent phosphate transporters play a role in lithium reabsorption with high affinity. In the present study, we examined sex differences in lithium reabsorption in rats. When lithium chloride was infused at 60 µg/min, creatinine clearance and the renal clearance of lithium were lower, and the plasma concentration of lithium was higher in female rats. These values reflected the higher fractional reabsorption of lithium in female rats. In rats infused with lithium chloride at 6 µg/min, the pharmacokinetic parameters of lithium examined were all similar in both sexes. The fractional reabsorption of lithium was decreased by foscarnet, a representative inhibitor of sodium-dependent phosphate transporters, in male and female rats when lithium chloride was infused at the low rate. Among the candidate transporters mediating lithium reabsorption examined herein, the mRNA expression of only PiT2, a sodium-dependent phosphate transporter, exhibited sexual dimorphism. The present results demonstrated sex differences in the tubular reabsorption of lithium with low affinity in rats.
锂被用于治疗双相情感障碍。我们之前的研究表明，两种转运体介导了大鼠肾小管对锂的重吸收，并且提示钠依赖的磷酸转运体对高亲和力的锂重吸收发挥作用。在本研究中，我们检测了大鼠中锂重吸收的性别差异。当以 60μg/min 的速度输注氯化锂时，肌酐清除率和锂的肾清除率降低，并且雌性大鼠的血浆锂浓度更高。这些值反映了雌性大鼠中更高的锂重吸收率。在以 6μg/min 的速度输注氯化锂的大鼠中，当以低速率输注时，两性大鼠的锂的药代动力学参数均相似。当以低速率输注氯化锂时，膦甲酸，一种钠依赖的磷酸转运体的代表性抑制剂，降低了两性大鼠的锂的重吸收率。在本研究中检测的介导锂重吸收的候选转运体中，只有 PiT2（一种钠依赖的磷酸转运体）的 mRNA 表达存在性别二态性。本研究结果表明，大鼠中存在低亲和力的肾小管锂重吸收的性别差异。
