Abstract

The effects of uricosuric agents have been evaluated in vitro with indices of uric acid uptake into human urate transporter 1 (URAT1)-overexpressed oocytes or cells. In the present study, we evaluated a method using primary human renal proximal tubule epithelial cells (RPTECs). Pretreatment of RPTECs with insulin significantly increased the uptake of uric acid into these cells. The uric acid uptake was inhibited in a concentration-dependent manner by the URAT1 inhibitors benzbromarone and dotinurad. Therefore, effects of uricosuric agents can be evaluated by the novel method, which is closer to the physiological system compared with previous methods.

摘要

已在体外评估了尿酸排泄剂的作用，其指标为人尿酸转运蛋白 1 (URAT1) 过表达的卵母细胞或细胞中的尿酸摄取指数。在本研究中，我们评估了一种使用原代人肾近端小管上皮细胞 (RPTECs) 的方法。用胰岛素预处理 RPTECs 显着增加了这些细胞对尿酸的吸收。URAT1抑制剂苯溴马隆和dotinurad以浓度依赖性方式抑制尿酸摄取。因此，与以往的方法相比，该方法更接近生理系统，可以评估尿酸排泄剂的效果。