東京大学医学部附属病院薬剤部Department of Pharmacy, The University of Tokyo Hospital― 223 ―Uric acid is important because of its antioxidative activity and has a causal relationship with hyperuricemia and gout. Like vitamin C, another water-soluble antioxidant, uric acid mainly exists as an anion form (urate) under physiological conditions, therefore, it cannot passively pass through the plasma membrane. Thus, active transport plays a crucial role in regulating urate handling in humans. Nevertheless, known urate transporters cannot explain the whole picture of regulatory mechanisms, suggesting the presence of unknown transporters with physiological significance. To address this issue, we herein focused on sodium-dependent vitamin C transporters (SVCTs)/SLC23As, because a homology search revealed that SVCT1/SLC23A1 and SVCT2/SLC23A2 are the closest to YgfU (a urate transporter in E. coli). To reveal the urate transport ability of SVCTs, we conducted cell-based analyses using transporter-expressing mammalian cells. The results demonstrated that SVCTs are novel urate transporters with lower affinity for urate compared with known urate importers. Moreover, we generated Svct1 knockout mice and found that serum urate levels were lower than control mice. Since Svct1 physiologically functions as a vitamin C re-absorber in the kidney, it could also be involved in renal urate re-uptake. Furthermore, we established a convenient cell-based urate efflux assay system using SVCT2, focusing on the properties of SVCT2 as a sodium-dependent urate importer. Our findings regarding the dual-substrate specificity of SVCTs deepen the understanding of pharmacokinetic control mechanisms of the water-soluble antioxidants in our body.Abstractはじめに尿酸は，ヒトにおけるプリン体の最終代謝産物であり，ビタミンCと同じように抗酸化作用を示す水溶性抗酸化物質でもある．尿酸は受動的に細胞膜を透過しないことから，その体内動態制御にはAnalysis of pharmacokinetic control mechanisms水溶性抗酸化物質の動態制御メカニズムの解析of water-soluble antioxidants高田 龍平Tappei Takada
元のページ ../index.html#225