新規ヒト電位駆動性有機酸トランスポーターＮＰＴ４（ＳＬＣ１７Ａ３）による薬物輸送

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  • S9-4. Drug Transport Mediated by a Novel Human Voltage-Driven Organic Anion Transporter NPT4 (<I>SLC17A3</I>)

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In kidney, the secretion of organic anions (OAs) takes place in the renal proximal tubular cells via at least two steps. The first is the transport of OAs from the blood across the basolateral membrane into the proximal tubules. The transport of p-aminohippurate (PAH), a prototypical substrate for the renal organic anion transport systems, across the basolateral membrane of proximal tubular cells against the electrochemical gradient occurs in exchange for intracellular dicarboxylates. Two organic anion transporters, OAT1 (SLC22A6) and OAT3 (SLC22A8), have been proposed to be responsible for this step. The second step is the exit of OAs across the apical membrane at the tubular epithelial cells into the urine. Voltage-driven organic anion transport plays an important role for this step. However, the molecular nature and precise functional properties of these efflux systems were largely unknown. Recently, the characteristics of human type I sodium-phosphate transporter hNPT4 (SLC17A3), an orphan transporter, has been analyzed using Xenopus oocyte expression system. hNPT4 acts as a voltage-driven transporter for several OAs such as PAH, estrone sulfate, diuretic drugs and urate. This finding will complete a model of the secretion of OAs in the renal tubular cell, where OAs in the blood are taken up via OAT1 and/or OAT3 and intracellular OAs exit from the cell into the tubular lumen via hNPT4.

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  • 臨床薬理

    臨床薬理 42 (3), 149-150, 2011

    一般社団法人 日本臨床薬理学会

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