Shen Hong, Lai Yurong, Rodrigues A David
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Research and Development, Princeton, New Jersey (H.S., Y.L.), and Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer World Wide Research and Development, Groton, Connecticut (A.D.R.)
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Research and Development, Princeton, New Jersey (H.S., Y.L.), and Department of Pharmacokinetics, Dynamics, and Metabolism, Pfizer World Wide Research and Development, Groton, Connecticut (A.D.R.).
Drug Metab Dispos. 2017 Feb;45(2):228-236. doi: 10.1124/dmd.116.072264. Epub 2016 Nov 21.
As a member of the solute carrier 22A (SLC22A) family, organic anion transporter 2 (OAT2; SLC22A7) is emerging as an important drug transporter because of its expression in both the liver and kidney, two major eliminating organs, and its ability to transport not only a wide variety of xenobiotics but also numerous physiologically important endogenous compounds, like creatinine and cGMP. However, OAT2 has received relatively little attention compared with other OATs and solute carriers (SLCs), like organic cation transporters, sodium-dependent taurocholate cotransporting polypeptide, multidrug and toxin extrusion proteins, and organic anion-transporting polypeptides. Overall, the literature describing OAT2 is rapidly evolving, with numerous publications contradicting each other regarding the transport mechanism, tissue distribution, and transport of creatinine and cGMP, two important endogenous OAT2 substrates. Despite its status as a liver and kidney SLC, tools for assessing its activity and inhibition are lacking, and its role in drug disposition and elimination remains to be defined. The current review focuses on the available and emerging literature describing OAT2. We envision that OAT2 will gain more prominence as its expression, substrate, and inhibitor profile is investigated further and compared with other SLCs.
作为溶质载体22A（SLC22A）家族的一员，有机阴离子转运体2（OAT2；SLC22A7）正逐渐成为一种重要的药物转运体，因为它在肝脏和肾脏这两个主要的排泄器官中均有表达，并且不仅能够转运多种外源性物质，还能转运许多具有重要生理意义的内源性化合物，如肌酐和环磷酸鸟苷。然而，与其他有机阴离子转运体和溶质载体（SLC）相比，如有机阳离子转运体、钠依赖性牛磺胆酸盐共转运多肽、多药和毒素外排蛋白以及有机阴离子转运多肽，OAT2受到的关注相对较少。总体而言，描述OAT2的文献正在迅速发展，众多出版物在转运机制、组织分布以及肌酐和环磷酸鸟苷（OAT2的两种重要内源性底物）的转运方面相互矛盾。尽管OAT2是肝脏和肾脏中的一种SLC，但缺乏评估其活性和抑制作用的工具，其在药物处置和消除中的作用仍有待确定。本综述重点关注描述OAT2的现有文献和新出现的文献。我们预计，随着对OAT2的表达、底物和抑制剂谱的进一步研究，并与其他SLC进行比较，OAT2将受到更多关注。
