Department of Pharmaceutics, Virginia Commonwealth University, Medical College of Virginia Campus, 410 N 12th Street, PO Box 980533, Richmond, VA 23298, USA.
AAPS J. 2013 Jan;15(1):53-69. doi: 10.1208/s12248-012-9413-y. Epub 2012 Oct 9.
Organic solute flux across the basolateral and apical membranes of renal proximal tubule cells is a key process for maintaining systemic homeostasis. It represents an important route for the elimination of metabolic waste products and xenobiotics, as well as for the reclamation of essential compounds. Members of the organic anion transporter (OAT, SLC22) family expressed in proximal tubules comprise one pathway mediating the active renal secretion and reabsorption of organic anions. Many drugs, pesticides, hormones, heavy metal conjugates, components of phytomedicines, and toxins are OAT substrates. Thus, through transporter activity, the kidney can be a target organ for their beneficial or detrimental effects. Detailed knowledge of the OATs expressed in the kidney, their membrane targeting, substrate specificity, and mechanisms of action is essential to understanding organ function and dysfunction. The intracellular processes controlling OAT expression and function, and that can thus modulate kidney transport capacity, are also critical to this understanding. Such knowledge is also providing insight to new areas such as renal transplant research. This review will provide an overview of the OATs for which transport activity has been demonstrated and expression/function in the kidney observed. Examples establishing a role for renal OATs in drug clearance, food/drug-drug interactions, and renal injury and pathology are presented. An update of the current information regarding the regulation of OAT expression is also provided.
有机溶质跨肾近端小管细胞基底外侧和顶膜的通量是维持全身内稳态的关键过程。它是消除代谢废物和外源性化学物质以及回收必需化合物的重要途径。在近端小管中表达的有机阴离子转运体（OAT，SLC22）家族成员构成了介导有机阴离子主动肾分泌和重吸收的途径之一。许多药物、农药、激素、重金属缀合物、植物药成分和毒素都是 OAT 的底物。因此，通过转运体活性，肾脏可能成为它们有益或有害作用的靶器官。详细了解肾脏中表达的 OAT、它们的膜靶向、底物特异性和作用机制对于理解器官功能和功能障碍至关重要。控制 OAT 表达和功能的细胞内过程，从而可以调节肾脏的转运能力，对于这种理解也至关重要。这种知识也为新的领域提供了启示，例如肾移植研究。本文综述了已证实具有转运活性并在肾脏中观察到表达/功能的 OAT。介绍了一些例子，这些例子确定了肾脏 OAT 在药物清除、食物/药物-药物相互作用以及肾脏损伤和病理中的作用。还提供了 OAT 表达调控的最新信息。
