Terada Tomohiro, Inui Ken-ichi
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Biochem Pharmacol. 2008 May 1;75(9):1689-96. doi: 10.1016/j.bcp.2007.12.008. Epub 2007 Dec 27.
Vectorial secretion of cationic compounds across tubular epithelial cells is an important function of the kidney. This uni-directed transport is mediated by two cooperative functions, which are membrane potential-dependent organic cation transporters at the basolateral membranes and H+/organic cation antiporters at the brush-border membranes. More than 10 years ago, the basolateral organic cation transporters (OCT1-3/SLC22A1-3) were isolated, and molecular understandings for the basolateral entry of cationic drugs have been greatly advanced. However, the molecular nature of H+/organic cation antiport systems remains unclear. Recently, mammalian orthologues of the multidrug and toxin extrusion (MATE) family of bacteria have been isolated and clarified to function as H+/organic cation antiporters. In this commentary, the molecular characteristics and pharmacokinetic roles of mammalian MATEs are critically overviewed focusing on the renal secretion of cationic drugs.
阳离子化合物跨肾小管上皮细胞的向量分泌是肾脏的一项重要功能。这种单向转运由两种协同功能介导，即基底外侧膜上依赖膜电位的有机阳离子转运体和刷状缘膜上的H⁺/有机阳离子反向转运体。十多年前，基底外侧有机阳离子转运体（OCT1 - 3/SLC22A1 - 3）被分离出来，对阳离子药物基底外侧进入的分子认识有了很大进展。然而，H⁺/有机阳离子反向转运系统的分子本质仍不清楚。最近，已分离出细菌多药和毒素外排（MATE）家族的哺乳动物直系同源物，并阐明其作为H⁺/有机阳离子反向转运体发挥作用。在这篇评论中，重点围绕阳离子药物的肾脏分泌，对哺乳动物MATEs的分子特征和药代动力学作用进行了批判性综述。
