Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
Drug Metab Rev. 2011 Nov;43(4):499-523. doi: 10.3109/03602532.2011.602687. Epub 2011 Sep 17.
Multidrug and toxin extrusion proteins (MATEs; SLC47A) are mammalian transporters being predominately expressed in the brush-border membrane of proximal tubule epithelial cells in the kidney and the canalicular membrane of hepatocytes. Functionally, MATEs act as efflux transporters for organic compounds, thereby mediating the elimination process. Two isoforms, MATE1 and 2, have been identified, and, so far, only a limited number of substrates, including clinically used drugs such as metformin and cimetidine, are known. A knockout mouse model has been established, as well, and is a valuable tool for further systematic pharmacokinetic analyses. In this review, we summarize the progress in MATE research on structural, molecular, functional, and pathophysiological aspects. Consequences of genetic variants for pharmacokinetic alterations and drug therapy are discussed.
多药和毒素外排蛋白（MATEs；SLC47A）是哺乳动物转运蛋白，主要表达在肾脏近端小管上皮细胞的刷状缘膜和肝细胞的胆小管膜。在功能上，MATEs 作为有机化合物的外排转运蛋白，从而介导消除过程。已经鉴定出两种同工型，MATE1 和 2，到目前为止，只知道少数几种底物，包括临床使用的药物，如二甲双胍和西咪替丁。也建立了一种 knockout 小鼠模型，这是进一步进行系统药代动力学分析的有价值的工具。在这篇综述中，我们总结了 MATE 在结构、分子、功能和病理生理方面的研究进展。讨论了遗传变异对药代动力学改变和药物治疗的影响。
