Department of Pharmacology, Toxicology and Therapeutics, The University of Kansas Medical Center, Kansas City, KS 66160, USA.
Br J Pharmacol. 2012 Mar;165(5):1260-87. doi: 10.1111/j.1476-5381.2011.01724.x.
The human organic anion and cation transporters are classified within two SLC superfamilies. Superfamily SLCO (formerly SLC21A) consists of organic anion transporting polypeptides (OATPs), while the organic anion transporters (OATs) and the organic cation transporters (OCTs) are classified in the SLC22A superfamily. Individual members of each superfamily are expressed in essentially every epithelium throughout the body, where they play a significant role in drug absorption, distribution and elimination. Substrates of OATPs are mainly large hydrophobic organic anions, while OATs transport smaller and more hydrophilic organic anions and OCTs transport organic cations. In addition to endogenous substrates, such as steroids, hormones and neurotransmitters, numerous drugs and other xenobiotics are transported by these proteins, including statins, antivirals, antibiotics and anticancer drugs. Expression of OATPs, OATs and OCTs can be regulated at the protein or transcriptional level and appears to vary within each family by both protein and tissue type. All three superfamilies consist of 12 transmembrane domain proteins that have intracellular termini. Although no crystal structures have yet been determined, combinations of homology modelling and mutation experiments have been used to explore the mechanism of substrate recognition and transport. Several polymorphisms identified in members of these superfamilies have been shown to affect pharmacokinetics of their drug substrates, confirming the importance of these drug transporters for efficient pharmacological therapy. This review, unlike other reviews that focus on a single transporter family, briefly summarizes the current knowledge of all the functionally characterized human organic anion and cation drug uptake transporters of the SLCO and the SLC22A superfamilies.
人类有机阴离子和阳离子转运体被分类为两个 SLC 超家族。SLC21A 超家族（以前称为 SLC21A）包含有机阴离子转运多肽 (OATP)，而有机阴离子转运体 (OAT) 和有机阳离子转运体 (OCT) 则被分类在 SLC22A 超家族中。每个超家族的个体成员基本上在体内的每个上皮细胞中表达，在那里它们在药物吸收、分布和消除中发挥重要作用。OATP 的底物主要是大的疏水性有机阴离子，而 OAT 则转运较小的亲水性有机阴离子，OCT 则转运有机阳离子。除了内源性底物，如甾体、激素和神经递质外，许多药物和其他外源性物质也由这些蛋白质转运，包括他汀类药物、抗病毒药物、抗生素和抗癌药物。OATPs、OATs 和 OCTs 的表达可以在蛋白质或转录水平上进行调节，并且似乎在每个家族中都因蛋白质和组织类型的不同而有所差异。这三个超家族都由 12 个跨膜域蛋白组成，这些蛋白具有细胞内末端。尽管尚未确定晶体结构，但同源建模和突变实验的组合已被用于探索底物识别和转运的机制。已经发现这些超家族成员中的一些多态性会影响其药物底物的药代动力学，这证实了这些药物转运体对于有效药物治疗的重要性。与仅关注单一转运体家族的其他综述不同，这篇综述简要总结了当前关于 SLC2CO 和 SLC22A 超家族中所有功能表征的人类有机阴离子和阳离子药物摄取转运体的知识。
