Organic Cation Transporters in Human Physiology, Pharmacology, and Toxicology

被引:54
|
作者
Samodelov, Sophia L. [1 ]
Kullak-Ublick, Gerd A. [1 ,2 ]
Gai, Zhibo [1 ,3 ]
Visentin, Michele [1 ]
机构
[1] Univ Zurich, Univ Hosp Zurich, Dept Clin Pharmacol & Toxicol, CH-8006 Zurich, Switzerland
[2] Novartis Pharmaceut, Global Drug Dev, CMO & Patient Safety, Mechanist Safety, CH-4056 Basel, Switzerland
[3] Shandong Univ Tradit Chinese Med, Expt Ctr, Jinan 250355, Peoples R China
基金
瑞士国家科学基金会;
关键词
hepatotoxicity; nephrotoxicity; organic cation transporter; solute carrier; TRIMETHYLAMINE-N-OXIDE; CISPLATIN-INDUCED NEPHROTOXICITY; TOXIN EXTRUSION 1; L-CARNITINE; DOWN-REGULATION; FUNCTIONAL EXPRESSION; SERUM CREATININE; UP-REGULATION; OCT1; SLC22A1; MOLECULAR-IDENTIFICATION;
D O I
10.3390/ijms21217890
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Individual cells and epithelia control the chemical exchange with the surrounding environment by the fine-tuned expression, localization, and function of an array of transmembrane proteins that dictate the selective permeability of the lipid bilayer to small molecules, as actual gatekeepers to the interface with the extracellular space. Among the variety of channels, transporters, and pumps that localize to cell membrane, organic cation transporters (OCTs) are considered to be extremely relevant in the transport across the plasma membrane of the majority of the endogenous substances and drugs that are positively charged near or at physiological pH. In humans, the following six organic cation transporters have been characterized in regards to their respective substrates, all belonging to the solute carrier 22 (SLC22) family: the organic cation transporters 1, 2, and 3 (OCT1-3); the organic cation/carnitine transporter novel 1 and 2 (OCTN1 and N2); and the organic cation transporter 6 (OCT6). OCTs are highly expressed on the plasma membrane of polarized epithelia, thus, playing a key role in intestinal absorption and renal reabsorption of nutrients (e.g., choline and carnitine), in the elimination of waste products (e.g., trimethylamine and trimethylamine N-oxide), and in the kinetic profile and therapeutic index of several drugs (e.g., metformin and platinum derivatives). As part of the Special Issue Physiology, Biochemistry, and Pharmacology of Transporters for Organic Cations, this article critically presents the physio-pathological, pharmacological, and toxicological roles of OCTs in the tissues in which they are primarily expressed.
引用
收藏
页码:1 / 21
页数:21
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