Kölz Charlotte, Schaeffeler Elke, Schwab Matthias, Nies Anne T
Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany.
University of Tuebingen, Tuebingen, Germany.
Handb Exp Pharmacol. 2021;266:81-100. doi: 10.1007/164_2021_450.
Organic cation transporters (OCTs) of the solute carrier family (SLC) 22 are the subject of intensive research because they mediate the transport of many clinically-relevant drugs such as the antidiabetic agent metformin, the opioid tramadol, and the antimigraine agent sumatriptan. OCT1 (SLC22A1) and OCT2 (SLC22A2) are highly expressed in human liver and kidney, respectively, while OCT3 (SLC22A3) shows a broader tissue distribution. As suggested from studies using knockout mice, particularly OCT2 and OCT3 appear to be of relevance for brain physiological function and drug response. The knowledge of genetic factors and epigenetic modifications affecting function and expression of OCTs is important for a better understanding of disease mechanisms and for personalized treatment of patients. This review briefly summarizes the impact of genetic variants and epigenetic regulation of OCTs in general. A comprehensive overview is given on the consequences of OCT2 and OCT3 knockout in mice and the implications of genetic OCT2 and OCT3 variants on central nervous system function in humans.
溶质载体家族（SLC）22的有机阳离子转运体（OCTs）是深入研究的对象，因为它们介导许多临床相关药物的转运，如抗糖尿病药物二甲双胍、阿片类药物曲马多和抗偏头痛药物舒马曲坦。OCT1（SLC22A1）和OCT2（SLC22A2）分别在人类肝脏和肾脏中高表达，而OCT3（SLC22A3）表现出更广泛的组织分布。从使用基因敲除小鼠的研究来看，特别是OCT2和OCT3似乎与脑生理功能和药物反应有关。了解影响OCTs功能和表达的遗传因素和表观遗传修饰，对于更好地理解疾病机制和患者的个性化治疗很重要。本综述简要总结了一般情况下OCTs的遗传变异和表观遗传调控的影响。全面概述了小鼠OCT2和OCT3基因敲除的后果以及人类OCT2和OCT3基因变异对中枢神经系统功能的影响。
