Department of Pharmaceutics, Rutgers, the State University of New Jersey, Piscataway, NJ, USA.
Department of Pharmaceutics, Rutgers, the State University of New Jersey, Piscataway, NJ, USA.
Pharmacol Ther. 2021 Jan;217:107647. doi: 10.1016/j.pharmthera.2020.107647. Epub 2020 Aug 3.
The members of the organic anion transporter (OAT) family are mainly expressed in kidney, liver, placenta, intestine, and brain. These transporters play important roles in the disposition of clinical drugs, pesticides, signaling molecules, heavy metal conjugates, components of phytomedicines, and toxins, and therefore critical for maintaining systemic homeostasis. Alterations in the expression and function of OATs contribute to the intra- and inter-individual variability of the therapeutic efficacy and the toxicity of many drugs, and to many pathophysiological conditions. Consequently, the activity of these transporters must be highly regulated to carry out their normal functions. This review will present an update on the recent advance in understanding the cellular and molecular mechanisms underlying the regulation of renal OATs, emphasizing on the post-translational modification (PTM), the crosstalk among these PTMs, and the remote sensing and signaling network of OATs. Such knowledge will provide significant insights into the roles of these transporters in health and disease.
有机阴离子转运体（OAT）家族的成员主要表达于肾脏、肝脏、胎盘、肠道和大脑。这些转运体在临床药物、农药、信号分子、重金属缀合物、植物药成分和毒素的处置中发挥重要作用，因此对于维持全身内环境稳定至关重要。OAT 表达和功能的改变导致许多药物的治疗效果和毒性在个体内和个体间存在差异，并导致许多病理生理状况。因此，这些转运体的活性必须受到高度调节以发挥其正常功能。本综述将介绍对肾脏 OAT 调节的细胞和分子机制的最新研究进展，重点介绍翻译后修饰（PTM）、这些 PTM 之间的串扰以及 OAT 的远程感应和信号网络。这些知识将为这些转运体在健康和疾病中的作用提供重要的见解。
