摘要
有机阳离子转运系统最初是在进行肾清除研究时被认知的。许多对机体有害的内源性和外源性物质通过肾小球滤过和/或肾小管分泌从肾清除。这些有害物质中的极性有机阳离子需要通过一个转运体介导的过程才能穿过细胞膜,并最终排泄到尿液中。对肾有机阳离子转运体的研究已有数十年。随着对肾有机阳离子转运体的深入研究,人们在其他组织中也发现了它的存在。特别是,肝和肠组织中的有机阳离子转运体被认为是决定药物吸收和分布的因素。在过去的数十年中,人们利用在体模型,离体器官灌注,或从体外组织和细胞水平对有机阳离子转运的机制进行了广泛的研究。特别是,对其分子克隆和特性的研究,使人们对这一重要的溶质转运蛋白超家族的认识得以深入。本文将对有机阳离子转运体的分子克隆和特性、转运机制、组织分布和定位、与有机阳离子的相互作用、调节机制、基因动物模型进行综述,并对人类有机阳离子转运体基因的遗传变异和临床应用前景进行总结。
The organic cation transport systems were initially recognized in studies of renal elimination.A variety of endogenous and exogenous compounds that are harmful to the body are eliminated from the kidney via glomerular filtration and/or active tubular secretion.Among those compounds are polar organic cations that require a transporter-mediated process to cross cellular membrane and be eventually excreted into the urine.The organic cation transport systems in the kidney have been recognized for several decades.Following the insight gained from the kidney,organic cation transporters（OCTs） have also been characterized in other tissues.In particular,the OCTs in the liver and in the intestine have been proposed as important determinants of drug absorption and disposition.Over the past several decades,the mechanisms of organic cation transport have been extensively characterized using in vivo models,ex vivo organ perfusions,in vitro tissue preparations and cell lines.In particular,the molecular cloning and characterization of OCTs have remarkably increased our knowledge of this important subfamily of solute carriers.In this article,we first review the molecular cloning and characterization of OCTs.We will then describe their transport mechanisms,tissue distribution and localization,and their specificity of interaction with organic cations.Regulatory mechanisms and genetic animal models will be reviewed as they provide the most important insight on this class of transporters in recent years.Finally,we will summarize genetic variation in human OCT genes and raise clinical perspectives on these important transporters.
出处
《中南大学学报（医学版）》
CAS
CSCD
北大核心
2011年第10期913-926,共14页
Journal of Central South University ：Medical Science
