Roles of organic anion transporters (OATs) and a urate transporter (URAT1) in the pathophysiology of human disease

被引:150
作者
Enomoto A. [1 ]
Endou H. [1 ,2 ]
机构
[1] Department of Pharmacology and Toxicology, Kyorin University, School of Medicine, Mitaka, Tokyo 181-8611
[2] Department of Pathology, Department of Clinical Preventive Medicine, Nagoya University School of Medicine, Nagoya
关键词
Organic anion transporter; Organic cation transporter; Urate (uric acid); Urate transporter;
D O I
10.1007/s10157-005-0368-5
中图分类号
学科分类号
摘要
Renal proximal and distal tubules are highly polarized epithelial cells that carry out the specialized directional transport of various solutes. This renal function, which is essential for homeostasis in the body, is achieved through the close pairing of apical and basolateral carriers expressed in the renal epithelial cells. The family of organic anion transporters (OATs), which belong to the major facilitator superfamily (SLC22A), are expressed in the renal epithelial cells to regulate the excretion and reabsorption of endogenous and exogenous organic anions. We now understand that these OATs are crucial components in the renal handling of drugs and their metabolites, and they are implicated in various clinically important drug interactions, and their adverse reactions. In recent years, the molecular entities of these transporters have been identified, and their function and regulatory mechanisms have been partially clarified. Workers in this field have identified URAT1 (urate transporter 1), a novel member of the OAT family that displays unique and selective substrate specificity compared with other multispecific OATs. In the OAT family, URAT1 is the main transporster responsible for human genetic diseases. In this review, we introduce and discuss some novel aspects of OATs, with special emphasis on URAT1, in the context of their biological significance, functional regulation, and roles in human disease. © Japanese Society of Nephrology 2005.
引用
收藏
页码:195 / 205
页数:10
相关论文
共 77 条
  • [1] Sekine T., Cha S.H., Endou H., The multispecific organic anion transporter (OAT) family, Pflügers Arch, 440, pp. 337-50, (2000)
  • [2] Bruckhardt B.C., Bruckhardt G., Transport of organic anions across the basolateral membrane of proximal tubule cells, Rev Physiol Biochem Pharmacol, 146, pp. 95-158, (2003)
  • [3] Sweet D.H., Bush K.T., Nigam S.K., The organic anion transporter family: From physiology to ontogeny and the clinic, Am J Physiol, 281, pp. 197-205, (2001)
  • [4] Koepsell H., Endou H., The SLC22 drug transporter family, Pflügers Arch, 447, pp. 666-76, (2004)
  • [5] Hediger M.A., Romero M.F., Peng J.B., Rolfs A., Takanaga H., Bruford E.A., The ABCs of solute carriers: Physiological, pathological and therapeutic implications of human membrane transport proteins, Pflügers Arch, 447, pp. 465-8, (2004)
  • [6] Sekine T., Watanabe N., Hosoyamada M., Kanai Y., Endou H., Expression cloning and characterization of a novel multispecific organic anion transporter, J Biol Chem, 272, pp. 18526-9, (1997)
  • [7] Sweet D.H., Wolff N.A., Pritchard J.B., Expression cloning and characterization of ROAT1, the basolateral organic anion transporter in rat kidney, J Biol Chem, 272, pp. 30088-95, (1997)
  • [8] Reid G., Wolff N.A., Dautzenberg F.M., Burckhardt G., Cloning of a human renal p-aminohippurate transporter, hROAT1, Kidney Blood Press Res, 21, pp. 233-7, (1998)
  • [9] Hosoyamada M., Sekine T., Kanai Y., Endou H., Molecular cloning and functional expression of a multispecific organic anion transporter from human kidney, Am J Physiol Renal Physiol, 276, pp. 122-8, (1999)
  • [10] Sekine T., Cha S.H., Tsuda M., Apiwattanakul N., Nakajima N., Kanai Y., Indentification of multispecific organic anion transporter 2 expressed predominantly in the liver, FEBS Lett, 429, pp. 179-82, (1998)