Roles of organic anion transporters (OATs) and a urate transporter (URAT1) in the pathophysiology of human disease.
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.
Enomoto
Atsushi
A
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo, 181-8611, Japan.
Endou
Hitoshi
H
D058186:Acute Kidney Injury / Q000503:physiopathology; D000818:Animals; D002331:Carnitine / Q000172:deficiency; D002352:Carrier Proteins / Q000502:physiology*; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D007676:Kidney Failure, Chronic / Q000503:physiopathology; D007684:Kidney Tubules / Q000502:physiology*; D051379:Mice; D027361:Organic Anion Transporters / Q000378:metabolism / Q000502:physiology*; D027701:Organic Cation Transport Proteins / Q000502:physiology; D015499:Renal Tubular Transport, Inborn Errors / Q000235:genetics; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; D014527:Uric Acid / Q000097:blood / Q000378:metabolism
D002352:Carrier Proteins; D016166:Free Radical Scavengers; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; C467737:SLC22A16 protein, human; C109807:SLC22A4 protein, human; C492020:SLC22A5 protein, human; D000074058:Solute Carrier Family 22 Member 5; D027981:Symporters; D014527:Uric Acid; D002331:Carnitine