Physiological and pharmacokinetic roles of H+/organic cation antiporters (MATE/SLC47A).
Vectorial secretion of cationic compounds across tubular epithelial cells is an important function of the kidney. This uni-directed transport is mediated by two cooperative functions, which are membrane potential-dependent organic cation transporters at the basolateral membranes and H+/organic cation antiporters at the brush-border membranes. More than 10 years ago, the basolateral organic cation transporters (OCT1-3/SLC22A1-3) were isolated, and molecular understandings for the basolateral entry of cationic drugs have been greatly advanced. However, the molecular nature of H+/organic cation antiport systems remains unclear. Recently, mammalian orthologues of the multidrug and toxin extrusion (MATE) family of bacteria have been isolated and clarified to function as H+/organic cation antiporters. In this commentary, the molecular characteristics and pharmacokinetic roles of mammalian MATEs are critically overviewed focusing on the renal secretion of cationic drugs.
Terada
Tomohiro
T
Department of Pharmacy, Kyoto University Hospital, Faculty of Medicine, Kyoto University, Sakyo-ku, Kyoto 606-8507, Japan.
Inui
Ken-ichi
K
D000595:Amino Acid Sequence; D000818:Animals; D017920:Antiporters / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D006801:Humans; D006859:Hydrogen / Q000502:physiology; D007668:Kidney / Q000378:metabolism; D008969:Molecular Sequence Data; D009928:Organ Specificity; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004364:Pharmaceutical Preparations / Q000378:metabolism* / Q000652:urine; D013379:Substrate Specificity; D015262:Xenobiotics / Q000493:pharmacokinetics* / Q000652:urine
D017920:Antiporters; D027701:Organic Cation Transport Proteins; D004364:Pharmaceutical Preparations; D015262:Xenobiotics; D006859:Hydrogen