Organic cation transporters.
Over the last 15 years, a number of transporters that translocate organic cations were characterized functionally and also identified on the molecular level. Organic cations include endogenous compounds such as monoamine neurotransmitters, choline, and coenzymes, but also numerous drugs and xenobiotics. Some of the cloned organic cation transporters accept one main substrate or structurally similar compounds (oligospecific transporters), while others translocate a variety of structurally diverse organic cations (polyspecific transporters). This review provides a survey of cloned organic cation transporters and tentative models that illustrate how different types of organic cation transporters, expressed at specific subcellular sites in hepatocytes and renal proximal tubular cells, are assembled into an integrated functional framework. We briefly describe oligospecific Na(+)- and Cl(-)-dependent monoamine neurotransmitter transporters ( SLC6-family), high-affinity choline transporters ( SLC5-family), and high-affinity thiamine transporters ( SLC19-family), as well as polyspecific transporters that translocate some organic cations next to their preferred, noncationic substrates. The polyspecific cation transporters of the SLC22 family including the subtypes OCT1-3 and OCTN1-2 are presented in detail, covering the current knowledge about distribution, substrate specificity, and recent data on their electrical properties and regulation. Moreover, we discuss artificial and spontaneous mutations of transporters of the SLC22 family that provide novel insight as to the function of specific protein domains. Finally, we discuss the clinical potential of the increasing knowledge about polymorphisms and mutations in polyspecific organic cation transporters.
Koepsell
H
H
Institut für Anatomie und Zellbiologie, Bayerischen Julius-Maximilians-Universität, Koellikerstr. 6, 97070 Würzburg, Germany. Hermann@Koepsell.de
Schmitt
B M
BM
Gorboulev
V
V
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D027682:Cation Transport Proteins / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D002412:Cations; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008954:Models, Biological; D008969:Molecular Sequence Data; D016296:Mutagenesis; D009154:Mutation; D010802:Phylogeny; D011110:Polymorphism, Genetic; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D027682:Cation Transport Proteins; D002412:Cations; D008024:Ligands; D012333:RNA, Messenger