Organic Anion Transporters and Their Implications in Pharmacotherapy
Open Access
- 28 March 2012
- journal article
- review article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in Pharmacological Reviews
- Vol. 64 (3), 421-449
- https://doi.org/10.1124/pr.111.004614
Abstract
Organic anion transporters play an essential role in the distribution and excretion of numerous endogenous metabolic products and exogenous organic anions, including a host of widely prescribed drugs. The expression and activity of these transporters is influenced by several conditions, including transcriptional regulation, gender-dependent regulation, and genetic variation. In addition, the interaction of these transporters with several drugs and endogenous substrates has been well documented and may play a significant role in drug disposition and development of various disease states, such as nephrotoxicity and familial idiopathic hypouricemia. Members of this family of transporters have been localized mainly to the renal epithelia of various species. Much of the early research in this field has focused on their role in renal drug transport, yet increasing research on this family of transporters has localized them to various other epithelial tissues, including liver, brain, and placenta. Thus, an understanding of the role of these transporters in drug interaction and disposition in the kidney and other tissues may help in the determination of individual drug response, susceptibility to drug toxicity, and chemical carcinogenesis. This review seeks to summarize current knowledge of the molecular function and substrate profile of cloned organic anion transporters and to discuss recent progress in the understanding of the impact of interindividual variability, transcriptional regulation, and tissue distribution on individual drug response.Keywords
This publication has 101 references indexed in Scilit:
- Genome-wide association study for serum urate concentrations and gout among African Americans identifies genomic risk loci and a novel URAT1 loss-of-function alleleHuman Molecular Genetics, 2011
- The Role of Transporters in the Pharmacokinetics of Orally Administered DrugsPharmaceutical Research, 2009
- Activation of Protein Kinase Cζ Increases OAT1 (SLC22A6)- and OAT3 (SLC22A8)-mediated TransportOnline Journal of Public Health Informatics, 2009
- Mutations in Glucose Transporter 9 Gene SLC2A9 Cause Renal HypouricemiaAmerican Journal of Human Genetics, 2008
- Organic Anion Transporter OAT1 Undergoes Constitutive and Protein Kinase C-regulated Trafficking through a Dynamin- and Clathrin-dependent PathwayOnline Journal of Public Health Informatics, 2008
- Physiology, structure, and regulation of the cloned organic anion transportersXenobiotica, 2008
- Regulation of hepatic bile acid transporters Ntcp and Bsep expressionBiochemical Pharmacology, 2007
- Development and characterization of immobilized human organic anion transporter-based liquid chromatographic stationary phase: hOAT1 and hOAT2Journal of Chromatography B, 2007
- Impaired Clearance of Methotrexate in Organic Anion Transporter 3 (Slc22a8) Knockout Mice: A Gender Specific Impact of Reduced FolatesPharmaceutical Research, 2007
- Determination of the external loops and the cellular orientation of the N- and the C-termini of the human organic anion transporter hOAT1Biochemical Journal, 2006