» Articles » PMID: 22841915

Drug Transport by Organic Anion Transporters (OATs)

Overview
Journal Pharmacol Ther
Specialty Pharmacology
Date 2012 Jul 31
PMID 22841915
Citations 116
Authors
Affiliations
Soon will be listed here.
Abstract

Common to all so far functionally characterized Organic Anion Transporters (OATs) is their broad substrate specificity and their ability to exchange extracellular against intracellular organic anions. Many OATs occur in renal proximal tubules, the site of active drug secretion. Exceptions are murine Oat6 (nasal epithelium), human OAT7 (liver), and rat Oat8 (renal collecting ducts). In human kidneys, OAT1, OAT2, and OAT3 are localized in the basolateral membrane, and OAT4, OAT10, and URAT1 in the apical cell membrane of proximal tubule cells, respectively. In rats and mice, Oat1 and Oat3 are located basolaterally, and Oat2, Oat5, Oat9, Oat10, and Urat1 apically. Several classes of drugs interact with human OAT1-3, including ACE inhibitors, angiotensin II receptor antagonists, diuretics, HMG CoA reductase inhibitors, β-lactam antibiotics, antineoplastic and antiviral drugs, and uricosuric drugs. For most drugs, interaction was demonstrated in vitro by inhibition of OAT-mediated transport of model substrates; for some drugs, transport by OATs was directly proven. Based on IC₅₀ values reported in the literature, OAT1 and OAT3 show comparable affinities for diuretics, cephalosporins, and nonsteroidal anti-inflammatory drugs whereas OAT2 has a lower affinity to most of these compounds. Drug-drug interactions at OAT1 and OAT3 may retard renal drug secretion and cause untoward effects. OAT4, OAT10, and URAT1 in the apical membrane contribute to proximal tubular urate absorption, and OAT10 to nicotinate absorption. OAT4 is in addition able to release drugs, e.g. diuretics, into the tubule lumen.

Citing Articles

Potential Interaction of Pinocembrin with Drug Transporters and Hepatic Drug-Metabolizing Enzymes.

Sangkapat S, Boonnop R, Pimta J, Chabang N, Nutho B, Jutabha P Pharmaceuticals (Basel). 2025; 18(1).

PMID: 39861105 PMC: 11768629. DOI: 10.3390/ph18010042.


Drug-Induced Hypouricemia.

Ben Salem C, Agrebi M, Sahnoun D, Fathallah N, Hmouda H Drug Saf. 2024; 48(2):129-142.

PMID: 39289314 DOI: 10.1007/s40264-024-01485-7.


The Competitive Counterflow Assay for Identifying Drugs Transported by Solute Carriers: Principle, Applications, Challenges/Limits, and Perspectives.

Fardel O, Moreau A, Carteret J, Denizot C, Le Vee M, Parmentier Y Eur J Drug Metab Pharmacokinet. 2024; 49(5):527-539.

PMID: 38958896 DOI: 10.1007/s13318-024-00902-7.


Case analysis of hepatotoxicity caused by vancomycin.

Wu J, Zhou Y J Med Case Rep. 2024; 18(1):267.

PMID: 38831463 PMC: 11149228. DOI: 10.1186/s13256-024-04574-4.


Evaluation of 14 PFAS for permeability and organic anion transporter interactions: Implications for renal clearance in humans.

Ryu S, Yamaguchi E, Modaresi S, Agudelo J, Costales C, West M Chemosphere. 2024; 361:142390.

PMID: 38801906 PMC: 11774580. DOI: 10.1016/j.chemosphere.2024.142390.