Renal Organic Anion Transporters (SLC22 Family): Expression, Regulation, Roles in Toxicity, and Impact on Injury and Disease
Journal Title: The AAPS Journal - Year 2013, Vol 15, Issue 1
Abstract
Organic solute flux across the basolateral and apical membranes of renal proximal tubule cells is a key process for maintaining systemic homeostasis. It represents an important route for the elimination of metabolic waste products and xenobiotics, as well as for the reclamation of essential compounds. Members of the organic anion transporter (OAT, SLC22) family expressed in proximal tubules comprise one pathway mediating the active renal secretion and reabsorption of organic anions. Many drugs, pesticides, hormones, heavy metal conjugates, components of phytomedicines, and toxins are OAT substrates. Thus, through transporter activity, the kidney can be a target organ for their beneficial or detrimental effects. Detailed knowledge of the OATs expressed in the kidney, their membrane targeting, substrate specificity, and mechanisms of action is essential to understanding organ function and dysfunction. The intracellular processes controlling OAT expression and function, and that can thus modulate kidney transport capacity, are also critical to this understanding. Such knowledge is also providing insight to new areas such as renal transplant research. This review will provide an overview of the OATs for which transport activity has been demonstrated and expression/function in the kidney observed. Examples establishing a role for renal OATs in drug clearance, food/drug–drug interactions, and renal injury and pathology are presented. An update of the current information regarding the regulation of OAT expression is also provided.
Authors and Affiliations
Li Wang, Douglas H. Sweet
Keywords
Related Articles
- EP ID EP681768
- DOI 10.1208/s12248-012-9413-y
- Views 80
- Downloads 0
Performance Comparison of Various Maximum Likelihood Nonlinear Mixed-Effects Estimation Methods for Dose–Response Models
The online version of this article (doi:10.1208/s12248-012-9349-2) contains supplementary material, which is available to authorized users.
Applying Biopharmaceutical Classification System (BCS) Criteria to Predict Oral Absorption of Drugs in Dogs: Challenges and Pitfalls
The Biopharmaceutical Classification System (BCS) has been a prognostic tool for assessing the potential effects of formulation on the human drug oral bioavailability. When used in conjunction with in vitro dissolution t...
Challenges in Development of Nanoparticle-Based Therapeutics
In recent years, nanotechnology has been increasingly applied to the area of drug development. Nanoparticle-based therapeutics can confer the ability to overcome biological barriers, effectively deliver hydrophobic drugs...
Addressing the Challenges of Low Clearance in Drug Research
As a result of high-throughput ADME screening, early metabolite identification, and exploration of novel chemical entities, low-intrinsic-clearance compounds continue to increase in drug discovery portfolios. Currently a...
Pharmacokinetics of Levodopa, Carbidopa, and 3-O-Methyldopa Following 16-hour Jejunal Infusion of Levodopa-Carbidopa Intestinal Gel in Advanced Parkinson’s Disease Patients
Motor complications of Parkinson’s disease (PD) are a consequence of pulsatile dopaminergic stimulation from standard oral levodopa therapy. Levodopa–carbidopa intestinal gel (LCIG) is infused continuousl...