Organic anion transporter (Slc22a) family members as mediators of toxicity.
Exposure of the body to toxic organic anions is unavoidable and occurs from both intentional and unintentional sources. Many hormones, neurotransmitters, and waste products of cellular metabolism, or their metabolites, are organic anions. The same is true for a wide variety of medications, herbicides, pesticides, plant and animal toxins, and industrial chemicals and solvents. Rapid and efficient elimination of these substances is often the body's best defense for limiting both systemic exposure and the duration of their pharmacological or toxicological effects. For organic anions, active transepithelial transport across the renal proximal tubule followed by elimination via the urine is a major pathway in this detoxification process. Accordingly, a large number of organic anion transport proteins belonging to several different gene families have been identified and found to be expressed in the proximal nephron. The function of these transporters, in combination with the high volume of renal blood flow, predisposes the kidney to increased toxic susceptibility. Understanding how the kidney mediates the transport of organic anions is integral to achieving desired therapeutic outcomes in response to drug interactions and chemical exposures, to understanding the progression of some disease states, and to predicting the influence of genetic variation upon these processes. This review will focus on the organic anion transporter (OAT) family and discuss the known members, their mechanisms of action, subcellular localization, and current evidence implicating their function as a determinant of the toxicity of certain endogenous and xenobiotic agents.
Sweet
Douglas H
DH
Department of Pharmaceutical Sciences, Medical University of South Carolina, 280 Calhoun Street (Room QE218), PO Box 250140, Charleston, SC 29425, USA. sweetd@musc.edu
D000818:Animals; D064420:Drug-Related Side Effects and Adverse Reactions / Q000235:genetics*; D006801:Humans; D007668:Kidney / Q000378:metabolism; D027361:Organic Anion Transporters / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004364:Pharmaceutical Preparations / Q000378:metabolism; D014118:Toxins, Biological / Q000378:metabolism
D027361:Organic Anion Transporters; D004364:Pharmaceutical Preparations; D014118:Toxins, Biological