Kidneys organic anion/cation transporter

Dresser MJ, Leabman MK, Giacomini KM. Transporters involved in the elimination of drugs in the kidney organic anion transporters and organic cation transporters. J Pharm Sci 2001 90(4) 397-421. 

Dresser, M. J., Leabman, M. K, and Giacomini, K. M. Transporters involved in the elimination of drugs in the kidney Organic anion transporters and organic cation transporters [Review]. Journal of Pharmaceutical Sciences 90(4), 397-421. 2001. Berkhin, E. B. and Flumphreys, M. FI. Regulation of renal tubular secretion of organic compounds [Review]. Kidney International 59, 17-30. 2001. 

Transporters Involved in the Elimination of Drugs in the Kidney Organic Anion Transporters and Organic Cation Transporters. 

Lee, J., Hollyer, R., Rodelas, R., Preuss, H. G., The influence of trimethoprim, sulfamethoxazole, and creatinine on renal organic anion and cation transport in rat kidney tissue, Toxicol. Appl. Pharmacol. 1981, 58, 184-193. 

The kidneys are susceptible to toxicity from xenobiotics (Fig. 7.1) because they too have a high blood flow. Cells of the tubular nephron face double-sided exposure, to agents in the blood on the basolateral side and in the Altered urine on the luminal side. Proximal tubule cells are generally the site of nephrotoxicity, since these cells have an abundance of cytochrome P450 and can transport organic anions and cations from the blood into the cells, thereby concentrating these chemicals manyfold. 

Membrane transporter proteins (MDR or ABC transporter proteins) such as p-glycoprotein are crucially important in the process of excretion and also in absorption and distribution and elimination of chemicals from cells. These transport organic anions or cations and neutral compounds across membranes, pump unwanted chemicals out of cells such as in gut, placenta, and brain, transport chemicals into bile from liver cells, and facilitate excretion from the kidney. 

Figure 7.35 The uptake and elimination of cephaloridine by proximal tubular cells in the kidney and possible mechanisms of toxicity. The uptake can be inhibited (probenicid) and the elimination also inhibited (mepiphenidol). Abbreviations OAT 1, organic anion transporter OCT, organic cation transporter ROS, reactive oxygen species.

Ullrich KJ. Specificity of transporters for organic anions and organic cations in the kidney. Biochim Biophys Acta 1994 1197 45-62. 

Ullrich KJ, Rumrich G, Kloss S. Contralumlnal organic anion and cation transport in the proximal renal tubule V. Interaction with sulfamoyl- and phemoxy diuretics, and with p-lactam antibiotics. Kidney Int 1989 36(1) 78-88. 

Many metabolites produced by hepatic metabolism are eliminated into the intestinal tract via the bile. These metabolites may be excreted in feces but are often reabsorbed. Organic anions (i.e. glucuronides) and cations are actively transported into bile by carrier systems that are similar to those in the renal tubules. Similarly, charged ions can compete for transport by these systems because both are non-selective. Steroidal and related substances are transported by a third carrier mechanism. Glucuronide-conjugated metabolites undergo extensive enterohepatic recirculation— a cycle of absorption from the gastrointestinal tract, metabolism in the liver and excretion in bile—and this cycle delays elimination when the final step in elimination from the body is via the kidneys. 

For example, some SLC on the sinusoidal (basolateral) membrane of hepatocytes take up organic anions, while the ABC on the apical membranes of bile canicular cells excrete them. The combined activities of these two transporters thus results in the vectorial transport of drugs from the blood to the bile. Similarly, the basolateral transporters of the kidney tubular cells act in a coordinated, vectorial manner with apical transporters to secrete organic cations (OCs) from the blood to the urine. 

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