Abstract
Organic anion transporters in renal proximal tubules play essential roles in the reabsorption of endogenous anions such as urate and estron-sulfate as well as in the excretion of metabolites of administered drugs and xenobiotics. Although many organic anion transporters of renal proximal tubules have been identified by molecular cloning studies, there are many issues remained to be clarified. For example, even though the functional activity of cloned transporters has been demonstrated in exogenous expression systems, it is not clear how the detected activity reflects the physiological roles in vivo. To address this issue, we have applied metabolomic analysis on the transporter gene knockout mice. We have used Capillary Electrophoresis-TOFMS in the analysis of the urine of the knockout mice to reveal the physiological role of an orphan transporter of SLC22 organic anion transporter family. Next question to be addressed is that the sum of the functions of single transporter molecules seems not enough to explain physiological function of organic anion transport of renal proximal tubules. We have exploited the idea of transportsome in renal proximal tubules and tried to reveal the molecular complexes composed of cooperating transporters, other functional proteins such as enzymes and regulatory molecules that are assembled by scaffold proteins. We have proposed apical membrane organic anion transportsomes assembled by PDZ proteins. We would like to discuss how it is possible to link the functions of transporter molecules to renal organic anion transport physiology. [J Physiol Sci. 2007;57 Suppl:S61]
