Organic cation transporters renal

Suhre WM, Ekins S, Chang C, Swaan PW and Wright SH. Molecular determinants of substrate/inhibitor binding to the human and rabbit renal organic cation transporters hOCT2 and rbOCT2. Mol Pharmacol 2005 67 1067-77. 

In addition to PepTl, there is a related renal transporter, PepT2. There are also a series of other uptake transporters (organic anion transporting polypeptides, organic anion transporters, organic cation transporters), which are expressed primarily in the liver and other tissues but are not known to affect oral bioavailability. 

Nelson, J. A., Dutt, A., Allen, L. H., Weight, D. A., Functional expression of renal organic cation transporter and P-glycoprotein in Xenopus laevis oocytes, Cancer Chemother. Pharmacol. 1995, 37, 187-189. 

Sweet DH, Miller DS, Pritchard JB. Basolateral localization of organic cation transporter 2 in intact renal proximal tubules. Am J Physiol Renal Physiol 2000 279(5) F826—F834. 

Wang H, Kekuda R, Conway SJ et al. Stmcture, function, and regional distribution of the organic cation transporter OCT3 in the kidney. Am J Physiol Renal Physiol 2000 279(3) F449-F458. 

Alexander, S., Gorboulev, V., Gorbunov, D., Kelley T., Volk, C., Schmitt, B.M., Schlachtbauer, P., Ciarimboli, G., and Koepsell, H. (2007) Identification of cysteines in rat organic cation transporters rOCTl (C322,C451) and rOCT2 (C451) critical for transport activity and substrate affinity. Am. J. Physiol. Renal Physiol, (web preprint, June 13, 2007). 

Takeda M, Khamdang S, Narikawa S, Kimura H, Kobayashi Y, Yamamoto Y, Cha SH, Sekine T, Endou H. Human organic anion transporters and human organic cation transporters mediate renal antiviral transport. J Pharmacol Exp Ther 2002 300 918-924. 

Slitt AL, Cherrington NJ, Hartley DP, et al. Tissue distribution and renal developmental changes in rat organic cation transporter mRNA levels. Drug Metab Dispos 2002 30 212-219. 

Kimura N, Masuda S, Tanihara Y, et al. Metformin is a superior substrate for renal organic cation transporter OCT2 rather than hepatic OCTl. Drug Metab Pharma-cokinet 2005 20 379-386. 

Jonker JW, Wagenaar E, Van Eijl S, et al. Deficiency in the organic cation transporters 1 and 2 (Octl/Oct2 [Slc22al/Slc22a2]) in mice abolishes renal secretion of organic cations. Mol Cell Biol 2003 23 7902-7908. 

Ullrich KJ, Rumrich G, David C, et al. Bisubstrates substances that interact with renal contraluminal organic anion and organic cation transport systems. I. Amines, piperidines, piperazines, azepines, pyridines, quinolines, imidazoles, thiazoles, guanidines and hydrazines. Pflugers Arch 1993 425 280-299. 

Further clinical examples of potential stereoselective renal secretion of organic cations have been recently reported. A major metabolite of verapamil (D-617) is actively secreted by the kidney (59). Upon coadministration of dmetidine, the renal clearance of the S-D-617 isomer was significantly decreased, whereas the clearance of the R-D-617 metabolite was unaffected by dmetidine administration (59). Stereoselective renal secretion was suggested as the mechanism of this effect. However, it is not known if this metabolite is actually secreted by the organic cation transport system. The renal clearance of unbound S(+) disopyramide was... 

R. J. Ott, A. C, Hui, G, Yuan, and K. M. Giacomini, Organic cation transport in human renal brush border membrane vesicles. Am. ]. Physiol., 261 F443-F451 (1991). 

Miyamoto Y,Tiruppathi C, GanapathyV, Eeibach EEI. Multiple transport systems for organic cations in renal brush-border membranes vesicles. Am J Physiol 1989 256 E540-E548. 

FIsyu PFI, Gisclon LG, Flul AC, Giacomini KM. Interactions of organic anions with the organic cation transporter in renal BBMV... 

Ott RJ, Flul C, Glacomlne KM. Mechanisms of interactions between organic anions and the organic cation transporter in renal brush border membrane vesicles. Biochem Pharmacol 1990 40 659-661. 

Lamivudine, a weak inhibitor of organic cation transport by renal tubule epithehal cells [82], has also not been associated with significant nephrotoxicity. 

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