Kidney organic cations

Okuda, M., et al. cDNA cloning and functional expression of a novel rat kidney organic cation transporter, OCT2. Biochem. Biophys. Res. 

The organic cation transporters (OCTs) facilitate the uptake of many cationic drugs across different barrier membranes from kidney, liver, and intestine... 

Cell lines, such as the Caco-2 and MDCK cells [27, 35, 47, 49, 57, 67, 128-133], have been used frequently to study different transporters in the GI tract. These cell lines have been evaluated for transport both in absorptive and secretory direction and in addition also been transfected with specified transporter systems of interests to yield new clones [23, 31, 72, 79, 80, 134] or co-cultures [135], Some of the uptake transporters belonging to the organic cation transporter (OCT) family have also been identified in cell lines such as the pig kidney cell line LLC-PK1, and MDCK [67, 136]. In fact, its presence in Caco-2 cells needs to be further elucidated as reports have shown both the absence and presence of transporters from this family of transporters [136-138],... 

L. M., Feng, B., Giacomini, K. M., Functional characteristics and steroid hormone-mediated regulation of an organic cation transporter in Madin-Darby Canine Kidney cells, J. Pharmacol. Exp. Ther. 2001, 299, 392— 398. 

Koepsell, H., V. Gorboulev, and P. Arndt. Molecular pharmacology of organic cation transporters in kidney. 

Koepsell, H. Organic cation transporters in intestine, kidney, liver, and brain. Annu. Rev. Physiol. 1998, 60, 243-266. 

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. 

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. 

Y. Urakami, N. Kimura, M. Okuda, and K. Inui. Creatinine transport by basolateral organic cation transporter hOCT2 in the human kidney. Pharm Res 21 976-981... 

S. Masuda, T. Terada, A. Yonezawa, Y. Tanihara, K. Kishimoto, T. Katsura, O. Ogawa, and K. Inui. Identification and functional characterization of a new human kidney-specific H+/organic cation antiporter, kidney-specific multidrug and toxin extrusion 2. J Am Soc Nephrol 17 2127-2135 (2006). 

All four kinds of ABC transporters are found in the kidney and may be involved in the export of some xenobiotics. Also, organic cations can be eliminated by transporters such as the organic cation transporter 2 (OCT2). 

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.

Grundemann D, Babin-Ebell J, Martel F, Ording N, Schmidt A, Schomig E (1997) Primary structure and functional expression of the apical organic cation transporter from kidney epithelial LLC-PK1 cells. J Biol Chem 272, 10408-10413. 

Dutt A, Heath LA, Nelson JA. P-glycoprotein and organic cation secretion by the mammalian kidney. J Pharmacol Exp Ther 1994 269(3) 1254-1260. 

PROCAINAMIDE ANTIBIOTICS - TRIMETHOPRIM Procainamide levels are t by trimethoprim Trimethoprim is a potent inhibitor of organic cation transport in the kidney, and elimination of procainamide is impaired Watch for signs of procainamide toxicity 1 the dose of procainamide, particularly in the elderly... 

CIMETIDINE, RANITIDINE ANTIARRHYTHMICS-AMIODARONE, FLECAINIDE, MEXILETINE, PROCAINAMIDE, PROPAFENONE Likely t plasma concentrations of these antiarrhythmics and risk of adverse effects Cimetidine inhibits CYP2D6-mediated metabolism of flecainide, mexiletine, procainamide and propafenone. Ranitidine is a much weaker CYP2D6 inhibitor. Cimetidine is a potent inhibitor of organic cation transport in the kidney, and the elimination of procainamide is impaired Monitor PR and BP at least weekly until stable. Warn patients to report symptoms of hypotension (lightheadedness, dizziness on standing, etc.). Consider alternative acid suppression therapy... 

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