Organic ion transporter

Williams, P.D. and Hottendorf, G.H. (1985). Effects of cw-dichlorodiamineplatinum-II (Cisplatin) on organic ion transport in membrane vesicles from rat kidney cortex. Cancer Treat. Rep. 69 875-880. 

H. Motohashi, Y. Uwai, K. Hiramoto, M. Okuda, and K. Inui. Different transport properties between famotidine and cimetidine by human renal organic ion transporters (SLC22A). Eur J Pharmacol 503 25-30 (2004). 

In vitro stndies have shown that there are distinct transport systems for both baso-lateral and apical uptake of nicotine (Takami et al. 1998). Nicotine has been shown to be actively transported by kidney cells, most likely by the organic ion transporter OCT2 (Zevin et al. 1998 Urakami et al. 1998). Cimetidine decreases renal clearance of nicotine by 47% in nonsmoking volunteers (Bendayan et al. 1990). This is consistent with the inhibition of basolateral uptake by cimetidine detected in vitro. Mecamylamine reduces renal clearance of nicotine in smokers dosed with intra-venons nicotine when urine is alkalinized, but not when nrine is acidified (Zevin et al. 2000). 

Berndt WO, Mehendale HM. 1979. Effects of hexachlorobutadiene (HCBD) on renal function and renal organic ion transport in the rat. Toxicology 14 55-65. 

Cephaloridine will inhibit organic ion transport in the kidney and, this is preceded by the lipid peroxidation. Antioxidants block both events, suggesting that they are related. GSH depletion is a very early event, occurring before lipid peroxidation is detectable. 

You G. The role of organic ion transporters in drug disposition an update. Curr Drug Metab. 2004 5 ... 

Motohashi H, Sakurai Y, Saito H, Masuda S, Urakami Y, Goto M, Fukatsu A, Ogawa O, Inui K. Gene expression levels and immunolocalization of organic ion transporters in the human kidney. J Am Soc Nephrol 2002 13 866-874. 

In vitro exposure of renal cortical slices to cephaloridine results in time- and concentration-dependent increases in lipid peroxidation, as reflected by malondial-dehyde production. Furthermore, the onset of cephaloridine-induced malondial-dehyde production preceded cephaloridine-induced inhibition of organic ion accumulation, suggesting that cephaloridine-induced lipid peroxidation mediates the effects of cephaloridine on organic ion transport. Additionally, antioxidants (e.g., promethazine, N, A -diphenyl-p-phenylenediamine) block the effects of cephaloridine on lipid peroxidation and on organic ion transport, suggesting a cause-effect relationship between cephaloridine-induced lipid peroxidation and inhibition of organic ion transport. 

H. N. Christensen, Organic ion transport during seven decades The amino adds, Biochim. Biophys. Acta, 779 255-269 (1984). 

The transport mechanisms of the organic ion transport systems have been characterized at both membrane sides of proximal tubule, mainly by studies in brush-border and basolateral membranes purified from homogenates of renal cortex. Since a detailed review and a critical discussion of the present knowledge in this field was pubfished by Pritchard [44], only the main conclusions are summarized here. 

Sokol PP. Effect of DQ-2556, a new cephalosporin, on organic ion transport in renal plasma membrane vesicles from the dog, rabbit and rat. J Pharmacol ExpTher 1990 255 436-441. 

Griffiths DA, Flail SD, Sokol PP. Interaction of 3 -azido-3 -deoxythymidine with organic ion transport in rat renal basolateral membrane vesicles. J Pharmacol ExpTher 1991 257 149-155. 

Williams PD, Hitchcock MJ, Hottendorf GH. Effect of cephalosporins on organic ion transport in renal membrane vesicles from the rat and rabbit kidney cortex. Res Commun Chem Pathol Pharmacol 1985 47(3) 357-371. 

Slc22/Organic Ion Transporter Family. Few studies have reported the induction of Slc22a genes by PXR activators. By using rat hepatoma RL-34 cells, cultured primary rat hepatocytes and animals, it was shown that PCN induced the expression of rat hepatic Octl (Slc22al) mRNA. Induction of Octl transporter activity was further demonstrated ex vivo by increased uptake of the prototypical substrate MPP+ into hepatocytes, which were isolated from PCN-treated rats, compared to cells, which were isolated from control animals and in vivo by an increase in biliary excretion of TEA in PCN-treated rats [130]. 

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