A clinical drug-drug interaction between famotidine (a H2 receptor antagonist) and probenecid has not been reproduced in rats. The present study hypothesized that the species-dependent probenecid sensitivity is due to a species difference in the contribution of renal organic anion and cation transporters. The transport activities of the H2 receptor antagonists (cimetidine, famotidine, and ranit...

Renal elimination of a number of cationic compounds is thought to be mediated by the organic cation transporter 2 (OCT2, SLC22A2), a drug uptake transporter expressed at the basolateral domain of renal tubular cells. Recently, the key efflux transporter for the secretion organic cations was identified as an electroneutral H(+)/organic cation exchanger termed the multidrug and toxin extrusion (M...

Many organic cations are transported across the apical membrane of the proximal tubule by specific saturable mechanisms. The goal of this study was to determine if the transporter for tetraethylammonium (TEA) in the brush border membrane of an established opossum kidney (OK) cell line is glycosylated and to elucidate the function of this glycosylation. The uptake of TEA was determined in OK cel...

Digoxin is a drug that is commonly used to treat congestive heart failure. Because of digoxin's narrow therapeutic index, patients are susceptible to drug-drug interaction-mediated cardiotoxicity. Digoxin is primarily cleared renally; however, a significant component of clearance is due to multidrug resistance 1-mediated transport into bile. Digoxin is reported to be actively transported into h...

PURPOSE Dopamine has several important functions in the retina including a possible role in controlling photoreceptor disk shedding to the RPE. While some cells express a transporter for dopamine, the RPE cell does not, leading us to ask whether the newly described catecholamine transport system, the extraneuronal monoamine transporter (uptake(2)) (also known as organic cation transporter 3 (OC...

Protein expression of renal uptake and efflux transporters was quantified by quantitative targeted proteomics using the surrogate peptide approach. Renal uptake transporters assessed in this study included organic anion transporters (OAT1-OAT4), organic cation transporter 2 (OCT2), organic/carnitine cation transporters (OCTN1 and OCTN2), and sodium-glucose transporter 2 (SGLT2); efflux transpor...

Pyrethroids are widely-used chemical insecticides, to which humans are commonly exposed, and known to alter functional expression of drug metabolizing enzymes. Limited data have additionally suggested that drug transporters, that constitute key-actors of the drug detoxification system, may also be targeted by pyrethroids. The present study was therefore designed to analyze the potential regulat...

Renal organic cation transporters are downregulated by nitric oxide (NO) in rat endotoxemia. NO generated by inducible NO synthase (iNOS) is substantially increased in the renal cortex after renal ischemia-reperfusion (I/R) injury. Therefore, we investigated the effects of iNOS-specific NO inhibition on the expression of the organic cation transporters rOct1 and rOct2 (Slc22a1 and Slc22a2, resp...