p-Aminohippurate Transport in Rat Renal Brush-Border Membranes. A Potential-Sensitive Transport System and an Anion Exchanger.

Ohoka, Kou; Takano, Mikihisa; Okano, Toshio; Maeda, Sayako; Inui, Kentaro; Hori, Ryohei

doi:10.1248/bpb.16.395

Cited by 39 publications

(34 citation statements)

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“…Brush-border membranes from the intestinal mucosa were prepared as described previously . Renal cortex was isolated and brush-border membranes were obtained by Mg/EGTA precipitation as described previously (Ohoka et al, 1993), with some modifications (Torres et al, 2003). Cytosolic fractions from these same tissues were obtained by ultracentrifugation as described previously (Siekevitz, 1962) in a different set of animals.…”

Section: Methodsmentioning

confidence: 99%

HEPATIC AND EXTRAHEPATIC SYNTHESIS AND DISPOSITION OF DINITROPHENYL-S-GLUTATHIONE IN BILE DUCT-LIGATED RATS

Villanueva

Ruiz²,

Soroka³

et al. 2006

Drug Metab Dispos

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ABSTRACT:The ability of the kidney and small intestine to synthesize and subsequently eliminate dinitrophenyl-S-glutathione (DNP-SG), a substrate for the multidrug resistance-associated proteins (Mrps), was assessed in bile duct-ligated (BDL) rats 1, 7, and 14 days after surgery, using an in vivo perfused jejunum model with simultaneous urine collection. A single i.v. dose of 30 mol/kg b.wt. of 1-chloro-2,4-dinitrobenzene (CDNB) was administered, and its glutathione conjugate DNP-SG and dinitrophenyl cysteinyl glycine derivative, which is the result of ␥-glutamyl-transferase action on DNP-SG, were determined in urine and intestinal perfusate by high-performance liquid chromatography. Intestinal excretion of these metabolites was unchanged at day 1, and decreased at days 7 and 14 (؊39% and ؊33%, respectively) after surgery with respect to shams. In contrast, renal excretion was increased by 114%, 150%, and 128% at days 1, 7, and 14. Western blot studies revealed decreased levels of apical Mrp2 in liver and jejunum but increased levels in renal cortex from BDL animals, these changes being maximal between days 7 and 14. Assessment of expression of basolateral Mrp3 at day 14 postsurgery indicated preserved levels in renal cortex, duodenum, jejunum, distal ileum, and colon. Analysis of expression of glutathione-S-transferases ␣, , and , as well as activity toward CDNB, indicates that formation of DNP-SG was impaired in liver, preserved in intestine, and increased in renal cortex. In conclusion, increased renal tubular conversion of CDNB to DNP-SG followed by subsequent Mrp2-mediated secretion into urine partially compensates for altered liver function in experimental obstructive cholestasis.

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Section: Methodsmentioning

confidence: 99%

HEPATIC AND EXTRAHEPATIC SYNTHESIS AND DISPOSITION OF DINITROPHENYL-S-GLUTATHIONE IN BILE DUCT-LIGATED RATS

Villanueva

Ruiz²,

Soroka³

et al. 2006

Drug Metab Dispos

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“…In contrast, organic anion transporters at the apical membrane of the proximal tubule involved in PAH excretion have been less well characterized. The recently cloned pig kidney Oat V 1 (8) corresponds to the previously characterized apical voltage-dependent PAH transporter (9,10). Furthermore, NPT1 (SLC17A1) might represent the classical apical PAH/organic anion exchanger (9), but definite proof is lacking (11).…”

mentioning

confidence: 99%

“…The recently cloned pig kidney Oat V 1 (8) corresponds to the previously characterized apical voltage-dependent PAH transporter (9,10). Furthermore, NPT1 (SLC17A1) might represent the classical apical PAH/organic anion exchanger (9), but definite proof is lacking (11). The multidrug resistance proteins 2 (MRP2/ABCC2) and 4 (MRP4/ABCC4) are ATP-dependent organic anion transporters, and expression in the kidney is mainly restricted to the proximal tubule apical membrane (12,13,14).…”

mentioning

confidence: 99%

Contribution of Multidrug Resistance Protein 2 (MRP2/ABCC2) to the Renal Excretion of p-aminohippurate (PAH) and Identification of MRP4 (ABCC4) as a Novel PAH Transporter

Smeets¹,

Aubel²,

Wouterse³

et al. 2004

Journal of the American Society of Nephrology

139

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Abstract. p-Aminohippurate (PAH) is the classical substrate used in the characterization of organic anion transport in renal proximal tubular cells. Although basolateral transporters for PAH uptake from blood into the cell have been well characterized, there is still little knowledge on the apical urinary efflux transporters. The multidrug resistance protein 2 (MRP2/ ABCC2) is localized to the apical membrane and mediates ATP-dependent PAH transport, but its contribution to urinary PAH excretion is not known. In this report, we show that renal excretion of PAH in isolated perfused kidneys from wild-type and Mrp2-deficient (TR Ϫ ) rats is not significantly different. Uptake of [14 C]PAH in membrane vesicles expressing two different MRP2 clones isolated from Sf9 and MDCKII cells exhibited a low affinity for PAH (Sf9, 5 Ϯ 2 mM; MDCKII, 2.1 Ϯ 0.6 mM). Human MRP4 (ABCC4), which has recently been localized to the apical membrane, expressed in Sf9 cells had a much higher affinity for PAH (K m ϭ 160 Ϯ 50 M). Various inhibitors of MRP2-mediated PAH transport also inhibited MRP4. Probenecid stimulated MRP2 at low concentrations but had no effect on MRP4; but at high probenecid concentrations, both MRP2 and MRP4 were inhibited. Sulfinpyrazone only stimulated MRP2, but inhibited MRP4. Realtime PCR and Western blot analysis showed that renal cortical expression of MRP4 is approximately fivefold higher as compared with MRP2. MRP4 is a novel PAH transporter that has higher affinity for PAH and is expressed more highly in kidney than MRP2, and may therefore be more important in renal PAH excretion.

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“…Brush-border membranes from the intestinal mucosa were prepared as described previously . Renal cortex was isolated and homogenized, and brush-border membranes were obtained by Mg/EGTA precipitation as described previously (Ohoka et al, 1993), with some modifications (Torres et al, 2003). Jejunum and renal cortex homogenates were alternatively solubilized with Triton X-100 as described previously (Cao et al, 2002).…”

Section: Methodsmentioning

confidence: 99%

Effect of Glucagon-Like Peptide 2 on Hepatic, Renal, and Intestinal Disposition of 1-Chloro-2,4-dinitrobenzene

Villanueva

Perdomo²,

Ruiz³

et al. 2012

Drug Metab Dispos

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ABSTRACT:The ability of the liver, small intestine, and kidney to synthesize and subsequently eliminate dinitrophenyl-S-glutathione (DNP-SG), a substrate for multidrug resistance-associated protein 2 (Mrp2), was assessed in rats treated with glucagon-like peptide 2 (GLP-2, 12 g/100 g b.wt. s.c. every 12 h for 5 consecutive days). An in vivo perfused jejunum model with simultaneous bile and urine collection was used. A single intravenous dose of 30 mol/kg b.wt. 1-chloro-2,4-dinitrobenzene (CDNB) was administered, and its conjugate, DNP-SG, and dinitrophenyl cysteinyl glycine (DNP-CG), resulting from the action of ␥-glutamyltransferase on DNP-SG, were determined in bile, intestinal perfusate, and urine by highperformance liquid chromatography. Tissue content of DNP-SG was also assessed in liver, intestine, and kidneys. Biliary excretion of DNP-SG؉DNP-CG was decreased in GLP-2 rats with respect to controls. In contrast, their intestinal excretion was substantially increased, whereas urinary elimination was not affected. Western blot and real-time polymerase chain reaction studies revealed preserved

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p-Aminohippurate Transport in Rat Renal Brush-Border Membranes. A Potential-Sensitive Transport System and an Anion Exchanger.

Cited by 39 publications

References 0 publications

HEPATIC AND EXTRAHEPATIC SYNTHESIS AND DISPOSITION OF DINITROPHENYL-S-GLUTATHIONE IN BILE DUCT-LIGATED RATS

HEPATIC AND EXTRAHEPATIC SYNTHESIS AND DISPOSITION OF DINITROPHENYL-S-GLUTATHIONE IN BILE DUCT-LIGATED RATS

Contribution of Multidrug Resistance Protein 2 (MRP2/ABCC2) to the Renal Excretion of p-aminohippurate (PAH) and Identification of MRP4 (ABCC4) as a Novel PAH Transporter

Effect of Glucagon-Like Peptide 2 on Hepatic, Renal, and Intestinal Disposition of 1-Chloro-2,4-dinitrobenzene

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