D-Malate decreases renal content of α-ketoglutarate, a driving force of organic anion transporters OAT1 and OAT3, resulting in inhibited tubular secretion of phenolsulfonphthalein, in rats

2017 ◽  
Vol 38 (8) ◽  
pp. 479-485 ◽  
Author(s):  
Yuichi Uwai ◽  
Tatsuya Kawasaki ◽  
Tomohiro Nabekura
2012 ◽  
Vol 302 (12) ◽  
pp. F1640-F1649 ◽  
Author(s):  
Maki Nomura ◽  
Hideyuki Motohashi ◽  
Hiroko Sekine ◽  
Toshiya Katsura ◽  
Ken-ichi Inui

Organic anion transporters (OAT1 and OAT3) and multidrug resistance-associated proteins (MRP2 and MRP4) play important roles in anionic drug secretion in renal proximal tubules. Changes in the expression of such transporters are considered to affect the tubular secretion of anionic drugs. The purpose of this study was to elucidate the developmental changes in the expression of OAT1, OAT3, MRP2, and MRP4 and their effects on the tubular secretion of drugs. The mRNA level of each transporter was measured by real-time PCR, and the protein expression was evaluated by Western blotting and immunohistochemical analysis. In addition, the tubular secretion of phenolsulfonphthalein (PSP) in infant (postnatal day 14) and adult rats was estimated based on in vivo clearance study. The protein expression of organic anion transporters were very low at postnatal day 0 and gradually increased with age. In postnatal day 14 rats, the expression of OAT1 and OAT3 seemed to be at almost mature levels, while MRP2 and MRP4 seemed to be at immature levels. Immunohistochemical analysis in the kidney of postnatal day 0 rats revealed OATs on the basolateral membrane and MRPs on the brush-border membrane. At postnatal day 0, the distribution of these transporters was restricted to the inner cortical region, while after postnatal day 14, it was identical to that in adult kidney. An in vivo clearance study revealed that the tubular secretion of PSP was significantly lower in postnatal day 14 rats than adult rats. These results indicate that age-dependent changes in organic anion transporter expression affect the tubular secretion of anionic drugs in pediatric patients.


2000 ◽  
Vol 279 (2) ◽  
pp. F216-F232 ◽  
Author(s):  
Rémon A. M. H. Van Aubel ◽  
Rosalinde Masereeuw ◽  
Frans G. M. Russel

Renal organic anion transport systems play an important role in the elimination of drugs, toxic compounds, and their metabolites, many of which are potentially harmful to the body. The renal proximal tubule is the primary site of carrier-mediated transport from blood to urine of a wide variety of anionic substrates. Recent studies have shown that organic anion secretion in renal proximal tubule is mediated by distinct sodium-dependent and sodium-independent transport systems. Knowledge of the molecular identity of these transporters and their substrate specificity has increased considerably in the past few years by cloning of various carrier proteins. However, a number of fundamental questions still have to be answered to elucidate the participation of the cloned transporters in the overall tubular secretion of anionic xenobiotics. This review summarizes the latest knowledge on molecular and pharmacological properties of renal organic anion transporters and homologs, with special reference to their nephron and plasma membrane localization, transport characteristics, and substrate and inhibitor specificity. A number of the recently cloned transporters, such as the p-aminohippurate/dicarboxylate exchanger OAT1, the anion/sulfate exchanger SAT1, the peptide transporters PEPT1 and PEPT2, and the nucleoside transporters CNT1 and CNT2, are key proteins in organic anion handling that possess the same characteristics as has been predicted from previous physiological studies. The role of other cloned transporters, such as MRP1, MRP2, OATP1, OAT-K1, and OAT-K2, is still poorly characterized, whereas the only information that is available on the homologs OAT2, OAT3, OATP3, and MRP3–6 is that they are expressed in the kidney, but their localization, not to mention their function, remains to be elucidated.


2016 ◽  
Vol 468 (11-12) ◽  
pp. 1909-1918 ◽  
Author(s):  
Birgitta C. Burckhardt ◽  
Maja Henjakovic ◽  
Yohannes Hagos ◽  
Gerhard Burckhardt

2015 ◽  
Vol 43 (12) ◽  
pp. 1855-1863 ◽  
Author(s):  
Wei Wu ◽  
Kevin T. Bush ◽  
Henry C. Liu ◽  
Christopher Zhu ◽  
Ruben Abagyan ◽  
...  

ACS Omega ◽  
2021 ◽  
Vol 6 (6) ◽  
pp. 4347-4354
Author(s):  
Tatsuya Kawasaki ◽  
Masaki Kondo ◽  
Rioka Hiramatsu ◽  
Tomohiro Nabekura

2020 ◽  
Vol 472 (6) ◽  
pp. 711-719 ◽  
Author(s):  
Evangelina Cecilia Nosetto ◽  
Romina Valeria Campagno ◽  
Adriana Mónica Torres ◽  
Anabel Brandoni

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