caa a22 4500 445314001 CHVBK 20180317142639.0 cr unu---uuuuu 170323e20110501xx s 000 0 eng 10.1007/s11095-010-0348-7 doi (NATIONALLICENCE)springer-10.1007/s11095-010-0348-7 Effects of Metabolic Acidosis on Expression Levels of Renal Drug Transporters [Elektronische Daten] [Arong Gaowa, Hideyuki Motohashi, Toshiya Katsura, Ken-ichi Inui] ABSTRACT: Purpose: In the renal proximal tubular cells, various transporters play important roles in the secretion and reabsorption of drugs. When metabolic acidosis is induced, a number of adaptive changes occur in the kidney. The purpose of this study was to clarify the changes of drug transporters under the acidosis and the effects of these changes on urinary drug excretion. Methods: Wistar/ST rats were given 1.5% NH4Cl in tap water for 48h to induce the acidosis. Pharmacokinetics of PSP or metformin was evaluated. In addition, expression levels of drug transporters were examined by Western Blotting. Results: The renal clearance of PSP was markedly decreased, whereas the creatinine clearance and renal clearance of metformin were unchanged. Furthermore, Western blots indicated that the protein expression level of organic anion transporter (OAT) 3 was decreased. In contrast to OAT3 levels, OAT1 and organic cation transporter (OCT) 2 levels were unaffected. An immunohistochemical analysis showed that the OAT3 protein in the proximal tubules was localized in the basolateral membrane both of the normal and the acidosis rats. Conclusion: The decrease of renal excretion of anionic drugs during metabolic acidosis might be partly due to a reduction in the level of OAT3 protein. Springer Science+Business Media, LLC, 2010 acidosis nationallicence anion nationallicence kidney nationallicence secretion nationallicence transporter nationallicence Gaowa Arong Department of Pharmacy, Kyoto University Hospital Faculty of Medicine, Kyoto University, Sakyo-ku, 606-8507, Kyoto, Japan aut Motohashi Hideyuki Department of Pharmacy, Kyoto University Hospital Faculty of Medicine, Kyoto University, Sakyo-ku, 606-8507, Kyoto, Japan aut Katsura Toshiya Department of Pharmacy, Kyoto University Hospital Faculty of Medicine, Kyoto University, Sakyo-ku, 606-8507, Kyoto, Japan aut Inui Ken-ichi Department of Pharmacy, Kyoto University Hospital Faculty of Medicine, Kyoto University, Sakyo-ku, 606-8507, Kyoto, Japan aut Pharmaceutical Research Springer US; http://www.springer-ny.com 28/5(2011-05-01), 1023-1030 0724-8741 28:5<1023 2011 28 11095 https://doi.org/10.1007/s11095-010-0348-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s11095-010-0348-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Gaowa Arong Department of Pharmacy, Kyoto University Hospital Faculty of Medicine, Kyoto University, Sakyo-ku, 606-8507, Kyoto, Japan aut NATIONALLICENCE 700 1- Motohashi Hideyuki Department of Pharmacy, Kyoto University Hospital Faculty of Medicine, Kyoto University, Sakyo-ku, 606-8507, Kyoto, Japan aut NATIONALLICENCE 700 1- Katsura Toshiya Department of Pharmacy, Kyoto University Hospital Faculty of Medicine, Kyoto University, Sakyo-ku, 606-8507, Kyoto, Japan aut NATIONALLICENCE 700 1- Inui Ken-ichi Department of Pharmacy, Kyoto University Hospital Faculty of Medicine, Kyoto University, Sakyo-ku, 606-8507, Kyoto, Japan aut NATIONALLICENCE 773 0- Pharmaceutical Research Springer US; http://www.springer-ny.com 28/5(2011-05-01), 1023-1030 0724-8741 28:5<1023 2011 28 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer