Rat Kidney Slices for Evaluation of Apical Membrane Transporters in Proximal Tubular Cells.

J Pharm Sci

Faculty of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. Electronic address:

Published: August 2019

AI Article Synopsis

  • Kidney slices have been effectively used to study transport processes in renal tubular epithelial cells, particularly for understanding how substances move in and out of these cells.
  • Recent research has confirmed that key transporters, responsible for both influx and efflux of various compounds, are functional in rat kidney slices, making them a good model for pharmacological studies.
  • The study demonstrates that rat kidney slices can accurately evaluate renal drug disposition linked to transporters on both the apical and basolateral membranes, indicating their potential for preclinical investigations.

Article Abstract

Kidney slice has been often used as a tool reflecting basolateral transport in renal tubular epithelial cells. Recently, we reported that several important apical reabsorptive transporters such as Octn1/2, Sglt1/2, and Pept1/2 were functional in mouse kidney slices as well as transporter activities in basolateral side, which have been well accepted. Because rats are often used for preclinical pharmacodynamic and pharmacokinetic studies as well as mice, it is important to confirm applicability of rat kidney slices for evaluation of apically expressed transporters. The present study investigates usefulness of kidney slices from rats for evaluation of apical membrane transporters for efflux (multidrug resistance 1a, mdr1a) as well as influx (Octn1/2, Sglt1/2, Pept1/2). Na-dependent uptake of ergothioneine (Octn1), carnitine (Octn2), and methyl-α-D-glucopyranoside (Sglt1/2) by rat kidney slices was observed, and the uptake was decreased by selective inhibitors. In addition, uptake of glycyl-sarcosine (Pept1/2) showed H-dependence and was decreased by selective inhibitor. Furthermore, accumulation of mdr1a substrate azasetron was increased in the presence of zosuquidar, an mdr1a inhibitor, while strain differences existed. In conclusion, rat kidney slices should be useful for evaluation of renal drug disposition regulated by transporters in apical as well as basolateral membranes of rat renal proximal tubule cells.

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http://dx.doi.org/10.1016/j.xphs.2019.03.031DOI Listing

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