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Biophysical Journal 85:2006-2014 (2003)
© 2003 The Biophysical Society

Kinetic Analysis of Rhodamines Efflux Mediated by the Multidrug Resistance Protein (MRP1)

Chantarawan Saengkhae, Chatchanok Loetchutinat and Arlette Garnier-Suillerot

Laboratoire de Physicochimie Biomoléculaire et Cellulaire, Université Paris Nord, Bobigny, France

Correspondence: Address reprint requests to Prof. A. Garnier-Suillerot, Laboratoire de Physicochimie Biomoléculaire et Cellulaire (LPBC-CSSB UMR CNRS 7033), Université Paris Nord, 74 rue Marcel Cachin, 93017 Bobigny, France. Tel.: 33-14-838-7748; Fax: 33-14-838-7777; E-mail: garnier{at}lpbc.jussieu.fr.

Characterization of rhodamine 123 as functional assay for MDR has been primarily focused on P-glycoprotein-mediated MDR. Several studies have suggested that Rh123 is also a substrate for MRP1. However, no quantitative studies of the MRP1-mediated efflux of rhodamines have, up to now, been performed. Measurement of the kinetic characteristics of substrate transport is a powerful approach to enhancing our understanding of their function and mechanism. In the present study, we have used a continuous fluorescence assay with four rhodamine dyes (rhodamine 6G, tetramethylrosamine, tetramethylrhodamine ethyl ester, and tetramethylrhodamine methyl ester) to quantify drug transport by MRP1 in living GLC4/ADR cells. The formation of a substrate concentration gradient was observed. MRP1-mediated transport of rhodamine was glutathione-dependent. The kinetics parameter, ka = VM/km, was very similar for the four rhodamine analogs but ~10-fold less than the values of the same parameter determined previously for the MRP1-mediated efflux of anthracycline. The findings presented here are the first to show quantitative information about the kinetics parameters for MRP1-mediated efflux of rhodamine dyes.






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