QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Submit a response Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Walle, T. Articles by Walle, U. K. Search for Related Content PubMed PubMed Citation Articles by Walle, T. Articles by Walle, U. K.

SHORT COMMUNICATION

THE ß-D-GLUCOSIDE AND SODIUM-DEPENDENT GLUCOSE TRANSPORTER 1 (SGLT1)-INHIBITOR PHLORIDZIN IS TRANSPORTED BY BOTH SGLT1 AND MULTIDRUG RESISTANCE-ASSOCIATED PROTEINS 1/2

Department of Cell and Molecular Pharmacology and Experimental Therapeutics Medical University of South Carolina Charleston, South Carolina

Phloridzin, a glucoside of the flavonoid-like polyphenol phloretin, has long been known to be a specific nontransportable inhibitor of the sodium-dependent glucose transporter SGLT1. The objective of this study was to determine whether efflux by multidrug resistance-associated protein (MRP) transporters might have masked the absorption by SGLT1 in previous studies. Various cells used as transport models were incubated with phloridzin (50 µM) in the absence and presence of 50 µM 3-[[3-[2-(7-chloroquinolin-2-yl)vinyl]phenyl]-(2-dimethylcarbamoylethylsulfanyl)methylsulfanyl] propionic acid (MK-571), a highly selective MRP1/MRP2 inhibitor, and the cellular uptake of phloridzin was measured by high performance liquid chromatography. The uptake of phloridzin by SGLT1-transfected Chinese hamster ovary (CHO) (G6D3) cells was 1.7-fold higher than that by parent CHO cells (p < 0.01). In the presence of MK-571, the uptake of phloridzin by CHO cells increased 3.7-fold (p < 0.001). MK-571 caused an 8.0-fold increase in the uptake of phloridzin by G6D3 cells (p < 0.0001). Thus, in the absence of MRP1 efflux, transport of phloridzin by SGLT1 was clearly demonstrated. Similar results were obtained for the glycosides of the flavonoids quercetin, genistein, and diosmetin. A significantly lower accumulation of phloridzin in MRP2-transfected Madin-Darby canine kidney (MDCK) cells compared with parent MDCK cells demonstrated that phloridzin was a substrate also for MRP2 (p < 0.05). This conclusion was further strengthened when MK-571 increased the uptake by MRP2-MDCK cells as much as 3.6-fold (p < 0.01). These results demonstrate that phloridzin, in contrast to previous notions, is transported by SGLT1. In addition, they demonstrate that this and other flavonoid glycosides unexpectedly are efficiently effluxed by both MRP1 and MRP2.

This article has been cited by other articles:

				M. L. Olson, M. E. Kargacin, C. A. Ward, and G. J. Kargacin Effects of Phloretin and Phloridzin on Ca2+ Handling, the Action Potential, and Ion Currents in Rat Ventricular Myocytes J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 921 - 929. [Abstract] [Full Text] [PDF]

				O. Kwon, P. Eck, S. Chen, C. P. Corpe, J.-H. Lee, M. Kruhlak, and M. Levine Inhibition of the intestinal glucose transporter GLUT2 by flavonoids FASEB J, February 1, 2007; 21(2): 366 - 377. [Abstract] [Full Text] [PDF]

				P. A. Tsuji and T. Walle Inhibition of benzo[a]pyrene-activating enzymes and DNA binding in human bronchial epithelial BEAS-2B cells by methoxylated flavonoids Carcinogenesis, August 1, 2006; 27(8): 1579 - 1585. [Abstract] [Full Text] [PDF]

				X. Wen and T. Walle Preferential induction of CYP1B1 by benzo[a]pyrene in human oral epithelial cells: impact on DNA adduct formation and prevention by polyphenols Carcinogenesis, October 1, 2005; 26(10): 1774 - 1781. [Abstract] [Full Text] [PDF]

				A. L. A. Sesink, I. C. W. Arts, V. C. J. de Boer, P. Breedveld, J. H. M. Schellens, P. C. H. Hollman, and F. G. M. Russel Breast Cancer Resistance Protein (Bcrp1/Abcg2) Limits Net Intestinal Uptake of Quercetin in Rats by Facilitating Apical Efflux of Glucuronides Mol. Pharmacol., June 1, 2005; 67(6): 1999 - 2006. [Abstract] [Full Text] [PDF]

				T. Walle, A. M. Browning, L. L. Steed, S. G. Reed, and U. K. Walle Flavonoid Glucosides Are Hydrolyzed and Thus Activated in the Oral Cavity in Humans J. Nutr., January 1, 2005; 135(1): 48 - 52. [Abstract] [Full Text] [PDF]

				S. Lesser, R. Cermak, and S. Wolffram Bioavailability of Quercetin in Pigs Is Influenced by the Dietary Fat Content J. Nutr., June 1, 2004; 134(6): 1508 - 1511. [Abstract] [Full Text] [PDF]