Effects of grapefruit juice and orange juice components on P-glycoprotein- and MRP2-mediated drug efflux

Yoko Honda, Fumihiko Ushigome, Noriko Koyabu, Satoshi Morimoto, Yukihiro Shoyama, Takeshi Uchiumi, Michihiko Kuwano, Hisakazu Ohtani, Yasufumi Sawada

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123 Citations (Scopus)

Abstract

1 We investigated the effects of grapefruit juice (GFJ) and orange juice (OJ) on drug transport by MDR1 P-glycoprotein (P-gp) and multidrug resistance protein 2 (MRP2), which are efflux transporters expressed in human small intestine. 2 We examined the transcellular transport and uptake of [ 3H]vinblastine (VBL) and [ 14C]saquinavir in a human colon carcinoma cell line (Caco-2) and in porcine kidney epithelial cell lines transfected with human MDR1 cDNA and human MRP2 cDNA, LLC-GA5-COL150, and LLC-MRP2, respectively. 3 In Caco-2 cells, the basal-to-apical transports of [ 3H]VBL and [ 14C]saquinavir were greater than those in the opposite direction. The ratio of basal-to-apical transport to apical-to-basal transport of [ 3H]VBL and [ 14C]saquinavir by Caco-2 cells was reduced in the presence of MK571 (MRPs inhibitor), verapamil (P-gp inhibitor), cyclosporin A (inhibitor of both), 50% ethyl acetate extracts of GFJ and OJ, or their components (6′,7′-dihydroxybergamottin, bergamottin, tangeretin, hepatomethoxyflavone, and nobiletin). 4 Studies of transport and uptake of [ 3H]VBL and [ 14C]saquinavir with MDR1 and MRP2 transfectants showed that VBL and saquinavir are transported by both P-gp and MRP2. GFJ and OJ components inhibited the transport by MRP2 as well as P-gp. However, their inhibitory potencies for P-gp or MRP2 were substrate-dependent. 5 The present study has revealed that GFJ and OJ interact with not only P-gp but also MRP2, both of which are expressed at apical membranes and limit the apical-to-basal transport of VBL and saquinavir in Caco-2 cells.

Original languageEnglish
Pages (from-to)856-864
Number of pages9
JournalBritish Journal of Pharmacology
Volume143
Issue number7
DOIs
Publication statusPublished - 2004 Dec 1
Externally publishedYes

Keywords

  • Furanocoumarins
  • Grapefruit juice
  • MDR1
  • MRP2
  • Orange juice
  • P-glycoprotein
  • Polymethoxyflavones
  • Saquinavir
  • Transport
  • Vinblastine

ASJC Scopus subject areas

  • Pharmacology

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  • Cite this

    Honda, Y., Ushigome, F., Koyabu, N., Morimoto, S., Shoyama, Y., Uchiumi, T., Kuwano, M., Ohtani, H., & Sawada, Y. (2004). Effects of grapefruit juice and orange juice components on P-glycoprotein- and MRP2-mediated drug efflux. British Journal of Pharmacology, 143(7), 856-864. https://doi.org/10.1038/sj.bjp.0706008