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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Ohtani, Hisakazu Honda, Yoko Kuwano, Michihiko Sawada, Yasufumi Ushigome, Fumihiko Morimoto, Satoshi Shoyama, Yukihiro Uchiumi, Takeshi Koyabu, Noriko |
| Description | Author Affiliation: Honda Y ( Department of Medico-Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.) |
| Abstract | 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. We examined the transcellular transport and uptake of [(3)H]vinblastine (VBL) and [(14)C]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. In Caco-2 cells, the basal-to-apical transports of [(3)H]VBL and [(14)C]saquinavir were greater than those in the opposite direction. The ratio of basal-to-apical transport to apical-to-basal transport of [(3)H]VBL and [(14)C]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). Studies of transport and uptake of [(3)H]VBL and [(14)C]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. 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. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 7 |
| Volume Number | 143 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2004-12-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Beverages Citrus Chemistry Membrane Transport Proteins Metabolism Multidrug Resistance-Associated Proteins P-Glycoprotein Algorithms Antineoplastic Agents, Phytogenic Pharmacokinetics Biological Transport, Active Drug Effects Caco-2 Cells Calcium Channel Blockers Pharmacology Cyclosporine Food-Drug Interactions HIV Protease Inhibitors Immunosuppressive Agents Genetics Plant Extracts Propionates Quinolines Saquinavir Transfection Verapamil Vinblastine |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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