論文 - 詳細
| RRC ID | 42248 |
|---|---|
| 著者 | Honda Y, Ushigome F, Koyabu N, Morimoto S, Shoyama Y, Uchiumi T, Kuwano M, Ohtani H, Sawada Y. |
| タイトル | Effects of grapefruit juice and orange juice components on P-glycoprotein- and MRP2-mediated drug efflux. |
| ジャーナル | Br J Pharmacol |
| 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. |
| 巻・号 | 143(7) |
| ページ | 856-64 |
| 公開日 | 2004-12-1 |
| DOI | 10.1038/sj.bjp.0706008 |
| PII | sj.bjp.0706008 |
| PMID | 15504753 |
| PMC | PMC1575941 |
| MeSH | ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism* Algorithms Antineoplastic Agents, Phytogenic / pharmacokinetics Beverages* Biological Transport, Active / drug effects Caco-2 Cells Calcium Channel Blockers / pharmacology Citrus / chemistry* Cyclosporine / pharmacology Food-Drug Interactions HIV Protease Inhibitors / pharmacokinetics Humans Immunosuppressive Agents / pharmacology Membrane Transport Proteins / genetics Membrane Transport Proteins / metabolism* Multidrug Resistance-Associated Protein 2 Multidrug Resistance-Associated Proteins / genetics Multidrug Resistance-Associated Proteins / metabolism* Plant Extracts / chemistry Propionates / pharmacology Quinolines / pharmacology Saquinavir / pharmacokinetics Transfection Verapamil / pharmacology Vinblastine / pharmacokinetics |
| IF | 7.73 |
| 引用数 | 117 |
| WOS 分野 | PHARMACOLOGY & PHARMACY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | LLC-GA5-CoL150(RCB0871) |