論文 - 詳細
| RRC ID | 61151 |
|---|---|
| 著者 | Nakai Y, Inoue K, Abe N, Hatakeyama M, Ohta KY, Otagiri M, Hayashi Y, Yuasa H. |
| タイトル | Functional characterization of human proton-coupled folate transporter/heme carrier protein 1 heterologously expressed in mammalian cells as a folate transporter. |
| ジャーナル | J Pharmacol Exp Ther |
| Abstract |
The functional characteristics of human proton coupled folate transporter (hPCFT)/heme carrier protein (HCP) 1 were investigated. hPCFT/HCP1 expressed transiently in human embryonic kidney 293 cells mediated the transport of folate at an acidic extracellular pH of 5.5 in a manner independent of Na(+) and insensitive to membrane potential, but its transport activity was absent at near-neutral pH. Folate transport mediated by hPCFT/hHCP1 at pH 5.5 was saturable with a K(m) of 1.67 microM and extensively inhibited by reduced folates, such as folinate, 5-methyltetrahydrofolate, and methotrexate (MTX). Sulfobro-mophthalein and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid were also found to be potent inhibitors of hPCFT/hHCP1, but hemin was found to exhibit only minimal inhibitory effect. When expressed stably as a protein fused with green fluorescent protein (GFP-hPCFT/HCP1) in MDCKII cells, GFP-hPCFT/HCP1 was mainly localized at the apical membrane, and the cellular accumulation of MTX was higher from the apical side than from the basal side. These functional features of hPCFT/HCP1 are consistent with those of the well characterized carrier-mediated folate transport system in the small intestine, suggesting that hPCFT/HCP1 is responsible for the intestinal absorption of folate and also MTX. We also found that sulfasalazine is a potent inhibitor of hPCFT/HCP1, which would interfere with the intestinal absorption of MTX when coadministered in therapy for rheumatoid arthritis as well as folate. |
| 巻・号 | 322(2) |
| ページ | 469-76 |
| 公開日 | 2007-8-1 |
| DOI | 10.1124/jpet.107.122606 |
| PII | jpet.107.122606 |
| PMID | 17475902 |
| MeSH | Animals Anti-Inflammatory Agents, Non-Steroidal / pharmacology Antirheumatic Agents / pharmacology Biological Transport, Active / drug effects Cell Line Cell Membrane / chemistry Cell Membrane / metabolism Diclofenac / pharmacology Dose-Response Relationship, Drug Folic Acid / analogs & derivatives Folic Acid / metabolism* Green Fluorescent Proteins / genetics Green Fluorescent Proteins / metabolism Humans Hydrogen-Ion Concentration Indomethacin / pharmacology Kinetics Membrane Transport Proteins / genetics Membrane Transport Proteins / metabolism Membrane Transport Proteins / physiology* Methotrexate / metabolism* Microscopy, Confocal Nigericin / pharmacology Proton-Coupled Folate Transporter Sulfasalazine / pharmacology Transfection |
| IF | 3.561 |
| 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 | Wikipedia |
| 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 | |
| 遺伝子材料 | pCI-neo-hPCFT (RDB18230) |