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Gene Ablation of Carnitine/Organic Cation Transporter 1 Reduces Gastrointestinal Absorption of 5-Aminosalicylate in Mice
http://hdl.handle.net/2297/43035
http://hdl.handle.net/2297/430354b49011c-0293-425c-9ece-a698018ea569
| 名前 / ファイル | ライセンス | アクション |
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PH-PR-KATO-Y-774.pdf (668.3 kB)
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| Item type | 学術雑誌論文 / Journal Article(1) | |||||
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| 公開日 | 2017-10-04 | |||||
| タイトル | ||||||
| タイトル | Gene Ablation of Carnitine/Organic Cation Transporter 1 Reduces Gastrointestinal Absorption of 5-Aminosalicylate in Mice | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| 著者 |
Shimizu, Takuya
× Shimizu, Takuya× Kijima, Ai× Masuo, Yusuke× Ishimoto, Takahiro× Sugiura, Tomoko× Takahashi, Saki× Nakamichi, Noritaka× Kato, Yukio |
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| 書誌情報 |
Biological and Pharmaceutical Bulletin 巻 38, 号 5, p. 774-780, 発行日 2015-05-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0918-6158 | |||||
| NCID | ||||||
| 収録物識別子タイプ | NCID | |||||
| 収録物識別子 | AA10885497 | |||||
| DOI | ||||||
| 関連タイプ | isIdenticalTo | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1248/bpb.b15-00109 | |||||
| 出版者 | ||||||
| 出版者 | Pharmaceutical Society of Japan = 日本薬学会 | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | 5-Aminosalicylic acid (5-ASA) is an orally administered therapeutic agent for inflammatory bowel diseases, such as ulcerative colitis and Crohn’s disease. We hypothesized that the absorption of 5-ASA is mediated by the polyspecific carnitine/organic cation transporter (OCTN1/SLC22A4), based on the similarity of chemical structure between 5-ASA and other OCTN1 substrates. Therefore, we examined the involvement of this transporter in the disposition of 5-ASA in vivo by using octn1 gene knockout (octn1−/−) mice. After oral administration of 5-ASA, the plasma concentrations of 5-ASA and its primary metabolite, N-acetyl-5-aminosalicylate (Ac-5-ASA), in octn1−/− mice were much lower than those in wild-type mice. The time required to reach maximum plasma concentration was also delayed in octn1−/− mice. On the other hand, the plasma concentration profiles of both 5-ASA and Ac-5-ASA after intravenous administration of 5-ASA (bolus or infusion) were similar in the two strains. Uptake of 5-ASA from the apical to the basal side of isolated small-intestinal tissues of octn1−/− mice, determined in an Ussing-type chamber, was lower than that in wild-type mice. Further, uptake of 5-ASA in HEK293 cells stably transfected with the OCTN1 gene, assessed as the sum of cell-associated 5-ASA and Ac-5-ASA, was higher than that in HEK293 cells transfected with the vector alone. Overall, these results indicate that OCTN1 is involved, at least in part, in the gastrointestinal absorption of 5-ASA. | |||||
| 権利 | ||||||
| 権利情報 | Copyright © 2015 The Pharmaceutical Society of Japan | |||||
| 著者版フラグ | ||||||
| 出版タイプ | VoR | |||||
| 出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||
| 関連URI | ||||||
| 識別子タイプ | URI | |||||
| 関連識別子 | https://www.jstage.jst.go.jp/browse/bpb | |||||
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| 識別子タイプ | URI | |||||
| 関連識別子 | http://www.pharm.or.jp/ | |||||
