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Genetic deficiency of carnitine/organic cation transporter 2 (slc22a5) is associated with altered tissue distribution of its substrate pyrilamine in mice
http://hdl.handle.net/2297/20401
http://hdl.handle.net/2297/204015d669281-7045-4fa7-b6d8-860b6ddc89de
| 名前 / ファイル | ライセンス | アクション |
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PH-PR-KATO-Y-495.pdf (638.0 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 | Genetic deficiency of carnitine/organic cation transporter 2 (slc22a5) is associated with altered tissue distribution of its substrate pyrilamine 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 |
Kato, Sayaka
× Kato, Sayaka× Kato, Yukio× Nakamura, Tadakatsu× Sugiura, Tomoko× Kubo, Yoshiyuki× Deguchi, Yoshiharu× Tsuji, Akira |
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| 提供者所属 | ||||||
| 内容記述タイプ | Other | |||||
| 内容記述 | 金沢大学医薬保健研究域薬学系 | |||||
| 書誌情報 |
Biopharmaceutics and Drug Disposition 巻 30, 号 9, p. 495-507, 発行日 2009-10-01 |
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| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 0142-2782 | |||||
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| 収録物識別子タイプ | NCID | |||||
| 収録物識別子 | AA00110161 | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1002/bdd.681 | |||||
| 出版者 | ||||||
| 出版者 | Wiley-Blackwell | |||||
| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Carnitine/organic cation transporter 2 (OCTN2) recognizes various cationic compounds as substrates in vitro, but information on its pharmacokinetic role in vivo is quite limited. This paper demonstrates altered tissue distribution of the OCTN2 substrate pyrilamine in juvenile visceral steatosis (jvs) mice, which have a hereditary defect of the octn2 gene. At 30 min after intravenous injection of pyrilamine, the tissue-to-plasma concentration ratio (K p) in the heart and pancreas was higher, whereas the Kp in kidney and testis was lower in jvs mice compared with wild-type mice. Pyrilamine transport studies in isolated heart slices confirmed higher accumulation, together with lower efflux, of pyrilamine in the heart of jvs mice. The higher accumulation in heart slices of jvs mice was abolished by lowering the temperature, by increasing the substrate concentration, and in the presence of other H1 antagonists or another OCTN2 substrate, carnitine, suggesting that OCTN2 extrudes pyrilamine from heart tissue. On the other hand, the lower distribution to the kidney of jvs mice was probably due to down-regulation of a basolateral transporter coupled with OCTN2, because, in jvs mice, (i) the Kp of pyrilamine in kidney assessed immediately after intravenous injection (∼1 min) was also lower, (ii) the urinary excretion of pyrilamine was lower, and (iii) the uptake of pyrilamine in kidney slices was lower. The renal uptake of pyrilamine was saturable (K m∼236 μM) and was strongly inhibited by cyproheptadine, astemizole, ebastine and terfenadine. The present study thus indicates that genetic deficiency of octn2 alters pyrilamine disposition tissue-dependently. Copyright © 2009 John Wiley & Sons, Ltd. | |||||
| 著者版フラグ | ||||||
| 出版タイプ | AM | |||||
| 出版タイプResource | http://purl.org/coar/version/c_ab4af688f83e57aa | |||||
