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  1. 原著論文

Imaging of Activity of Multidrug Resistance-Associated Protein 1 in the Lungs

https://repo.qst.go.jp/records/46604
https://repo.qst.go.jp/records/46604
f540c8f2-be3d-473c-8455-9cb9fc8ec2c2
Item type 学術雑誌論文 / Journal Article(1)
公開日 2013-10-16
タイトル
タイトル Imaging of Activity of Multidrug Resistance-Associated Protein 1 in the Lungs
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
アクセス権
アクセス権 metadata only access
アクセス権URI http://purl.org/coar/access_right/c_14cb
著者 Okamura, Toshimitsu

× Okamura, Toshimitsu

WEKO 464576

Okamura, Toshimitsu

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Kikuchi, Tatsuya

× Kikuchi, Tatsuya

WEKO 464577

Kikuchi, Tatsuya

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Okada, Maki

× Okada, Maki

WEKO 464578

Okada, Maki

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Wakizaka, Hidekatsu

× Wakizaka, Hidekatsu

WEKO 464579

Wakizaka, Hidekatsu

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Zhang, Ming-Rong

× Zhang, Ming-Rong

WEKO 464580

Zhang, Ming-Rong

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岡村 敏充

× 岡村 敏充

WEKO 464581

en 岡村 敏充

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菊池 達矢

× 菊池 達矢

WEKO 464582

en 菊池 達矢

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岡田 真希

× 岡田 真希

WEKO 464583

en 岡田 真希

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脇坂 秀克

× 脇坂 秀克

WEKO 464584

en 脇坂 秀克

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張 明栄

× 張 明栄

WEKO 464585

en 張 明栄

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抄録
内容記述タイプ Abstract
内容記述 Multidrug resistance-associated protein 1 (MRP1) transports various xenobiotics and metabolites across cell membranes, and the alteration of MRP1 expression is associated with certain lung diseases. This study sought to examine the feasibility of imaging pulmonary MRP1 activity using 6-bromo-7-[11C]methylpurine ([11C]1). A positron emission tomography study with [11C]1 was performed in wild-type, Mrp1 knockout (KO), and P-glycoprotein/breast cancer resistance protein (Pgp/Bcrp) KO mice. Lung radioactivity in wild-type and Mrp1 KO mice reached a maximum level immediately after the administration of [11C]1. Thereafter, radioactivity rapidly decreased in the lungs of wild-type mice, whereas it was mostly retained in the lungs of Mrp1 KO mice. The kinetics in the lungs of Pgp/Bcrp KO mice was quite similar to that of wild-type mice. Analysis of the chemical form confirmed that radioactive compounds in the lungs of Mrp1 KO mice were nearly completely composed of a glutathione conjugate, a MRP1 substrate, 5 minutes after the intravenous administration of [11C]1. The effect of an MRP1 inhibitor, MK571, on the kinetics of [11C]1 was also examined. Treatment with MK571 delayed the elimination of radioactivity from the lungs, compared with control mice. These results suggest that [11C]1 diffuses into the lung tissue after administration and undergoes conversion into the hydrophilic conjugate, which is then specifically expelled by MRP1. In conclusion, [11C]1 allows for the imaging of in vivo MRP1 activity in lungs.
書誌情報 American Journal of Respiratory Cell and Molecular Biology

巻 49, 号 3, p. 335-340, 発行日 2013-08
ISSN
収録物識別子タイプ ISSN
収録物識別子 1044-1549
DOI
識別子タイプ DOI
関連識別子 10.1165/rcmb.2012-0275ma on april 18, 2013
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