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  1. C100 医学部/医学系研究科
  2. C100d 学位論文
  3. 博士論文(医博・論医博)

Nongenomic Effects of Fluticasone Propionate and Budesonide on Human Airway Anion Secretion

http://hdl.handle.net/2237/18885
7d04943f-f76d-490a-8427-274cc485e2d5
名前 / ファイル ライセンス アクション
k10052.pdf k10052.pdf (759.5 kB)
Item type 学位論文 / Thesis or Dissertation(1)
公開日 2013-11-14
タイトル
タイトル Nongenomic Effects of Fluticasone Propionate and Budesonide on Human Airway Anion Secretion
著者 Mizutani, Takefumi

× Mizutani, Takefumi

WEKO 50162

Mizutani, Takefumi

Search repository
Morise, Masahiro

× Morise, Masahiro

WEKO 50163

Morise, Masahiro

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Ito, Yasushi

× Ito, Yasushi

WEKO 50164

Ito, Yasushi

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Hibino, Yoshitaka

× Hibino, Yoshitaka

WEKO 50165

Hibino, Yoshitaka

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Matsuno, Tadakatsu

× Matsuno, Tadakatsu

WEKO 50166

Matsuno, Tadakatsu

Search repository
Ito, Satoru

× Ito, Satoru

WEKO 50167

Ito, Satoru

Search repository
Hashimoto, Naozumi

× Hashimoto, Naozumi

WEKO 50168

Hashimoto, Naozumi

Search repository
Sato, Mitsuo

× Sato, Mitsuo

WEKO 50169

Sato, Mitsuo

Search repository
Kondo, Masashi

× Kondo, Masashi

WEKO 50170

Kondo, Masashi

Search repository
Imaizumi, Kazuyoshi

× Imaizumi, Kazuyoshi

WEKO 50171

Imaizumi, Kazuyoshi

Search repository
Hasegawa, Yoshinori

× Hasegawa, Yoshinori

WEKO 50172

Hasegawa, Yoshinori

Search repository
キーワード
主題Scheme Other
主題 fluticasone propionate
キーワード
主題Scheme Other
主題 budesonide
キーワード
主題Scheme Other
主題 cAMP
キーワード
主題Scheme Other
主題 anion transporter
キーワード
主題Scheme Other
主題 forskolin
抄録
内容記述 This study investigated the physiological effects of inhaled corticosteroids, which are used widely to treat asthma. The application of fluticasone propionate (FP, 100 μM) induced sustained increases in the short-circuit current (ISC) in human airway Calu-3 epithelial cells. The FP-induced ISC was prevented by the presence of H89 (10 μM, a protein kinase A inhibitor) and SQ22536 (100 μM, an adenylate cyclase inhibitor). The FP-induced responses involved bumetanide (a Na^+–K^+–2Cl^− cotransporter inhibitor)–sensitive and 4,4′-dinitrostilbene-2,2′-disulfonic acid (an inhibitor of HCO3^−-dependent anion transporters)–sensitive components, both of which reflect basolateral anion transport. Further, FP augmented apical membrane Cl− current (ICl), reflecting cystic fibrosis transmembrane conductance regulator (CFTR)–mediated conductance, in the nystatin-permeabilized monolayer. In ISC and ICl responses, FP failed to enhance the responses to forskolin (10 μM, an adenylate cyclase activator). Nevertheless, we found that FP synergistically increased cytosolic cAMP concentrations in combination with forskolin. All these effects of FP were reproduced with the use of budesonide. Collectively, inhaled corticosteroids such as FP and budesonide stimulate CFTR-mediated anion transport through adenylate cyclase–mediated mechanisms in a nongenomic fashion, thus sharing elements of a common pathway with forskolin. However, the corticosteroids cooperate with forskolin for synergistic cAMP production, suggesting that the corticosteroids and forskolin do not compete with each other to exert their effects on adenylate cyclase. Considering that such synergism was also observed in the FP/salmeterol combination, these nongenomic aspects may play therapeutic roles in mucus congestive airway diseases, in addition to genomic aspects that are generally recognized.
内容記述タイプ Abstract
内容記述
内容記述 名古屋大学博士学位論文 学位の種類 : 博士(医学)(課程) 学位授与年月日:平成25年3月25日 水谷武史氏の博士論文として提出された
内容記述タイプ Other
出版者
出版者 American thoracic society
言語
言語 eng
資源タイプ
資源 http://purl.org/coar/resource_type/c_46ec
タイプ thesis
ISSN
収録物識別子タイプ ISSN
収録物識別子 1044-1549
書誌情報 American Journal of Respiratory Cell and Molecular Biology

巻 47, 号 5, p. 645-651, 発行日 2012-11
学位名
学位名 博士(医学)
学位授与機関
学位授与機関名
学位授与機関名 名古屋大学
学位授与年度
学位授与年度 2012
学位授与年月日
学位授与年月日 2012-11-01
学位授与番号
学位授与番号 13901甲第10052号
著者版フラグ
値 publisher
URI
識別子 http://dx.doi.org/10.1165/rcmb.2012-0076OC
識別子タイプ DOI
URI
識別子 http://hdl.handle.net/2237/18885
識別子タイプ HDL
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