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Nongenomic Effects of Fluticasone Propionate and Budesonide on Human Airway Anion Secretion
http://hdl.handle.net/2237/18885
http://hdl.handle.net/2237/188857d04943f-f76d-490a-8427-274cc485e2d5
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
k10052.pdf (759.5 kB)
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| 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 | |||||
| 言語 | en | |||||
| 著者 |
Mizutani, Takefumi
× Mizutani, Takefumi× Morise, Masahiro× Ito, Yasushi× Hibino, Yoshitaka× Matsuno, Tadakatsu× Ito, Satoru× Hashimoto, Naozumi× Sato, Mitsuo× Kondo, Masashi× Imaizumi, Kazuyoshi× Hasegawa, Yoshinori |
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| アクセス権 | ||||||
| アクセス権 | open access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||
| 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 | ||||||
| 内容記述タイプ | Abstract | |||||
| 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. | |||||
| 言語 | en | |||||
| 内容記述 | ||||||
| 内容記述タイプ | Other | |||||
| 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 | |||||
| 言語 | ja | |||||
| 出版者 | ||||||
| 出版者 | American thoracic society | |||||
| 言語 | en | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源 | http://purl.org/coar/resource_type/c_db06 | |||||
| タイプ | doctoral thesis | |||||
| DOI | ||||||
| 関連タイプ | isVersionOf | |||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | https://doi.org/10.1165/rcmb.2012-0076OC | |||||
| ISSN | ||||||
| 収録物識別子タイプ | PISSN | |||||
| 収録物識別子 | 1044-1549 | |||||
| 書誌情報 |
en : American Journal of Respiratory Cell and Molecular Biology 巻 47, 号 5, p. 645-651, 発行日 2012-11 |
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| 学位名 | ||||||
| 言語 | ja | |||||
| 学位名 | 博士(医学) | |||||
| 学位授与機関 | ||||||
| 学位授与機関識別子Scheme | kakenhi | |||||
| 学位授与機関識別子 | 13901 | |||||
| 言語 | ja | |||||
| 学位授与機関名 | 名古屋大学 | |||||
| 言語 | en | |||||
| 学位授与機関名 | Nagoya University | |||||
| 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 | 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 | |||||
