Aromatase knockout mice reveal an impact of estrogen on drug-induced alternation of murine electrocardiography parameters
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- Kurokawa Junko
- Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical Dental University
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- Sasano Tetsuo
- Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical Dental University
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- Kodama Masami
- Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical Dental University
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- Li Min
- Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical Dental University
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- Ebana Yusuke
- Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical Dental University
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- Harada Nobuhiro
- Department of Biochemistry, School of Medicine, Fujita Health University
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- Honda Shin-ichiro
- Department of Biochemistry, School of Medicine, Fujita Health University
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- Nakaya Haruaki
- Department of Pharmacology, Chiba University Graduate School of Medicine
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- Furukawa Tetsushi
- Department of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical Dental University
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Our in vitro characterization showed that physiological concentrations of estrogen partially suppressed the IKr channel current in guinea pig ventricular myocytes and the human ether-a-go-go-related gene (hERG) channel currents in CHO-K1 cells regardless of estrogen receptor signaling and revealed that the partially suppressed hERG currents enhanced the sensitivity to the hERG blocker E-4031. To obtain in vivo proof-of-concept data to support the effects of estrogen on cardiac electrophysiology, we here employed an aromatase knockout mouse as an in vivo estrogen-null model and compared the acute effects of E-4031 on cardiac electrophysiological parameters with those in wild-type mice (C57/BL6J) by recording surface electrocardiogram (ECG). The ablation of circulating estrogens blunted the effects of E-4031 on heart rate and QT interval in mice under a denervation condition. Our result provides in vivo proof of principle and demonstrates that endogenous estrogens increase the sensitivity of E-4031 to cardiac electrophysiology.
収録刊行物
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- Ｔｈｅ Ｊｏｕｒｎａｌ ｏｆ Ｔｏｘｉｃｏｌｏｇｉｃａｌ Ｓｃｉｅｎｃｅｓ
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Ｔｈｅ Ｊｏｕｒｎａｌ ｏｆ Ｔｏｘｉｃｏｌｏｇｉｃａｌ Ｓｃｉｅｎｃｅｓ 40 (3), 339-348, 2015
一般社団法人 日本毒性学会
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詳細情報 詳細情報について
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- CRID
- 1390282679881870208
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- NII論文ID
- 130005068413
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- NII書誌ID
- AN00002808
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- ISSN
- 18803989
- 03881350
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- NDL書誌ID
- 026522732
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- PubMed
- 25972195
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
- KAKEN
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- 抄録ライセンスフラグ
- 使用不可