Involvement of Human Multidrug and Toxic Compound Extrusion (MATE) Transporters in Testosterone Transport
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- Goda Mitsuhiro
- Department of Pharmacy, Tokushima University Hospital Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences
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- Ikehara Momo
- Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
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- Sakitani Mako
- Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
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- Oda Kana
- Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
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- Ishizawa Keisuke
- Department of Pharmacy, Tokushima University Hospital Department of Clinical Pharmacology and Therapeutics, Tokushima University Graduate School of Biomedical Sciences
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- Otsuka Masato
- Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Setsunan University
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<p>Multidrug and toxic compound extrusion (MATE) transporters are primarily expressed in the kidneys and liver, where they contribute to the excretion of organic cations. Our previous study suggested that pig MATE2 (class III) participates in testosterone secretion from Leydig cells. In humans, it is unclear which MATE class is involved in testosterone transport. In this study, we aimed to clarify whether human MATE1 (hMATE1) or human MATE2K (hMATE2K) mediates testosterone transport. To confirm that testosterone inhibits transporter-mediated tetraethylammonium (TEA) uptake, a cis-inhibition assay was performed using cells that stably expressed hMATE1 or hMATE2K. Docking simulations were performed to characterize differences in the binding of hMATE1 and hMATE2K to testosterone. Transport experiments in LLC-PK1 cells that stably expressed hMATE1 were used to test whether hMATE1 mediates testosterone transport. We detected differences between the amino acid sequences of the substrate-binding sites of hMATE1 and hMATE2K that could potentially be involved in testosterone binding. Testosterone and estradiol inhibited TEA uptake mediated by hMATE1 but not that mediated by hMATE2K. Transport experiments in LLC-PK1 cells indicated that testosterone might be transported via hMATE1. This study suggested that hMATE1, but not hMATE2K, is involved in human testosterone transport.</p>
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 44 (4), 501-506, 2021-04-01
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390006065654222848
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- NII論文ID
- 130008014288
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- NII書誌ID
- AA10885497
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 031366551
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- PubMed
- 33790101
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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
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