Functional Identification of Plasma Membrane Monoamine Transporter (PMAT/SLC29A4) as an Atenolol Transporter Sensitive to Flavonoids Contained in Apple Juice
Functional Identification of Plasma Membrane Monoamine Transporter (PMAT/SLC29A4) as an Atenolol Transporter Sensitive to Flavonoids Contained in Apple Juice
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DOI：
10.1016/j.xphs.2017.01.009
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发表时间：
2017-09-01
影响因子：
3.8
通讯作者：
Yuasa, Hiroaki
中科院分区：
文献类型：
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作者：
Mimura, Yoshihisa;Yasujima, Tomoya;Yuasa, Hiroaki
最近有报道称，同时摄入果汁（如苹果汁）会降低阿替洛尔的肠道吸收。这一发现意味着一种可能性，一个身份不明的载体介导的运输系统，这可能会受到干扰的一些组成部分，这些果汁，可能参与阿替洛尔的吸收。为了探索这种可能性，我们成功地确定了质膜单胺转运蛋白（PMAT/SLC 29 A4）作为一种转运蛋白，可以在肠道中进行细胞阿替洛尔摄取，使用Madin-Darby犬肾II细胞稳定表达PMAT。PMAT对阿替洛尔的特异性摄取在pH 6.0左右最大，并随着pH的增加而降低。在pH 6.0时，PMAT对阿替洛尔的特异性摄取可饱和，米氏常数为0.907 mM。此外，PMAT对阿替洛尔的特异性摄取被根皮素和槲皮素广泛抑制，这是苹果汁中含有的主要黄酮类化合物，半最大抑制浓度分别为33.3和116.3 mM。PMAT特异性阿替洛尔摄取也被几种β受体阻滞剂抑制，表明它们也可能被PMAT识别和转运。这些结果表明，PMAT是一种阿替洛尔转运蛋白，可能参与肠道阿替洛尔的吸收，并对苹果汁中的黄酮类化合物敏感。(C)2017年美国药学协会（R）。爱思唯尔公司出版All rights reserved.
The intestinal absorption of atenolol has recently been reported to be reduced by simultaneous ingestion of fruit juices, such as apple juice. This finding implies a possibility that an unidentified carrier-mediated transport system, which could be interfered by some components of those juices, might be involved in atenolol absorption. In an attempt to explore that possibility, we successfully identified plasma membrane monoamine transporter (PMAT/SLC29A4) as a transporter that can operate for cellular atenolol uptake in the intestine, using Madin-Darby canine kidney II cells stably expressing PMAT. The specific uptake of atenolol by PMAT was greatest at around pH 6.0 and decreased with an increase in pH. At pH 6.0, the PMAT-specific uptake of atenolol was saturable with a Michaelis constant of 0.907 mM. Moreover, PMAT-specific atenolol uptake was extensively inhibited by phloretin and quercetin, which are the major flavonoids contained in apple juice, with the half maximal inhibitory concentrations of 33.3 and 116.3 mM, respectively. PMAT-specific atenolol uptake was also inhibited by several beta-blockers, suggesting that they may also be recognized and transported by PMAT. These results suggest that PMAT is an atenolol transporter that may be involved in intestinal atenolol absorption and sensitive to flavonoids contained in apple juice. (C) 2017 American Pharmacists Association (R). Published by Elsevier Inc. All rights reserved.