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Functional identification of organic cation transporter 1 as an atenolol transporter sensitive to flavonoids
Atenolol, a β1-adrenergic receptor blocker, is administered orally and its intestinal absorption has recently been indicated to be mediated by carrier protein and reduced markedly by ingestion of some fruit juices, such as apple and orange juices. This could be postulated to be a problem arising fro...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668658/ https://www.ncbi.nlm.nih.gov/pubmed/29124159 http://dx.doi.org/10.1016/j.bbrep.2015.06.005 |
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author | Mimura, Yoshihisa Yasujima, Tomoya Ohta, Kinya Inoue, Katsuhisa Yuasa, Hiroaki |
author_facet | Mimura, Yoshihisa Yasujima, Tomoya Ohta, Kinya Inoue, Katsuhisa Yuasa, Hiroaki |
author_sort | Mimura, Yoshihisa |
collection | PubMed |
description | Atenolol, a β1-adrenergic receptor blocker, is administered orally and its intestinal absorption has recently been indicated to be mediated by carrier protein and reduced markedly by ingestion of some fruit juices, such as apple and orange juices. This could be postulated to be a problem arising from the interaction of some components of fruit juices with atenolol at a transporter involved in its intestinal uptake, but the responsible transporter and its interacting components have not been identified yet. In an attempt to examine that possibility, we could successfully find that human organic cation transporter 1 (OCT1/SLC22A1), which is suggested to be expressed at the brush border membrane of enterocytes, is highly capable of transporting atenolol. In this attempt, OCT1 was stably expressed in Madin-Darby canine kidney II cells and the specific uptake of atenolol by the transporter was found to be saturable, conforming to the Michaelis-Menten kinetics with the maximum transport rate (V(max)) of 4.00 nmol/min/mg protein and the Michaelis constant (K(m)) of 3.08 mM. Furthermore, the OCT1-specific uptake was found to be inhibited by various flavonoids, including those contained in fruit juices that have been suggested to interfere with intestinal atenolol absorption. Particularly, phloretin and quercetin, which are major components of apple juice, were potent in inhibiting OCT1-mediated atenolol transport with the inhibition constants of 38.0 and 48.0 µM, respectively. It is also notable that the inhibition by these flavonoids was of the noncompetitive type. These results indicate that OCT1 is an atenolol transporter that may be involved in intestinal atenolol uptake and sensitive to fruit juices, although its physiological and clinical relevance remains to be further examined. |
format | Online Article Text |
id | pubmed-5668658 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-56686582017-11-09 Functional identification of organic cation transporter 1 as an atenolol transporter sensitive to flavonoids Mimura, Yoshihisa Yasujima, Tomoya Ohta, Kinya Inoue, Katsuhisa Yuasa, Hiroaki Biochem Biophys Rep Research Article Atenolol, a β1-adrenergic receptor blocker, is administered orally and its intestinal absorption has recently been indicated to be mediated by carrier protein and reduced markedly by ingestion of some fruit juices, such as apple and orange juices. This could be postulated to be a problem arising from the interaction of some components of fruit juices with atenolol at a transporter involved in its intestinal uptake, but the responsible transporter and its interacting components have not been identified yet. In an attempt to examine that possibility, we could successfully find that human organic cation transporter 1 (OCT1/SLC22A1), which is suggested to be expressed at the brush border membrane of enterocytes, is highly capable of transporting atenolol. In this attempt, OCT1 was stably expressed in Madin-Darby canine kidney II cells and the specific uptake of atenolol by the transporter was found to be saturable, conforming to the Michaelis-Menten kinetics with the maximum transport rate (V(max)) of 4.00 nmol/min/mg protein and the Michaelis constant (K(m)) of 3.08 mM. Furthermore, the OCT1-specific uptake was found to be inhibited by various flavonoids, including those contained in fruit juices that have been suggested to interfere with intestinal atenolol absorption. Particularly, phloretin and quercetin, which are major components of apple juice, were potent in inhibiting OCT1-mediated atenolol transport with the inhibition constants of 38.0 and 48.0 µM, respectively. It is also notable that the inhibition by these flavonoids was of the noncompetitive type. These results indicate that OCT1 is an atenolol transporter that may be involved in intestinal atenolol uptake and sensitive to fruit juices, although its physiological and clinical relevance remains to be further examined. Elsevier 2015-06-24 /pmc/articles/PMC5668658/ /pubmed/29124159 http://dx.doi.org/10.1016/j.bbrep.2015.06.005 Text en © 2015 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Research Article Mimura, Yoshihisa Yasujima, Tomoya Ohta, Kinya Inoue, Katsuhisa Yuasa, Hiroaki Functional identification of organic cation transporter 1 as an atenolol transporter sensitive to flavonoids |
title | Functional identification of organic cation transporter 1 as an atenolol transporter sensitive to flavonoids |
title_full | Functional identification of organic cation transporter 1 as an atenolol transporter sensitive to flavonoids |
title_fullStr | Functional identification of organic cation transporter 1 as an atenolol transporter sensitive to flavonoids |
title_full_unstemmed | Functional identification of organic cation transporter 1 as an atenolol transporter sensitive to flavonoids |
title_short | Functional identification of organic cation transporter 1 as an atenolol transporter sensitive to flavonoids |
title_sort | functional identification of organic cation transporter 1 as an atenolol transporter sensitive to flavonoids |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5668658/ https://www.ncbi.nlm.nih.gov/pubmed/29124159 http://dx.doi.org/10.1016/j.bbrep.2015.06.005 |
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