Noncompetitive Inhibition of Proton-coupled Folate Transporter by Myricetin
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- FURUMIYA Mai
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University Department of Biopharmaceutics, College of Pharmacy, Kinjo Gakuin University
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- INOUE Katsuhisa
- Department of Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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- NISHIJIMA Chihiro
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University
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- YAMASHIRO Takahiro
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University
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- INAOKA Erina
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University
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- OHTA Kinya
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University
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- HAYASHI Yayoi
- Department of Biopharmaceutics, College of Pharmacy, Kinjo Gakuin University
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- YUASA Hiroaki
- Department of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Nagoya City University
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抄録
Myricetin is a flavonoid that has recently been suggested to interfere with the intestinal folate transport system. The present study was conducted to examine that possibility, focusing on its inhibitory effect on proton-coupled folate transporter (PCFT) as the molecular entity of the transport system. The uptake transport of folate was first examined in the Caco-2 cell as an intestinal epithelial cell model, and its carrier-mediated component, of which the Michaelis constant (Km) was 0.407 µM, was found to be noncompetitively inhibited by myricetin with an inhibition constant (Ki) of 61 µM. Consistent with that, folate transport by human PCFT stably expressed in Madin-Darby canine kidney II (MDCKII) cells, of which the Km was 1.246 µM, was also noncompetitively inhibited by myricetin with a Ki of 130 µM. Thus, myricetin was suggested to inhibit intestinal folate transport by acting noncompetitively on PCFT, although the Km and Ki were similarly shifted to some extent to be smaller in Caco-2 cells. Finally, epigallocatechin-3-gallate was also suggested to act in a noncompetitive manner as an inhibitory flavonoid. Care may need to be taken, therefore, in the ingestion of myricetin and some flavonoids to maintain the absorption of folate and antifolate drugs.
収録刊行物
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- Ｄｒｕｇ Ｍｅｔａｂｏｌｉｓｍ ａｎｄ Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ
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Ｄｒｕｇ Ｍｅｔａｂｏｌｉｓｍ ａｎｄ Ｐｈａｒｍａｃｏｋｉｎｅｔｉｃｓ 29 (4), 312-316, 2014
日本薬物動態学会