2013 Fiscal Year Final Research Report
Analysis of low temperature tolerance of membrane transporters and development of pan-transporter inhibitors
Project/Area Number |
23659081
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Medical pharmacy
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Research Institution | Hiroshima University |
Principal Investigator |
TAKANO Mikihisa 広島大学, 医歯薬保健学研究院(薬), 教授 (20211336)
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Co-Investigator(Renkei-kenkyūsha) |
YUMOTO Ryoko 広島大学, 大学院・医歯薬保健学研究院, 助教 (70379915)
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Project Period (FY) |
2011 – 2013
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Keywords | 薬物動態 / 生体膜輸送 / トランスポーター / 低温忍容性 / 汎トランスポーター阻害剤 |
Research Abstract |
Low temperature tolerance of membrane transporters, a characteristic showing transport activity even at ice-cold temperature, was examined in human erythrocytes and cultured cancer cells. A facilitative glucose transporter GLUT1 and a facilitative nucleoside transporter ENT1 showed marked low temperature tolerance in erythrocyte membrane vesicles. A secondary active monocarboxylate transporter MCT1 showed low temperature tolerance in erythrocytes. In addition, GLUT1 in culture cells such as A549 and HepG2 also showed low temperature tolerance. In order to evaluate the function of these transporters properly, I attempted to develop novel pan-transporter inhibitors (stop and washing solutions for transport study). Among various reagents tested, solutions containing urea plus formaldehyde and 2-mercaptoethanol plus glutaraldehyde were found to be effective pan-transporter inhibitors in both membrane vesicle and culture cell studies.
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