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Elucidation of drug transporting route - association between transporters and gap junction -

Research Project

Project/Area Number 22590508
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied pharmacology
Research InstitutionHyogo University of Health Sciences

Principal Investigator

MIURA Daisaku  兵庫医療大学, 薬学部, 助教 (60510873)

Co-Investigator(Kenkyū-buntansha) ANZAI Naohiko  杏林大学、獨協医科大学, 医学部, 准教授(H22)、教授(H23~) (70276054)
Co-Investigator(Renkei-kenkyūsha) KIYOMIYA Kenichi  兵庫医療大学, 薬学部, 教授 (50234399)
Project Period (FY) 2010 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000)
Fiscal Year 2010: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords薬物代謝酵素 / トランスポーター / ギャップ結合 / タンパク質相互作用 / 細胞・組織 / 薬物輸送 / 蛋白質相互作用 / コネキシン / 腎尿細管 / HK-2細胞
Research Abstract

Transport systems across the biological membrane are considered as basal mechanism for homeostasis. In this study, our aim is to elucidate transport mechanism of materials in the tissue focusing drug transporters and gap junctions. RT-PCR analysis revealed mRNA of connexin (Cx) 26, 43, 45 and 59 were expressed in the HEK293 cell line. We established stable HEK293 cell line expressing SLC22A6 (OAT1), A8 (OAT3), A11 (OAT4) and A12 (URAT1). Immuno-co-precipitation analysis showed no protein-protein interaction between Cxs and SLC22 family transporters examined in this study. In bilayer transport assay, accumulation of 14C-labelled uric acid (UA) was increased by HEK-URAT1 cell line (upper layer), but accumulation of 14C-labelled p-aminohippurate (PAH) was not increased by HEK-OAT1 cell line (upper layer). This study suggests that there seemed no protein-protein interaction between Cxs and URAT1, but extracellular UA was absorbed by URAT1 and shared among adjacent cells through gap unction.

Report

(4 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Annual Research Report
  • 2010 Annual Research Report

URL: 

Published: 2010-11-30   Modified: 2019-07-29  

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