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

2012 Fiscal Year Final Research Report

• Project/Area Number: 22590508
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Hyogo 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
• Keywords: 薬物代謝酵素 / トランスポーター

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.