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Kinetic study of anti-viral ribavirin uptake mediated by hCNT3 and hENT1 in Xenopus laevis oocytes

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Title: Kinetic study of anti-viral ribavirin uptake mediated by hCNT3 and hENT1 in Xenopus laevis oocytes
Authors: Yamamoto, Takashi Browse this author
Sugawara, Mitsuru Browse this author →KAKEN DB
Kikukawa, Takashi Browse this author
Miyauchi, Seiji Browse this author
Yamaguchi, Masahiro Browse this author
Tero, Atsushi Browse this author
Takagi, Seiji Browse this author
Nakagaki, Toshiyuki Browse this author
Keywords: Diffusion
Mathematical model
Nucleoside transporter
Issue Date: Mar-2010
Publisher: Elsevier
Journal Title: Biophysical Chemistry
Volume: 147
Issue: 1-2
Start Page: 59
End Page: 65
Publisher DOI: 10.1016/j.bpc.2009.12.012
PMID: 20096989
Abstract: Transport across the cell membrane is crucial in drug delivery. However, the process is complicated because nucleoside derivatives that are commonly used as anti-viral drugs are transported through two different types of specific transporters: concentrative transporters and equilibrative transporters. Cross-disciplinary approaches involving both biological experiments and theoretical considerations are therefore necessary to study the transport of nucleoside analogues such as ribavirin. Here we constructed an experimental model system using the Xenopus laevis oocyte that expressed examples of both types of transporters: human concentrative nucleoside transporter 3 and human equilibrative transporter 1. We also performed a kinetic study. Experimental results showed that the transport of ribavirin could be reduced by inhibiting one of the two types of transporters, which seems to be counterintuitive. We therefore designed a simple mathematical model of the dynamics of ribavirin uptake and analyzed the model behaviors using a numerical simulation. The theoretical results reproduced the experimentally observed phenomena and suggested a possible mechanism for the process. Based on this mechanism, we predicted some potential methods for the effective uptake of ribavirin from a dynamics point of view.
Type: article (author version)
Appears in Collections:電子科学研究所 (Research Institute for Electronic Science) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 中垣 俊之

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