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First published on August 4, 2005; DOI: 10.1124/jpet.105.086827

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Received for publication March 24, 2005.
Revised August 1, 2005.
Accepted for publication August 2, 2005.

Functional analysis of organic cation transporter 3 (OCT3) expressed in human placenta

Ryoko Sata 1, Hisakazu Ohtani 1, Masayuki Tsujimoto 1, Hideyasu Murakami 1, Noriko Koyabu 1, Takanori Nakamura 1, Takeshi Uchiumi 1, Michihiko Kuwano 1, Hideaki Nagata 1, Kiyomi Tsukimori 1, Hitoo Nakano 1, Yasufumi Sawada 1*

1 Kyushu University

* Address correspondence to: E-mail: sawada{at}mol.f.u-tokyo.ac.jp

Abstract

The aim of this study is to investigate the placental transport mechanism of cationic compounds by comparison of the uptake of an organic cation into human placental basal membrane vesicles (BLMVs) with that into organic cation transporter 3 (OCT3)-expressing cells. RT-PCR analysis demonstrated that OCT3 is the only OCT isoform expressed in the human placenta. The function of OCT3 was investigated by measuring the uptake of 1-methyl-4-phenylpyridinium (MPP+) into HEK293 cells stably expressing OCT3 (HEK/OCT3 cells). The OCT3-mediated uptake of MPP+ was sodium- and chloride-independent and saturable, with a Michaelis constant (Km) of 70 µM. The OCT3-mediated uptake was inhibited by various cationic drugs in a concentration-dependent manner, but not by anionic compounds, such as p-aminohippuric acid and captopril, or a zwitter ion, carnitine. Western blotting analysis of membrane vesicles prepared from human term placenta revealed that OCT3 is expressed only in BLMVs, but not in microvillous membrane vesicles (BBMVs). The uptake of MPP+ into BLMVs was membrane potential-dependent and saturable, with a Km value of 39 µM, which is similar to that in HEK293/OCT3 cells. The inhibitory spectrum of various compounds on MPP+ uptake by BLMVs was also similar to that in HEK293/OCT3 cells. These results suggest that OCT3 is expressed on the basal membrane of human trophoblast cells and plays an important role in the placental transport of cationic compounds.


Key words: blood-placental barrier, fetus, membrane vesicles, organic cation transporter, placenta, trophoblast cells


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