Papers - Noguchi, Saki

Organic Anion Transporter 4-Mediated Transport of Olmesartan at Basal Plasma Membrane of Human Placental Barrier

Noguchi Saki, Nishimura Tomohiro, Fujibayashi Ayasa, Maruyama Tetsuo, Tomi Masatoshi, Nakashima Emi

Journal of Pharmaceutical Sciences (WILEY-BLACKWELL)  104 ( 9 ) 3128 - 3135 2015.09

Research paper (scientific journal),  ISSN  0022-3549

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Mechanisms regulating fetal transfer of olmesartan, an angiotensin-II receptor type 1 antagonist, are important as potential determinants of life-threatening adverse fetal effects. The purpose of this study was to examine the olmesartan transport mechanism through the basal plasma membrane (BM) of human syncytiotrophoblasts forming the placental barrier. Uptake of olmesartan by human placental BM vesicles was potently inhibited by dehydroepiandrosterone sulfate (DHEAS), estrone 3-sulfate, and bromosulfophthalein, which are all typical substrates of organic anion transporter (OAT) 4 localized at the BM of syncytiotrophoblasts, and was increased in the absence of chloride. In tetracycline-inducible OAT4-expressing cells, [H-3]olmesartan uptake was increased by tetracycline treatment. Olmesartan uptake via OAT4 was concentration dependent with a K-m of 20 M, and was increased in the absence of chloride. [H-3]Olmesartan efflux via OAT4 was also observed and was trans-stimulated by extracellular chloride and DHEAS. Thus, OAT4 mediates bidirectional transport of olmesartan and appears to regulate fetal transfer of olmesartan at the BM of syncytiotrophoblasts. Efflux transport of olmesartan via OAT4 from syncytiotrophoblasts to the fetal circulation might be facilitated in the presence of an inwardly directed physiological chloride gradient and extracellular DHEAS. (c) 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3128-3135, 2015

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Role of protein kinase A in regulating steroid sulfate uptake for estrogen production in human placental choriocarcinoma cells,

Tomi Masatoshi, Miyata Yuki, Noguchi Saki, Nishimura Sachika, Nishimura Tomohiro, Nakashima Emi

Placenta (W B SAUNDERS CO LTD)  35 ( 8 ) 658 - 660 2014.08

Research paper (scientific journal),  ISSN  0143-4004

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The purpose of this study is to assess the role of the protein kinase A (PKA) in regulating uptake of dehydroepiandrosterone sulfate (DHEAS), an estrogen precursor, by syncytiotrophoblasts. Forskolin, a PKA activator, significantly increased [H-3]DHEAS uptake and the mRNA expression levels of organic anion transporter (OAT) 4 and CYP19A1 in choriocarcinoma JEG-3 cells, while other steroid sulfate transporters present in the placenta showed no change in expression level. KT5720, a PKA inhibitor, attenuated these effects of forskolin. Accordingly, the PKA pathway appears to play an important role in estrogen synthesis by cooperatively regulating OAT4 and steroidogenic enzymes in syncytiotrophoblasts. (C) 2014 Elsevier Ltd. All rights reserved.

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