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Featured researches published by Tohru Kurosawa.
Molecular Pharmaceutics | 2010
Kazuhiko Kato; Yoshiyuki Shirasaka; Erika Kuraoka; Akihiro Kikuchi; Maki Iguchi; Hisashi Suzuki; Shigeki Shibasaki; Tohru Kurosawa; Ikumi Tamai
Tebipenem pivoxil (TBPM-PI) is an oral carbapenem antibiotic for treating otolaryngologic and respiratory infections in pediatric patients. This agent is a prodrug to improve intestinal absorption of TBPM, an active form, and an absorption rate of TBPM-PI is higher than those of other prodrug-type β-lactam antibiotics. In the present study, we hypothesized that a certain mechanism other than simple diffusion is involved in the process of improved intestinal absorption of TBPM-PI and examined the mechanism. TBPM-PI uptake by Caco-2 cells was decreased by ATP-depletion and lowering the temperature to 4 °C, suggesting the contribution of carrier-mediated transport mechanisms. This uptake was partially decreased by ACE inhibitors, and the reduction of the absorption by captopril was observed by in vivo study and in situ single-pass intestinal perfusion study in rat, supporting the contribution of influx transporters. Since some ACE inhibitors and β-lactam antibiotics are reported to be substrates of PEPT and OATP families, we measured transporting activity of TBPM-PI by intestinally expressed transporters, PEPT1, OATP1A2, and OATP2B1. As a result, significant transport activities were observed by both OATP1A2 and OATP2B1 but not by PEPT1. Interestingly, pH dependence of TBPM-PI transports was different between OATP1A2 and OATP2B1, showing highest activity by OATP1A2 at pH 6.5, while OATP2B1-mediated uptake was higher at neutral and weak alkaline pH. OATP1A2 exhibited higher affinity for TBPM-PI (K(m) = 41.1 μM) than OATP2B1 (K(m) > 1 mM) for this agent. These results suggested that TBPM-PI has high intestinal apical membrane permeability due to plural intestinal transport routes, including the uptake transporters such as OATP1A2 and OATP2B1 as well as simple diffusion.
Histochemistry and Cell Biology | 2011
Kazuyuki Hiratsuka; Atsushi Momose; Norio Takagi; Hiroyuki Sasaki; Shan-Ai Yin; Mariko Fujita; Takayuki Ohtomo; Kouichi Tanonaka; Hiroo Toyoda; Hisashi Suzuki; Tohru Kurosawa; Junji Yamada
Organic solute carrier partner 1 (OSCP1) is a mammalian, transporter-related protein that is able to facilitate the uptake of structurally diverse organic compounds into the cell when expressed in Xenopus laevis oocytes. This protein has been implicated in testicular handling of organic solutes because its mRNA expression is almost exclusive in the testis. However, in this study, we demonstrated significant expression of OSCP1 protein in mouse brain, the level of which was rather higher than that in the testis, although the corresponding mRNA expression was one-tenth of the testicular level. Immunohistochemistry revealed that OSCP1 was broadly distributed throughout the brain, and various neuronal cells were immunostained, including pyramidal cells in the cerebral cortex and hippocampus. However, there was no evidence of OSCP1 expression in glia. In primary cultures of cerebral cortical neurons, double-labeling immunofluorescence localized OSCP1 to the cytosol throughout the cell body and neurites including peri-synaptic regions. This was consistent with the subcellular fractionation of brain homogenates, in which OSCP1 was mainly recovered after centrifugation both in the cytosolic fraction and the particulate fraction containing synaptosomes. Immunoelectron microscopy of brain sections also demonstrated OSCP1 in the cytosol near synapses. In addition, it was revealed that changes in the expression level of OSCP1 correlated with neuronal maturation during postnatal development of mouse brain. These results indicate that OSCP1 may have a role in the brain indirectly mediating substrate uptake into the neurons in adult animals.
Biological & Pharmaceutical Bulletin | 2009
Masahiro Nomoto; Masaaki Miyata; Shan-Ai Yin; Yasushi Kurata; Miki Shimada; Kouichi Yoshinari; Frank J. Gonzalez; Kokichi Suzuki; Shigeki Shibasaki; Tohru Kurosawa; Yasushi Yamazoe
Biological & Pharmaceutical Bulletin | 2008
Makoto Aoki; Maki Iguchi; Hiroyuki Hayashi; Hisashi Suzuki; Shigeki Shibasaki; Tohru Kurosawa; Masahiro Hayashi
European Journal of Pharmacology | 2007
Masahiro Nomoto; Masaaki Miyata; Miki Shimada; Kouichi Yoshinari; Frank J. Gonzalez; Shigeki Shibasaki; Tohru Kurosawa; Yasuhiro Shindo; Yasushi Yamazoe
The Journal of Antibiotics | 2009
Kijima K; Morita J; Suzuki K; Aoki M; Kato K; Hiroyuki Hayashi; Shigeki Shibasaki; Tohru Kurosawa
Drug Metabolism and Pharmacokinetics | 2007
Yukihiro Yagi; Makoto Aoki; Maki Iguchi; Shigeki Shibasaki; Tohru Kurosawa; Yukio Kato; Akira Tsuji
The Journal of Antibiotics | 2008
Nobuo Sato; Hisashi Suzuki; Hiroyuki Hayashi; Shigeki Shibasaki; Toshie Sugano; Kazunori Maebashi; Tohru Kurosawa; Mari Shiomi; Hiroyasu Ogata
The Journal of Antibiotics | 2009
Yagi Y; Nawa T; Kurata Y; Shigeki Shibasaki; Suzuki H; Tohru Kurosawa
Journal of Toxicological Sciences | 2000
Chiharu Yoshida; Sachiyo Shibutani; Syuji Ozaki; Yoshiaki Shibazaki; Hiroyasu Hayasaka; Yoko Shoji; Tohru Kurosawa; Takemi Nakayoshi