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Sodium Nitroprusside Enhances Absorption in the Rat Jejunum via the Transcellular Route

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Abstract

It was reported that nitric oxide (NO) donors increased the permeability of water-soluble compounds across intestinal membrane with neither loss of cell viability nor release of lactate dehydrogenase. Therefore, the detail mechanism of action of NO donors on the gastrointestinal membrane has yet to be clarified. We previously reported the possibility of the enhancing effect of the NO donor on the membrane permeability via transcellular route. The purpose of this study is to clarify the mechanism of the membrane permeation-enhancing effect via the transcellular route by sodium nitroprusside (SNP), which is one of the NO donors. The effect of SNP on membrane permeation was examined by the in vitro sac method using rat jejunum. SNP increased the membrane permeation of rhodamine 123 same as using N-acetyl-l-cysteine and dithiothreitol which removes unstirred water layer (UWL). Moreover, SNP increased the membrane permeation of antipyrine and β-naphthol, which are transcellular markers. And it was also investigated the expression levels of mucins (MUCs) which are construction component of UWL and the slight change of MUCs expression by SNP was shown. It was suggested that the expression balance of MUCs is necessary to regulate transcellular permeation, and SNP may affect to UWL. This finding was considered useful for highly lipophilic drugs for which membrane permeation is restricted by the UWL.

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Acknowledgements

The authors thank Miss Minami Nakagawa, Mr. Yuki Aizawa, Mr. Takahito Furuya, Miss Nozomi Goto, Miss Minori Sadaoka and Mr. Yuya Komazaki for technical assistance.

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Authors and Affiliations

  1. Division of Clinical Pharmaceutics, Department of Pharmaceutical Sciences, Nihon Pharmaceutical University, 10281, Komuro, Ina-machi, Kitaadachi-gun, Saitama, 362-0806, Japan

    Yusuke Takizawa

  2. Department of Drug Absorption and Pharmacokinetics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, 1432-1 Horinouchi, Hachioji, Tokyo, 192-0392, Japan

    Yusuke Takizawa, Yoshifusa Tobe, Nasa Sakamoto & Junya Sakamoto

  3. Laboratory of Molecular Pharmaceutics and Technology, Faculty of Pharmacy, Takasaki University of Health and Welfare, 60 Nakaorui-machi, Takasaki, Gunma, 370-0033, Japan

    Masahiro Hayashi

Authors
  1. Yusuke Takizawa
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  2. Yoshifusa Tobe
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  3. Nasa Sakamoto
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  4. Junya Sakamoto
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  5. Masahiro Hayashi
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by YT, NS, and JS. The first draft of the manuscript was written by YT and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yusuke Takizawa.

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Takizawa, Y., Tobe, Y., Sakamoto, N. et al. Sodium Nitroprusside Enhances Absorption in the Rat Jejunum via the Transcellular Route. J Membrane Biol 253, 221–228 (2020). https://doi.org/10.1007/s00232-020-00118-1

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  • DOI: https://doi.org/10.1007/s00232-020-00118-1

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