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Significance of Binding to Na,K-ATPase in the Tissue Distribution of Ouabain in Guinea Pigs

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Abstract

Ouabain binds specifically to Na,K-ATPase on the plasma membrane and therefore serves to measure the tissue concentration of Na,K-ATPase. We examined the role of ouabain binding to Na,K-ATPase in its overall tissue distribution. The tissue-to-plasma concentration ratio (K p,vivo) was defined in each tissue after intravenous administration of 3H-ouabain in guinea pigs, and specific binding of ouabain to Na,K-ATPase was measured in tissue homogenate to obtain the dissociation constant and binding capacity in each tissue. A predicted tissue-to-plasma concentration ratio (K p,vitro) was calculated using the obtained binding parameters and the volume of extracellular space in each tissue. The absolute values of K p,vitro were comparable to those of K p vivo, except in brain. Regression analysis showed that the specific binding capacity of Na,K-ATPase in each tissue is the main factor in the tissue variation of K p,vivo. Therefore, the binding of ouabain to Na,K-ATPase plays a significant role in the tissue distribution of ouabain.

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Author notes

  1. Hideyoshi Harashima

    Present address: Faculty of Pharmaceutical Sciences, University of Tokushima, 1-78-1, Shomachi, Tokushima, 770, Japan

  2. Michio Mamiya

    Present address: Shionogi Research Laboratories, Shionogi and Co., Ltd., 2-1-3, Kuise-Terashima, Amagasaki City, Hyogo, 660, Japan

  3. Yasufumi Sawada & Tatsuji Iga

    Present address: Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, University of Tokyo, Kongo, Bunkyo-ku, Tokyo, 113, Japan

  4. Manabu Hanano

    Present address: College of Pharmacy, Nihon University, 7-7-1, Narawashinodai, Funabashi City, 274, Japan

Authors and Affiliations

  1. Faculty of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo, 113, Japan

    Hideyoshi Harashima, Michio Mamiya, Masayo Yamazaki, Yuichi Sugiyama, Yasufumi Sawada, Tatsuji Iga & Manabu Hanano

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  1. Hideyoshi Harashima
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Harashima, H., Mamiya, M., Yamazaki, M. et al. Significance of Binding to Na,K-ATPase in the Tissue Distribution of Ouabain in Guinea Pigs. Pharm Res 9, 474–479 (1992). https://doi.org/10.1023/A:1015832127969

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