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Research ArticleEndocrine and Diabetes

Adiponectin Enhances Calcium Dependency of Mouse Bladder Contraction Mediated by Protein Kinase Cα Expression

Koji Nobe, Akiko Fujii, Kiyomi Saito, Takaharu Negoro, Yoshio Ogawa, Yasuko Nakano, Terumasa Hashimoto and Kazuo Honda
Journal of Pharmacology and Experimental Therapeutics April 2013, 345 (1) 62-68; DOI: https://doi.org/10.1124/jpet.112.202028
Koji Nobe
Departments of Pharmacology (K.N., A.F., T.H., K.H.), Clinical and Molecular Pharmacokinetics/Pharmacodynamics (K.S.), and Pharmacogenomics (T.N., Y.N.), School of Pharmacy, Showa University, Tokyo, Japan; and Department of Urology, Showa University Hospital, Shinagawa-ku, Tokyo, Japan (Y.O.)
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Akiko Fujii
Departments of Pharmacology (K.N., A.F., T.H., K.H.), Clinical and Molecular Pharmacokinetics/Pharmacodynamics (K.S.), and Pharmacogenomics (T.N., Y.N.), School of Pharmacy, Showa University, Tokyo, Japan; and Department of Urology, Showa University Hospital, Shinagawa-ku, Tokyo, Japan (Y.O.)
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Kiyomi Saito
Departments of Pharmacology (K.N., A.F., T.H., K.H.), Clinical and Molecular Pharmacokinetics/Pharmacodynamics (K.S.), and Pharmacogenomics (T.N., Y.N.), School of Pharmacy, Showa University, Tokyo, Japan; and Department of Urology, Showa University Hospital, Shinagawa-ku, Tokyo, Japan (Y.O.)
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Takaharu Negoro
Departments of Pharmacology (K.N., A.F., T.H., K.H.), Clinical and Molecular Pharmacokinetics/Pharmacodynamics (K.S.), and Pharmacogenomics (T.N., Y.N.), School of Pharmacy, Showa University, Tokyo, Japan; and Department of Urology, Showa University Hospital, Shinagawa-ku, Tokyo, Japan (Y.O.)
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Yoshio Ogawa
Departments of Pharmacology (K.N., A.F., T.H., K.H.), Clinical and Molecular Pharmacokinetics/Pharmacodynamics (K.S.), and Pharmacogenomics (T.N., Y.N.), School of Pharmacy, Showa University, Tokyo, Japan; and Department of Urology, Showa University Hospital, Shinagawa-ku, Tokyo, Japan (Y.O.)
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Yasuko Nakano
Departments of Pharmacology (K.N., A.F., T.H., K.H.), Clinical and Molecular Pharmacokinetics/Pharmacodynamics (K.S.), and Pharmacogenomics (T.N., Y.N.), School of Pharmacy, Showa University, Tokyo, Japan; and Department of Urology, Showa University Hospital, Shinagawa-ku, Tokyo, Japan (Y.O.)
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Terumasa Hashimoto
Departments of Pharmacology (K.N., A.F., T.H., K.H.), Clinical and Molecular Pharmacokinetics/Pharmacodynamics (K.S.), and Pharmacogenomics (T.N., Y.N.), School of Pharmacy, Showa University, Tokyo, Japan; and Department of Urology, Showa University Hospital, Shinagawa-ku, Tokyo, Japan (Y.O.)
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Kazuo Honda
Departments of Pharmacology (K.N., A.F., T.H., K.H.), Clinical and Molecular Pharmacokinetics/Pharmacodynamics (K.S.), and Pharmacogenomics (T.N., Y.N.), School of Pharmacy, Showa University, Tokyo, Japan; and Department of Urology, Showa University Hospital, Shinagawa-ku, Tokyo, Japan (Y.O.)
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Abstract

Adiponectin is an adipose tissue–secreted protein and is a multifunctional adipocytokine. However, the association of adiponectin with bladder contraction has not been investigated. In this study, the adiponectin-sense transgenic mouse (Adip-Sen mouse; age, 16–24 weeks; male) and age-matched controls (C57Bl mouse) were studied. The Adip-Sen mouse showed a significant increase in plasma adiponectin levels (56.2%; P < 0.01), compared with those in the C57Bl mouse, without affecting other lipid parameters. Isometric force development in bladder smooth muscle tissues were detected using an organ-bath system. Although carbachol (CCh)–induced (0.1–100 µM) time- and dose-dependent contractions in Adip-Sen mouse bladder were slightly enhanced, compared with those in the C57Bl mouse during a low range (0.3–1.0 µM) of CCh, differences could not be detected with other CCh concentrations. However, the reduction in contraction under Ca2+-replaced conditions was significantly different between Adip-Sen and C57Bl mice (94.1 and 66.3% of normal contraction, respectively; n = 5). A parameter of Ca2+ sensitivity, the relation between intracellular Ca2+ concentration and contraction, was increased in the Adip-Sen mouse, compared with that in the C57B1 mouse. This Ca2+ dependency in the Adip-Sen mouse was reduced by a protein kinase C (PKC) inhibitor, but not by a Rho kinase inhibitor. Expression of the calcium-dependent isoform of PKC, PKCα, was increased in the Adip-Sen mouse bladder, and CCh-induced phosphorylation of PKCα was also enhanced, compared with those in the C57Bl mouse. In conclusion, adiponectin is associated with bladder smooth muscle contraction, which involves an increase in Ca2+ dependency of contraction mediated by PKCα expression.

Footnotes

    • Received November 19, 2012.
    • Accepted January 29, 2013.
  • This study was supported by a Grant-in-Aid for Encouragement of Young Scientists from the Ministry of Education, Culture, Sports, Science and Technology (MEXT; 21590290) in Japan; and a Private University High Technology Research Center Project matching fund subsidy from MEXT (NEXT; S1001011).

  • dx.doi.org/10.1124/jpet.112.202028.

  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 345 (1)
Journal of Pharmacology and Experimental Therapeutics
Vol. 345, Issue 1
1 Apr 2013
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Research ArticleEndocrine and Diabetes

Association of Adiponectin with Bladder Contraction

Koji Nobe, Akiko Fujii, Kiyomi Saito, Takaharu Negoro, Yoshio Ogawa, Yasuko Nakano, Terumasa Hashimoto and Kazuo Honda
Journal of Pharmacology and Experimental Therapeutics April 1, 2013, 345 (1) 62-68; DOI: https://doi.org/10.1124/jpet.112.202028

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Research ArticleEndocrine and Diabetes

Association of Adiponectin with Bladder Contraction

Koji Nobe, Akiko Fujii, Kiyomi Saito, Takaharu Negoro, Yoshio Ogawa, Yasuko Nakano, Terumasa Hashimoto and Kazuo Honda
Journal of Pharmacology and Experimental Therapeutics April 1, 2013, 345 (1) 62-68; DOI: https://doi.org/10.1124/jpet.112.202028
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