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A low [Ca2+]i-induced enhancement of cAMP-activated ciliary beating by PDE1A inhibition in mouse airway cilia

  • Signaling and cell physiology
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Abstract

This study demonstrated that PDE1 (phosphodiesterase 1) existing in the ciliary beat frequency (CBF)-regulating metabolon regulates CBF in procaterol-stimulated lung airway ciliary cells of mouse. Procaterol (an β2-agonist) increased the ciliary bend angle (CBA) and CBF via cAMP accumulation in the ciliary cells of mice: interestingly, the time course of CBF increase was slower than that of CBA increase. However, IBMX (3-isobutyl-1-methylxanthine, an inhibitor of PDE) increased CBA and CBF in an identical time course. Lowering an intracellular Ca2+ concentration ([Ca2+]i) caused by switching to an EGTA-containing Ca2+-free solution from normal one elevated the procaterol-induced increasing rate of CBF. These observations suggest that Ca2+-dependent PDE1 controls cAMP-stimulated CBF increase. Either application of 8MmIBMX (8-methoxymethyl-IBMX, a selective PDE1 inhibitor), BAPTA-AM (an intracellular Ca2+ chelator), or calmidazolium (an inhibitior of calmodulin) alone increased CBA and CBF in the lung airway ciliary cells and increased cAMP contents in the isolated lung cells, and like IBMX, each application of the compound made the time courses of CBA and CBF increase stimulated by procaterol identical. The immunoelectron microscopic examinations revealed that PDE1A exists in the space between the nine doublet tubules ring and plasma membrane in the lung airway cilium, where the outer dynein arm (a molecular motor regulating CBF) functions. In conclusion, PDE1A is a key factor slowing the time course of the procaterol-induced increase in CBF via degradation of cAMP in the CBF-regulating metabolon of the mouse lung airway cilia.

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Acknowledgements

We thank the Osaka Medical College for giving us an opportunity to perform the experiments using the video microscope equipped with a high-speed camera. This work is partly supported by the contracted research fund from Otsuka Pharmaceutical Co., Ltd. (Tokyo, Japan).

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Authors and Affiliations

  1. Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Haruka Kogiso, Shigekuni Hosogi, Yukiko Ikeuchi, Toshio Inui, Yoshinori Marunaka & Takashi Nakahari

  2. Bio-Ionomics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Shigekuni Hosogi, Toshio Inui, Yoshinori Marunaka & Takashi Nakahari

  3. Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences, Takatsuki, Japan

    Saori Tanaka, Chikao Shimamoto & Hitoshi Matsumura

  4. Department of Microbiology and Infection Control, Osaka Medical College, Takatsuki, Japan

    Takashi Nakano & Koh-ichi Sano

  5. Saisei Mirai Clinics, Moriguchi, Japan

    Toshio Inui

  6. Japan Institute for Food Education and Health, St Agnes’ University, Kyoto, Japan

    Yoshinori Marunaka & Takashi Nakahari

Authors
  1. Haruka Kogiso
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  2. Shigekuni Hosogi
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  3. Yukiko Ikeuchi
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  4. Saori Tanaka
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  5. Chikao Shimamoto
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  6. Hitoshi Matsumura
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  7. Takashi Nakano
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  8. Koh-ichi Sano
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  9. Toshio Inui
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  10. Yoshinori Marunaka
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  11. Takashi Nakahari
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Corresponding author

Correspondence to Takashi Nakahari.

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The procedures and protocols for the experiments were approved by the Committee for Animal Research of Kyoto Prefectural University of Medicine.

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Kogiso, H., Hosogi, S., Ikeuchi, Y. et al. A low [Ca2+]i-induced enhancement of cAMP-activated ciliary beating by PDE1A inhibition in mouse airway cilia. Pflugers Arch - Eur J Physiol 469, 1215–1227 (2017). https://doi.org/10.1007/s00424-017-1988-9

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  • DOI: https://doi.org/10.1007/s00424-017-1988-9

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