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Int. J. Mol. Sci. 2018, 19(3), 658; https://doi.org/10.3390/ijms19030658

Seihai-to (TJ-90)-Induced Activation of Airway Ciliary Beatings of Mice: Ca2+ Modulation of cAMP-Stimulated Ciliary Beatings via PDE1

1
Department of Molecular Cell Physiology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
2
Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences, Takatsuki 569-1096 Japan
3
Saisei Mirai Clinics, Moriguchi 570-0012, Japan
4
Department of Bio-Ionomics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
5
Japan Institute for Food Education and Health, St. Agnes’ University, Kyoto 602-8013, Japan
*
Author to whom correspondence should be addressed.
Received: 26 December 2017 / Revised: 20 February 2018 / Accepted: 23 February 2018 / Published: 26 February 2018
(This article belongs to the Special Issue Ion Transporters and Channels in Physiology and Pathophysiology)
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Abstract

Sei-hai-to (TJ-90, Qing Fei Tang), a Chinese traditional medicine, increases ciliary beat frequency (CBF) and ciliary bend angle (CBA) mediated via cAMP (3′,5′-cyclic adenosine monophosphate) accumulation modulated by Ca2+-activated phosphodiesterase 1 (PDE1A). A high concentration of TJ-90 (≥40 μg/mL) induced two types of CBF increases, a transient increase (an initial increase, followed by a decrease) and a sustained increase without any decline, while it only sustained the CBA increase. Upon inhibiting increases in intracellular Ca2+ concentration ([Ca2+]i) by 10 μM BAPTA-AM (Ca2+-chelator, 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester) or Ca2+/calmodulin-dependent PDE1 by 8MmIBMX (a selective PDE1 inhibitor), TJ-90 (400 μg/mL) induced only the sustained CBF increase without any transient CBF increase. The two types of the CBF increase (the transient increase and the sustained increase) induced by TJ-90 (≥40 μg/mL) were mimicked by the stimulation with both procaterol (100 pM) and ionomycin (500 nM). Thus, TJ-90 stimulates small increases in the intracellular cAMP concentration ([cAMP]i) and [Ca2+]i in airway ciliary cells of mice. These small increases in [cAMP]i and [Ca2+]i cause inducing a transient CBF increase or a sustained CBF increase in an airway ciliary cells, depending on the dominant signal, Ca2+-signal, or cAMP-signal. View Full-Text
Keywords: airway; cilia; PDE1; dynein; cAMP; Ca2+ airway; cilia; PDE1; dynein; cAMP; Ca2+
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Kogiso, H.; Ikeuchi, Y.; Sumiya, M.; Hosogi, S.; Tanaka, S.; Shimamoto, C.; Inui, T.; Marunaka, Y.; Nakahari, T. Seihai-to (TJ-90)-Induced Activation of Airway Ciliary Beatings of Mice: Ca2+ Modulation of cAMP-Stimulated Ciliary Beatings via PDE1. Int. J. Mol. Sci. 2018, 19, 658.

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