Carbocisteine stimulated an increase in ciliary bend angle via a decrease in [Cl−]i in mouse airway cilia View Full Text


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Article Info

DATE

2019-02

AUTHORS

Yukiko Ikeuchi, Haruka Kogiso, Shigekuni Hosogi, Saori Tanaka, Chikao Shimamoto, Hitoshi Matsumura, Toshio Inui, Yoshinori Marunaka, Takashi Nakahari

ABSTRACT

Carbocisteine (CCis), a mucoactive agent, is widely used to improve respiratory diseases. This study demonstrated that CCis increases ciliary bend angle (CBA) by 30% and ciliary beat frequency (CBF) by 10% in mouse airway ciliary cells. These increases were induced by an elevation in intracellular pH (pHi; the pHi pathway) and a decrease in the intracellular Cl- concentration ([Cl-]i; the Cl- pathway) stimulated by CCis. The Cl- pathway, which is independent of CO2/HCO3-, increased CBA by 20%. This pathway activated Cl- release via activation of Cl- channels, leading to a decrease in [Cl-]i, and was inhibited by Cl- channel blockers (5-nitro-2-(3-phenylpropylamino) benzoic acid and CFTR(inh)-172). Under the CO2/HCO3--free condition, the CBA increase stimulated by CCis was mimicked by the Cl--free NO3- solution. The pHi pathway, which depends on CO2/HCO3-, increased CBF and CBA by 10%. This pathway activated HCO3- entry via Na+/HCO3- cotransport (NBC), leading to a pHi elevation, and was inhibited by 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid. The effects of CCis were not affected by a protein kinase A inhibitor (1 μM PKI-A) or Ca2+-free solution. Thus, CCis decreased [Cl-]i via activation of Cl- channels including CFTR, increasing CBA by 20%, and elevated pHi via NBC activation, increasing CBF and CBA by 10%. More... »

PAGES

1-16

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s00424-018-2212-2

    DOI

    http://dx.doi.org/10.1007/s00424-018-2212-2

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1107429333

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/30291431


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