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

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

doi:10.1007/s00424-018-2212-2

Cited by 15 publications

(59 citation statements)

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“…The reagents were prepared to their final concentrations immediately before the experiments. DMSO concentration did not exceed 0.1% …”

Section: Methodsmentioning

confidence: 99%

“…In previous studies, CCis stimulates Cl ‐ secretion by activating Cl ‐ channels in airway epithelia . Moreover, CCis increased CBF and CBA via intracellular pH (pH i ) elevation and [Cl ‐ ] i decrease in lung airway ciliary cells …”

Section: Introductionmentioning

confidence: 90%

“…In airways, including the nasal cavity, an increase in the amplitude (CBA) of ciliary beating in addition to the frequency (CBF) enhances the microbead transport driven by the ciliary beating . Recently, we developed a method to measure ciliary beat distance (CBD, an index of CBA) using a planner ciliated human nasal epithelial cells (cHNECs) in primary culture . Motile cilia have two functionally distinct molecular motors, namely, the inner dynein arms (IDA) controlling the waveform including CBD, and the outer dynein arms (ODA) controlling CBF .…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, a decrease in intracellular Cl − concentration ([Cl ‐ ] i ) coupled with cell shrinkage has been demonstrated to enhance CBA in cHNECs and lung airway ciliary cells . The [Cl ‐ ] i decrease is stimulated by the activation of Cl ‐ channels (Cl ‐ secretion) in airway ciliary cells …”

Section: Introductionmentioning

confidence: 99%

“…Carbocisteine (CCis), which has various actions, has been shown to stimulate nasal mucociliary clearance in patients contracting chronic sinusitis (CS) . In previous studies, CCis stimulates Cl ‐ secretion by activating Cl ‐ channels in airway epithelia . Moreover, CCis increased CBF and CBA via intracellular pH (pH i ) elevation and [Cl ‐ ] i decrease in lung airway ciliary cells …”

Section: Introductionmentioning

confidence: 99%

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Enhancement of ciliary beat amplitude by carbocisteine in ciliated human nasal epithelial cells

et al. 2019

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Objective: Carbocisteine (CCis), a mucoactive agent, is used to improve the symptoms of sinonasal diseases. However, the effect of CCis on nasal ciliary beating remains uncertain. We examined the effects of CCis on ciliary beat distance (CBD, an index of amplitude), and ciliary beat frequency (CBF) in ciliated human nasal epithelial cells (cHNECs) in primary culture.Methods: The cHNECs were prepared from the nasal tissue resected from patients required surgery for chronic sinusitis (CS) or allergic rhinitis (AR). CBD and CBF were measured using videomicroscopy equipped with a high-speed camera.Results: CCis increased CBD by 30%, but not CBF, and decreased intracellular Cl − concentration ([Cl − ] i ) in cHNECs. The CCis' actions were mimicked by the Cl − -free NO 3 − solution. In contrast, prior treatment of NPPB (20 μM) or CFTR(inh)-172 (1 μM), which increased [Cl − ] i by 20%, decreased CBF by 10% and CBD by 25% and inhibited the CCis' actions. However, prior treatment of T16Ainh-A01 (10 μM) did not inhibit the CCis' actions, although it decreased [Cl -] i by 10% and CBD by 15%. Thus, CCis stimulates Clchannels including cystic fibrosis transmembrane conductance regulator (CFTR). Moreover, CCis enhanced the transport of microbeads driven by the beating cilia in cHNECs. The CCis actions were similar in cHNECs from both types of pateints.Conclusion: CCis increased CBD by 30% in cHNECs via an [Cl − ] i decrease stimulated by activation of Cl − channels, including CFTR. CCis may stimulate nasal mucociliary clearance by increasing CBD in patients contracting CS or AR.

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“…The reagents were prepared to their final concentrations immediately before the experiments. DMSO concentration did not exceed 0.1% …”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 90%