Hochu-ekki-to enhanced airway ciliary beating by an [Ca2+]i increase via TRPV4 in mice

Ikeuchi, Yoshihide; Kogiso, Haruka; Saito, Daichi; Kawaguchi, Kotoku; Ikeda, Riko; Asano, Shinji; Inui, Toshio; Marunaka, Yoshinori; Nakahari, Takashi

doi:10.1016/j.phyplu.2022.100243

Cited by 6 publications

(3 citation statements)

References 31 publications

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“…Ciliary movement in the airways is essential for the function of the body's defense system by expelling foreign substances that enter the airways from the body through dynein-driven mechanisms [ 157 ] via cAMP-mediated pathways [ 158 – 163 ], protein kinase C-mediated pathways [ 164 ] and cytosolic Ca 2+ -mediated pathways [ 166 , 167 ] in addition to water secretion from airway epithelia driven by Cl − secretion [ 88 ]. Cilia also play an important role in cerebrospinal flow [ 167 ].…”

Section: − -Regulatory Mechanisms Of Ciliary Motilitymentioning

confidence: 99%

Physiological roles of chloride ions in bodily and cellular functions

Marunaka

2023

J Physiol Sci

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Physiological roles of Cl−, a major anion in the body, are not well known compared with those of cations. This review article introduces: (1) roles of Cl− in bodily and cellular functions; (2) the range of cytosolic Cl− concentration ([Cl−]c); (3) whether [Cl−]c could change with cell volume change under an isosmotic condition; (4) whether [Cl−]c could change under conditions where multiple Cl− transporters and channels contribute to Cl− influx and efflux in an isosmotic state; (5) whether the change in [Cl−]c could be large enough to act as signals; (6) effects of Cl− on cytoskeletal tubulin polymerization through inhibition of GTPase activity and tubulin polymerization-dependent biological activity; (7) roles of cytosolic Cl− in cell proliferation; (8) Cl−-regulatory mechanisms of ciliary motility; (9) roles of Cl− in sweet/umami taste receptors; (10) Cl−-regulatory mechanisms of with-no-lysine kinase (WNK); (11) roles of Cl− in regulation of epithelial Na+ transport; (12) relationship between roles of Cl− and H+ in body functions.

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Section: − -Regulatory Mechanisms Of Ciliary Motilitymentioning

confidence: 99%

Physiological roles of chloride ions in bodily and cellular functions

Marunaka

2023

J Physiol Sci

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“…Before the start of experiments, the cells were perfused with the control solution for 5 min. After the experiments, the CBF and CBA were measured using an image analysis program (DippMotion 2D, Ditect, Tokyo, Japan) [16][17][18][19][20][21][22][23][24][25][26][27][28][29][22][23][24][25]. The CBF and CBA ratios (CBF t /CBF 0 and CBA t /CBA 0 ), the values of which were normalized by the control values, were used to make a comparison among the experiments.…”

Section: Cba and Cbf Measurementsmentioning

confidence: 99%

“…The procedure for western blotting has already been described in a previous report [36,17]. Protein (5-20 µg) obtained from isolated lung cells was loaded into each lane for Laemmli SDS-polyacrylamide gel electrophoresis (10%) and then transferred to a polyvinylidene di uoride membrane.…”

Section: Western Blottingmentioning

confidence: 99%

Ambroxol-enhanced frequency and amplitude of beating cilia mediated by pHi and [Cl-]i in lung airway epithelial cells of mice

Nakahari,

Suzuki,

Kawaguchi

et al. 2023

Preprint

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Ambroxol (ABX), a frequently prescribed secretolytic agent that stimulates Ca2+ release from acidic stores and Ca2+ entry through CaV1.2, enhanced the ciliary beat frequency (CBF) and ciliary bend angle (CBA, an index of amplitude) by 30% in ciliated lung airway epithelial cells (c-LAECs) of mice. An increase in the intracellular Ca2+ concentration ([Ca2+]i) stimulated by ABX triggers two signals in c-LAECs; an increase in pHi (pH pathway) and a decrease in [Cl-]i (Cl- pathway). The pH pathway, which was activated by the HCO3- entry through Na+-HCO3- cotransporter (NBC) and inhibited by 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS), enhanced the CBF (by 30%) and CBA (by 15-20%) and the Cl- pathway, which was activated by Cl- secretion through anoctamine 1 (ANO1) and inhibited by Cl- channel blockers (NPPB and T16Ainh), enhanced the CBA (by 10-15%). The enhancement of the CBF and CBA stimulated by ABX was decreased to 50% by a Ca2+-free solution or nifedipine (an inhibitor of L-type Ca2+ channels) and was abolished by BAPTA-AM in c-LAECs, indicating that an increase in [Ca2+]i stimulated by ABX is essential for activating the pH pathway and the Cl- pathway. The enhancement of CBF and CBA enhanced by ABX was mimicked by applying a CO2/HCO3--free Cl--free solution, which increased the pHi and decreased the [Cl-]i. In conclusion, ABX increased the CBF and CBA by 30% via the pH pathway and the Cl- pathway triggered by the [Ca2+]i increase in c-LAECs of mice.

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