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

Autor: Saori Tanaka, Haruka Kogiso, Chikao Shimamoto, Hitoshi Matsumura, Shigekuni Hosogi, Takashi Nakahari, Toshio Inui, Yoshinori Marunaka, Yukiko Ikeuchi
Rok vydání: 2018
Předmět:
Zdroj: Pflügers Archiv - European Journal of Physiology. 471:365-380
ISSN: 1432-2013
0031-6768
DOI: 10.1007/s00424-018-2212-2
Popis: 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%.
Databáze: OpenAIRE
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