TY - JOUR
AU - Nakahari, Takashi
AB - 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%.
TI - Carbocisteine stimulated an increase in ciliary bend angle via a decrease in [Cl−]i in mouse airway cilia
JF - Pflügers Archiv European Journal of Physiologyl of Physiology
DO - 10.1007/s00424-018-2212-2
DA - 2018-10-06
UR - https://www.deepdyve.com/lp/springer-journals/carbocisteine-stimulated-an-increase-in-ciliary-bend-angle-via-a-tWNMmpU0Ns
SP - 365
EP - 380
VL - 471
IS - 2
DP - DeepDyve
ER -