Abstract
Sei-hai-to (TJ-90, Qing Fei Tang), a Chinese traditional medicine, increases ciliary beat frequency (CBF) and ciliary bend angle (CBA) mediated via cAMP (3′,5′-cyclic adenosine monophosphate) accumulation modulated by Ca2+-activated phosphodiesterase 1 (PDE1A). A high concentration of TJ-90 (≥40 μg/mL) induced two types of CBF increases, a transient increase (an initial increase, followed by a decrease) and a sustained increase without any decline, while it only sustained the CBA increase. Upon inhibiting increases in intracellular Ca2+ concentration ([Ca2+]i) by 10 μM BAPTA-AM (Ca2+-chelator, 1,2-Bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid tetrakis(acetoxymethyl ester) or Ca2+/calmodulin-dependent PDE1 by 8MmIBMX (a selective PDE1 inhibitor), TJ-90 (400 μg/mL) induced only the sustained CBF increase without any transient CBF increase. The two types of the CBF increase (the transient increase and the sustained increase) induced by TJ-90 (≥40 μg/mL) were mimicked by the stimulation with both procaterol (100 pM) and ionomycin (500 nM). Thus, TJ-90 stimulates small increases in the intracellular cAMP concentration ([cAMP]i) and [Ca2+]i in airway ciliary cells of mice. These small increases in [cAMP]i and [Ca2+]i cause inducing a transient CBF increase or a sustained CBF increase in an airway ciliary cells, depending on the dominant signal, Ca2+-signal, or cAMP-signal.
Highlights
The mucociliary clearance, which is conducted by the beating cilia cooperating with the surface mucous layer, is a host defense mechanism of the lungs
The ciliary beating is activated by an accumulation of cAMP and an increase in intracellular Ca2+ concentration ([Ca2+]i) [2,3,4]
Activities of the ciliary beating are assessed by two parameters, ciliary beat frequency (CBF) and ciliary bend angle (CBA) [12,13,14,15,16,17,18], and an increase in CBF or CBA has already been shown to activate the ciliary transport of the lung airway surface [12]
Summary
The mucociliary clearance, which is conducted by the beating cilia cooperating with the surface mucous layer, is a host defense mechanism of the lungs. The previous study revealed that TJ-90 increases ciliary beat frequency (CBF) and Cl− secretion in the rabbit trachea [9]. It remains uncertain how TJ-90 increases CBF and Cl− secretion in the airway epithelia. Activities of the ciliary beating are assessed by two parameters, CBF and CBA [12,13,14,15,16,17,18], and an increase in CBF or CBA has already been shown to activate the ciliary transport of the lung airway surface [12]. The goal of this study is to clarify the effects of TJ-90 on the CBF and CBA increases, especially the transient CBF increase
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