Ambroxol-induced modification of ion transport in human airway Calu-3 epithelia
Ambroxol-induced modification of ion transport in human airway Calu-3 epithelia
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DOI：
10.1016/j.bbrc.2006.03.009
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发表时间：
2006-05-05
影响因子：
3.1
通讯作者：
Marunaka, Y
中科院分区：
文献类型：
--
作者：
Hasegawa, I;Niisato, N;Marunaka, Y
氨溴索常用作各种肺部疾病的粘液溶解剂。然而，氨溴索如何作用于支气管上皮细胞尚不清楚。为了阐明氨溴索的作用，我们研究了氨溴索对人Calu-3细胞（一种人粘膜下浆液性细胞）离子转运的影响，测量了跨Calu-3细胞单层的跨上皮短路电流和电导。100 μ M的氨溴索减少了特布他林（β（2）-肾上腺素能激动剂）刺激的Cl-/HCO 3-依赖性分泌，而不降低位于顶膜上的囊性纤维化跨膜传导调节因子（CFTR）通道的传导。另一方面，在基础（未刺激）条件下，氨溴索增加了Cl-依赖性分泌，而顶端CFTR通道电导无显著变化，并减少了与顶端CFTR通道电导降低相关的HCO 3-分泌。氨溴索对上皮Na+通道（ENaC）或ENaC介导的Na+吸收无重大作用。这些结果表明，在Calu-3细胞中：（1）在基础（未刺激）条件下，氨溴索通过刺激Cl-进入步骤增加Cl-分泌，通过降低CFTR通道和/或Na+/HCO 3-依赖性协同转运蛋白的活性减少HCO 3-分泌，（2）在肾上腺素能激动剂刺激条件下，氨溴索通过作用于Cl-/HCO 3-交换剂减少Cl-分泌，和（3）氨溴索对Cl-/HCO 3-交换的作用比肾上腺素能激动剂更强，可使液体分泌从过度刺激水平达到中度刺激水平。(c)2006年爱思唯尔公司All rights reserved.
Ambroxol is often used as a mucolytic agent in various lung diseases. However, it is unclear how ambroxol acts on bronchial epithelial cells. To clarify the action of ambroxol, we studied the effects of ambroxol on the ion transport in human Calu-3 cells, a human submucosal serous cell title, measuring the transepithelial short-circuit current and conductance across monolayers of Calu-3 cells. Ambroxol of 100 mu M diminished the terbutaline (a beta(2)-adrenergic agonist)-stimulated Cl-/HCO3--dependent secretion without any decreases in the conductance of cystic fibrosis transmembrane conductance regulator (CFTR) channel locating on the apical membrane. On the other hand, under the basal (unstimulated) condition ambroxol increased the Cl--dependent secretion with no significant change in the apical CFTR channel conductance and decreased the HCO3- secretion associated with a decrease in the apical CFTR channel conductance. Ambroxol had no major action on the epithelial Na+ channel (ENaC) or the ENaC-mediated Na+ absorption. These results indicate that in Calu-3 cells: (1) under the basal (unstimulated) condition ambroxol increases Cl- secretion by stimulating the entry step of Cl- and decreases HCO3- secretion by diminishing the activity of the CFTR channel and/or the Na+/HCO3--dependent cotransporter, (2) under the adrenergic agonist-stimulated condition, ambroxol decreases Cl- secretion by acting on the Cl-/HCO3- exchanger, and (3) ambroxol has a more powerful action than the adrenergic agonist on the Cl-/HCO3- exchanger, leading fluid secretion to a moderately stimulated level from a hyper-stimulated level. (c) 2006 Elsevier Inc. All rights reserved.