Action of N-acylated ambroxol derivatives on secretion of chloride ions in human airway epithelia

作者：Yamada Takahiro; Takemura Yoshizumi; Niisato Naomi; Mitsuyama Etsuko; Iwasaki Yoshinobu; Marunaka Yoshinori^*

来源：Biochemical and Biophysical Research Communications, 2009, 380(3): 586-590.

DOI：10.1016/j.bbrc.2009.01.122

• Ion transport
• Calu-3 cells
• CFTR
• beta(2)-adrenergic agonist
• Ambroxol

We report the effects of new N-acylated ambroxol derivatives (TEI-588a, TEI-588b, TEI-589a, TEI-589b, TEI-602a and TEI-602b: a, aromatic amine-acylated derivative; b, aliphatic amine-acylated derivative) induced from ambroxol (a mucolytic agent to treat human lung diseases) on Cl(-) secretion in human submucosal serous Calu-3 cells under a Na( )/K( )/2Cl(-) cotransporter-1 (NKCC1)-mediated hyper-secreting condition. TEI-589a, TEI-589b and TEI-602a diminished hyper-secretion of Cl(-) by diminishing the activity of NKCC1 without blockade of apical Cl(-) channel (TEI-589a > TEI-602a > TEI-589b), while any other tested Compounds including ambroxol had no effects on Cl- secretion. These indicate that the inhibitory action of an aromatic amine-acylated derivative on Cl- secretion is stronger that that of an aliphatic amine-acylated derivative, and that 3-(2,5-dimethyl)furoyl group has a strong action in inhibition of Cl(-) secretion than cyclopropanoyl group. We here indicate that TEI-589a, TEI-589b and TEI-602a reduce hyper-secretion to an appropriate level in the airway, providing a possibility that the compound can be an effective drug in airway obstructive diseases including COPD by reducing the airway resistance under a hypersecreting condition.

• 出版日期2009-3-13