Action of N-acylated ambroxol derivatives on secretion of chloride ions in human airway epithelia |
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| Authors: | Takahiro Yamada Yoshizumi Takemura Naomi Niisato Etsuko Mitsuyama Yoshinobu Iwasaki Yoshinori Marunaka |
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| Affiliation: | 1. School of Health and Medical Sciences, University of Örebro, Örebro University Hospital, Örebro, Sweden;2. Clinical Epidemiology Unit, Department of Medicine, Karolinska Institutet, Solna, Sweden;1. Department of Experimental and Clinical Pharmacology, College of Pharmacy, University of Minnesota, 7-153 Weaver Densford Hall, 308 Harvard St SE, Minneapolis, MN 55455, United States;2. Department of Psychiatry, University of Minnesota, 2450 Riverside Ave, Minneapolis, MN 55454, United States;3. Masonic Cancer Center, University of Minnesota, Mayo Mail Code 806 420 Delaware Street SE, Minneapolis, MN 55455, United States;4. Tobacco Research Programs, University of Minnesota, 717 Delaware Street SE, Minnneapolis, MN 55414, United States;1. The Key Laboratory of Basic Pharmacology, School of Pharmaceutical Science, Nanchang University, Nanchang 330006, People''s Republic of China;2. Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, People''s Republic of China |
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| Abstract: | 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 hyper-secreting condition. |
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