A Synthetic Chloride Channel Relaxes Airway Smooth Muscle of the Rat |
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| Authors: | Kwok-hei Yau Judith Choi-wo Mak Susan Wai-sum Leung Dan Yang Paul M. Vanhoutte |
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| Affiliation: | 1. Morningside Laboratory for Chemical Biology, Department of Chemistry, Faculty of Science, The University of Hong Kong, Hong Kong SAR, China.; 2. Department of Pharmacology and Pharmacy, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.; 3. Department of Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China.; The Chinese University of Hong Kong, Hong Kong, |
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| Abstract: | Synthetic ion channels may have potential therapeutic applications, provided they possess appropriate biological activities. The present study was designed to examine the ability of small molecule-based synthetic Cl– channels to modulate airway smooth muscle responsiveness. Changes in isometric tension were measured in rat tracheal rings. Relaxations to the synthetic chloride channel SCC-1 were obtained during sustained contractions to KCl. The anion dependency of the effect of SCC-1 was evaluated by ion substitution experiments. The sensitivity to conventional Cl– transport inhibitors was also tested. SCC-1 caused concentration-dependent relaxations during sustained contractions to potassium chloride. This relaxing effect was dependent on the presence of extracellular Cl– and HCO3−. It was insensitive to conventional Cl– channels/transport inhibitors that blocked the cystic fibrosis transmembrane conductance regulator and calcium-activated Cl– channels. SCC-1 did not inhibit contractions induced by carbachol, endothelin-1, 5-hydroxytryptamine or the calcium ionophore A23187. SCC-1 relaxes airway smooth muscle during contractions evoked by depolarizing solutions. The Cl– conductance conferred by this synthetic compound is distinct from the endogenous transport systems for chloride anions. |
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