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 HCO(3) (-). 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Anions
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Calcimycin / pharmacology
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Calcium Ionophores / pharmacology
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Carbachol / pharmacology
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Chloride Channels / antagonists & inhibitors
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Chloride Channels / chemical synthesis*
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Chloride Channels / metabolism*
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Chlorides / pharmacology
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Cystic Fibrosis Transmembrane Conductance Regulator / antagonists & inhibitors
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Cystic Fibrosis Transmembrane Conductance Regulator / metabolism
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Endothelin-1 / pharmacology
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Isometric Contraction / drug effects
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Male
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Miotics / pharmacology
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Muscle Relaxation / drug effects*
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Muscle, Smooth / drug effects
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Muscle, Smooth / metabolism*
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Potassium Chloride / pharmacology
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Rats
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Rats, Sprague-Dawley
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Serotonin / pharmacology
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Serotonin Receptor Agonists / pharmacology
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Tissue Culture Techniques
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Trachea / drug effects
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Trachea / metabolism*
Substances
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Anions
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Calcium Ionophores
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Chloride Channels
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Chlorides
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Endothelin-1
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Miotics
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Serotonin Receptor Agonists
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Cystic Fibrosis Transmembrane Conductance Regulator
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Serotonin
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Calcimycin
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Potassium Chloride
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Carbachol
Grants and funding
This study was supported by grants from the University of Hong Kong and the Hong Kong Research Grants Council Collaborative Research Fund (HKU2/06C and HKU8/CRF/10). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.