A synthetic chloride channel relaxes airway smooth muscle of the rat.
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.
Morningside Laboratory for Chemical Biology, Department of Chemistry, Faculty of Science, The University of Hong Kong, Hong Kong SAR, China.
Kwok-hei
KH
Yau
Judith Choi-wo
JC
Mak
Susan Wai-sum
SW
Leung
Dan
D
Yang
Paul M
PM
Vanhoutte
D000818:Animals; D000838:Anions; D000001:Calcimycin / Q000494:pharmacology; D061207:Calcium Ionophores / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000138:chemical synthesis* / Q000378:metabolism*; D002712:Chlorides / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000037:antagonists & inhibitors / Q000378:metabolism; D019332:Endothelin-1 / Q000494:pharmacology; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008916:Miotics / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D046509:Tissue Culture Techniques; D014132:Trachea / Q000187:drug effects / Q000378:metabolism*
D000838:Anions; D061207:Calcium Ionophores; D018118:Chloride Channels; D002712:Chlorides; D019332:Endothelin-1; D008916:Miotics; D017366:Serotonin Receptor Agonists; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D012701:Serotonin; D000001:Calcimycin; D011189:Potassium Chloride; D002217:Carbachol