A Synthetic Chloride Channel Relaxes Airway Smooth Muscle of the Rat

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.

Anion Transport with Halogen Bonds

“…This cooperative multiion hopping across lipid bilayer membranes is essential to combine selectivity with speed, is ubiquitous in biological ion channel and was the key to create the first anion channel that operates with halogen bonds (see below). More recently, the transport of anions across bilayer membranes moved more into focus, also because of possible medicinal use with regard to cystic fibrosis and related channelopathies [7][8][9][10][11]. Other attractive applications of anion transport include separation and purification systems, sensing [12], artificial photosynthesis [13] [14], catalysis [15], drug delivery [16], and so on.…”

“…The leading nonpeptide example from biology for anion transport is prodigiosin 8, a red pigment produced by certain bacteria (Fig. 2) [7][8][9][10][11]. Many prodigiosin mimics have been reported.…”