title: s-Carboxymethylcysteine inhibits carbachol-induced constriction of epithelium-denuded rat and human airway preparations.
abstract: 1. The effects of s-carboxymethyl-L-cysteine (S-CMC), either administered orally to rats or incubated with tissue preparations from rats and humans, on isometric contractions of tracheal smooth muscle were investigated in the present study using an improved in vitro model of tracheal tube or ring preparations. The involvement of the tracheal epithelium in the observed effects was also investigated. 2. The experimental model permitted selective perfusion of the airway tube, luminal-IN or serosal-OUT, and measurement of airway smooth muscle contraction or relaxation in preparations with (+) or without (-) epithelium (Ep), excluding direct effects of airway mucus. 3. We found that oral pretreatment of rats with S-CMC (mixed with water; 200 mg/kg per day for 2 weeks), but not short pre-incubation of preparations in vitro (10(-3) mol/L S-CMC for 1 h), diminished the sensitivity of -Ep preparations to carbachol compared with controls (EC(50) (-log(10) mol/L) values: 5.5 +/- 0.1 vs 5.8 +/- 0.1, respectively, for IN perfusion (P < 0.005); 5.6 +/- 0.1 vs 5.9 +/- 0.1, respectively, for OUT perfusion (P < 0.005)), whereas the sensitivity of preparations to aminophylline was not affected. Normal sensitivity to carbachol stimulation was re-established if preparations were pre-incubated with capsaicin. 4. It was also found that longer pre-incubation (4 h) of ring-preparations of human bronchus with S-CMC (10(-5) mol/L) in vitro resulted in a diminished response to carbachol stimulation. 5. In conclusion, S-CMC had small inhibitory effects on the sensitivity of rat and human airway smooth muscle to carbachol, particularly in endothelium-denuded preparations. Whether the epithelium was responding to S-CMC by producing some contracting factor(s) requires further investigation.
authors.affiliation: Department of Anaesthesiology and Intensive Care Medicine, Ernst-Moritz-Arndt University, Greifswald, Germany. pavlovic@uni-greifswald.de
authors.forename: Dragan
authors.initials: D
authors.lastname: Pavlovic
authors.forename: Helge
authors.initials: H
authors.lastname: Frieling
authors.forename: Taras
authors.initials: T
authors.lastname: Usichenko
authors.forename: Vladimir
authors.initials: V
authors.lastname: Nedeljkov
authors.forename: Thais
authors.initials: T
authors.lastname: Nafissi
authors.forename: Christian
authors.initials: C
authors.lastname: Lehmann
authors.forename: Michel
authors.initials: M
authors.lastname: Aubier
authors.forename: Michael
authors.initials: M
authors.lastname: Wendt
mesh_terms: D000818:Animals; D016084:Bronchoconstriction / Q000187:drug effects*; D002217:Carbachol / Q000494:pharmacology*; D002233:Carbocysteine / Q000008:administration & dosage / Q000494:pharmacology*; D006801:Humans; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D020545:Respiratory Mucosa / Q000502:physiology*; D014132:Trachea / Q000187:drug effects / Q000502:physiology
chemical_list: D002233:Carbocysteine; D002217:Carbachol