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Am J Physiol Lung Cell Mol Physiol 288: L1139-L1145, 2005. First published February 4, 2005; doi:10.1152/ajplung.00406.2004
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Effect of 1,1-dimethylphenyl 1,4-piperazinium on mouse tracheal smooth muscle responsiveness

G. Dorion, E. Israël-Assayag, M. J. Beaulieu, and Y. Cormier

Unité de Recherche en Pneumologie, Centre de Recherche de l'Hôpital Laval, Institut Universitaire de Cardiologie et de Pneumologie de l'Université Laval, Sainte-Foy, Québec, Canada

Submitted 1 November 2004 ; accepted in final form 31 January 2005

Bronchial hyperresponsiveness is one of the main features of asthma. A nicotinic receptor agonist, 1,1-dimethylphenyl 1,4-piperazinium (DMPP), has been shown to have an inhibitory effect on airway response to methacholine in an in vivo model of asthma. The aims of this study were to 1) verify whether nicotinic acetylcholine receptors (nAChR) were present on mouse tracheal smooth muscle, 2) verify whether bronchoprotection observed in mice was due to a direct effect on airway smooth muscle, and 3) compare the effects of nicotinic agonists to that of salbutamol. {alpha}3-, {alpha}4-, and {alpha}7-nAChR subunits were detected by immunofluorescence on tracheal tissues from normal BALB/c mice. The effect of DMPP on tracheal responsiveness was verified by an isometric method. Tracheas were isolated from normal mice, placed in organ baths, and contracted with a single dose of methacholine. Cumulative doses of DMPP or salbutamol were added to the baths. Results show that mouse tracheal smooth muscle is positive for {alpha}4- and {alpha}7-nAChR subunits and that the epithelium is positive for {alpha}3-, {alpha}4-, and {alpha}7-subunits. DMPP induced a greater dose-dependent relaxation of tracheal smooth muscles precontracted with methacholine than with salbutamol. These results suggest that the smooth muscle-relaxing effect of DMPP could have some interest in the treatment of obstructive pulmonary diseases.

airway responsiveness; salbutamol; nicotinic agonists



Address for reprint requests and other correspondence: Y. Cormier, Hôpital Laval, 2725 Chemin Ste-Foy, Québec City, Québec, Canada G1V 4G5 (E-mail: yvon.cormier{at}crhl.ulaval.ca)




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M.-R. Blanchet, A. Langlois, E. Israel-Assayag, M.-J. Beaulieu, C. Ferland, M. Laviolette, and Y. Cormier
Modulation of eosinophil activation in vitro by a nicotinic receptor agonist
J. Leukoc. Biol., May 1, 2007; 81(5): 1245 - 1251.
[Abstract] [Full Text] [PDF]




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