Effect of 1,1-dimethylphenyl 1,4-piperazinium on mouse tracheal smooth muscle responsiveness.

Abstract

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. Alpha3-, alpha4-, and alpha7-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 alpha4- and alpha7-nAChR subunits and that the epithelium is positive for alpha3-, alpha4-, and alpha7-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.

• Authors: G Dorion, E Israël-Assayag, M J Beaulieu, Y Cormier
• Journal: American journal of physiology. Lung cellular and molecular physiology (Am J Physiol Lung Cell Mol Physiol) Vol. 288 Issue 6 Pg. L1139-45 (Jun 2005) ISSN: 1040-0605 [Print] United States
• PMID: 15695540 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Bronchoconstrictor Agents
• Bronchodilator Agents
• Chrna7 protein, mouse
• Nicotinic Agonists
• Receptors, Nicotinic
• alpha7 Nicotinic Acetylcholine Receptor
• nicotinic acetylcholine receptor alpha4 subunit
• nicotinic receptor subunit alpha3
• Methacholine Chloride
• Dimethylphenylpiperazinium Iodide
• Albuterol

Topics

• Albuterol (pharmacology)
• Animals
• Bronchoconstrictor Agents (pharmacology)
• Bronchodilator Agents (pharmacology)
• Dimethylphenylpiperazinium Iodide (pharmacology)
• Epithelium (drug effects)
• Female
• Methacholine Chloride (pharmacology)
• Mice
• Mice, Inbred BALB C
• Muscle Relaxation (drug effects)
• Muscle, Smooth (drug effects, innervation)
• Nicotinic Agonists (pharmacology)
• Receptors, Nicotinic (metabolism)
• Trachea (drug effects, innervation)
• alpha7 Nicotinic Acetylcholine Receptor