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BioMed Research International
Volume 2013 (2013), Article ID 805627, 12 pages
Research Article

Role of M2 Muscarinic Receptor in the Airway Response to Methacholine of Mice Selected for Minimal or Maximal Acute Inflammatory Response

1Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil
2Cell Signaling and Nanobiotechnology Laboratory, Department of Biochemistry and Immunology, Federal University of Minas Gerais, Minas Gerais, 31270-901 Belo Horizonte, Brazil
3Laboratory of Imunogenetics, Instituto Butantan, 05503-900 São Paulo, Brazil
4Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, 05508-900 São Paulo, Brazil

Received 3 December 2012; Revised 16 February 2013; Accepted 18 February 2013

Academic Editor: Alexandre de Paula Rogerio

Copyright © 2013 Juciane Maria de Andrade Castro et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Airway smooth muscle constriction induced by cholinergic agonists such as methacholine (MCh), which is typically increased in asthmatic patients, is regulated mainly by muscle muscarinic M3 receptors and negatively by vagal muscarinic M2 receptors. Here we evaluated basal (intrinsic) and allergen-induced (extrinsic) airway responses to MCh. We used two mouse lines selected to respond maximally (AIRmax) or minimally (AIRmin) to innate inflammatory stimuli. We found that in basal condition AIRmin mice responded more vigorously to MCh than AIRmax. Treatment with a specific M2 antagonist increased airway response of AIRmax but not of AIRmin mice. The expression of M2 receptors in the lung was significantly lower in AIRmin compared to AIRmax animals. AIRmax mice developed a more intense allergic inflammation than AIRmin, and both allergic mouse lines increased airway responses to MCh. However, gallamine treatment of allergic groups did not affect the responses to MCh. Our results confirm that low or dysfunctional M2 receptor activity is associated with increased airway responsiveness to MCh and that this trait was inherited during the selective breeding of AIRmin mice and was acquired by AIRmax mice during allergic lung inflammation.