title: Role of m2 muscarinic receptor in the airway response to methacholine of mice selected for minimal or maximal acute inflammatory response.
abstract: 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.
authors.affiliation: Department of Immunology, Institute of Biomedical Sciences, University of São Paulo, 05508-000 São Paulo, Brazil.
authors.forename: Juciane Maria de Andrade
authors.initials: JM
authors.lastname: Castro
authors.forename: Rodrigo R
authors.initials: RR
authors.lastname: Resende
authors.forename: Luciana
authors.initials: L
authors.lastname: Mirotti
authors.forename: Esther
authors.initials: E
authors.lastname: Florsheim
authors.forename: Layra Lucy
authors.initials: LL
authors.lastname: Albuquerque
authors.forename: Adriana
authors.initials: A
authors.lastname: Lino-dos-Santos-Franco
authors.forename: Eliane
authors.initials: E
authors.lastname: Gomes
authors.forename: Wothan Tavares
authors.initials: WT
authors.lastname: de Lima
authors.forename: Marcelo
authors.initials: M
authors.lastname: de Franco
authors.forename: Orlando Garcia
authors.initials: OG
authors.lastname: Ribeiro
authors.forename: Momtchilo
authors.initials: M
authors.lastname: Russo
mesh_terms: D000818:Animals; D006967:Hypersensitivity / Q000150:complications / Q000473:pathology; D066298:In Vitro Techniques; D016210:Methacholine Chloride / Q000494:pharmacology*; D051379:Mice; D008954:Models, Biological; D011014:Pneumonia / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D043585:Receptor, Muscarinic M2 / Q000378:metabolism*; D043587:Receptor, Muscarinic M3 / Q000378:metabolism; D012119:Respiration / Q000187:drug effects; D014132:Trachea / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology
chemical_list: D043585:Receptor, Muscarinic M2; D043587:Receptor, Muscarinic M3; D016210:Methacholine Chloride