Methacholine-induced airway hyperresponsiveness is dependent on Galphaq signaling.

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Borchers MT, Biechele T, Justice JP, Ansay T, Cormier S, Mancino V, Wilkie TM, Simon MI, Lee NA, Lee JJ

Methacholine-induced airway hyperresponsiveness is dependent on Galphaq signaling.

Am J Physiol Lung Cell Mol Physiol. 2003 Jul;285(1):L114-20. doi: 10.1152/ajplung.00322.2002. Epub 2003 Feb 28.

PubMed ID

12611815 [ View in PubMed

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Abstract

Airway function in health and disease as well as in response to bronchospastic stimuli (i.e., irritants, allergens, and inflammatory mediators) is controlled, in part, by cholinergic muscarinic receptor regulation of smooth muscle. In particular, the dependence of airway smooth muscle contraction/relaxation on heterotrimeric G protein-coupled receptor signaling suggests that these events underlie the responses regulating airway function. Galphaq-containing G proteins are proposed to be a prominent signaling pathway, and the availability of knockout mice deficient of this subunit has allowed for an investigation of its potential role in airway function. Airway responses in Galphaq-deficient mice (activities assessed by both tracheal tension and in vivo lung function measurements) were attenuated relative to wild-type controls. Moreover, ovalbumin sensitization/aerosol challenge of Galphaq-deficient mice also failed to elicit an allergen-induced increase in airway reactivity to methacholine. These findings indicate that cholinergic receptor-mediated responses are dependent on Galphaq-mediated signaling events and identify Galphaq as a potential target of preventative/intervening therapies for lung dysfunction.

DrugBank Data that Cites this Article

Drugs

Methacholine

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Methacholine	Muscarinic acetylcholine receptor M3	Protein	Humans	Yes	Agonist	Details