Methacholine-induced airway hyperresponsiveness is dependent on Gαq signaling
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. Gαq-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 Gαq-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 Gαq-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 Gαq-mediated signaling events and identify Gαq as a potential target of preventative/intervening therapies for lung dysfunction.
Publication Source (Journal or Book title)
American Journal of Physiology - Lung Cellular and Molecular Physiology
Borchers, M., Biechele, T., Justice, J., Ansay, T., Cormier, S., Mancino, V., Wilkie, T., Simon, M., Lee, N., & Lee, J. (2003). Methacholine-induced airway hyperresponsiveness is dependent on Gαq signaling. American Journal of Physiology - Lung Cellular and Molecular Physiology, 285 (1 29-1) https://doi.org/10.1152/ajplung.00322.2002