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Involvement of neuronal pathways in A1 adenosine receptor-mediated airway hyperresponsiveness in a murine model of allergic asthma.
Young-EJ; Wu-ZX; Ponnoth-DS; Mustafa-SJ
Am J Respir Crit Care Med 2010 May; 181(Meeting Abstracts):A2832
Rationale: The ability of adenosine to induce airway hyperresponsiveness in asthmatic mice through its effect on four extra-cellular adenosine receptors is well documented. Specifically, the A1 adenosine receptor has been shown to have a pro-inflammatory effect and to induce hyperresponsiveness in an allergic rabbit model of asthma (Nadeem, A, et al. 2006, Eur J Pharmacol, 551, 116-24). Recently, the A1 adenosine receptor has been implicated in inducing airway hyperresponsivness through neuronal pathways in naive, non-allergic mice (Hua, X et al., 2007, Am J Physiol Lung Cell Mol Physiol., 293(1):L25-32). It remains unknown whether such a mechanism is involved in the allergic mouse model of asthma. Methods: In our study, C57 mice were sensitized to allergen by 200 ug injections of ragweed extract in alum on days 1 and 6 and challenged with 1% ragweed aerosol on days 11-13 of a two week allergen protocol (Fan, M, and Mustafa, SJ, 2002, Pulm Pharmacol Ther 15: 147-155.). On day 14, pulmonary resistance in response to aerosolized adenosine, 6 mg/ml was recorded with or without 20 mu mol/kg atropine pretreatment. Results: Control animals received only alum injections and saline aerosol. Pretreatment with atropine significantly decreased (p<0.05) the pulmonary response to adenosine in the sensitized and challenged mouse (176 +/- 60% of the response to vehicle in the untreated allergic mouse versus 110 +/- 10% in the atropine treated allergic mouse, n=5-6). Conclusion: These data indicate a cholinergic route for the activity of adenosine in allergic asthma, supporting a role for vagal neuronal pathways in this allergic mouse model of asthma.
Aerosol-particles; Airborne-particles; Airway-obstruction; Allergens; Biological-effects; Biological-monitoring; Exposure-assessment; Exposure-levels; Exposure-methods; Inhalation-studies; Laboratory-animals; Laboratory-techniques; Laboratory-testing; Lung; Lung-irritants; Particle-aerodynamics; Particulate-dust; Particulates; Pulmonary-system; Pulmonary-system-disorders; Respiratory-hypersensitivity; Respiratory-infections; Respiratory-irritants; Respiratory-system-disorders; Risk-analysis; Statistical-analysis
American Journal of Respiratory and Critical Care Medicine
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