Involvement of Neuronal Pathways in A1 Adenosine Receptor-Mediated Airway Hyperresponsiveness in a Murine Model of Allergic Asthma
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2010/05/01
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Description: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. [Description provided by NIOSH]
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ISSN:1073-449X
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Volume:181
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NIOSHTIC Number:nn:20037152
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Citation:Am J Respir Crit Care Med 2010 May; 181(Meeting Abstracts):A2832
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Federal Fiscal Year:2010
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Peer Reviewed:False
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Source Full Name:American Journal of Respiratory and Critical Care Medicine
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Supplement:Meeting Abstracts
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Main Document Checksum:urn:sha-512:a6a4f3f02759a5fadfd44858d9ac8deabf2051d33b8ec47c3f521e644204209e26b272a3345200eb6b2644cf8e18638db68642f3654bd792f39bbf4d7f2118b8
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