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A3 adenosine receptor signaling contributes to airway mucin secretion after allergen challenge. | LitMetric

A3 adenosine receptor signaling contributes to airway mucin secretion after allergen challenge.

Am J Respir Cell Mol Biol

Department of Biochemistry and Molecular Biology, University of Texas Health Science Center at Houston, Medical School, 6431 Fannin, Houston, TX 77030, USA.

Published: November 2006

AI Article Synopsis

Article Abstract

Mucin hypersecretion is a prominent feature of obstructive airway diseases such as asthma. Clara cells conditionally produce mucin in response to inflammatory signals in a process termed mucous metaplasia. This can be followed by mucin secretion stimulated by various signaling molecules. The cellular and molecular mechanisms that regulate mucin production and secretion are not well understood. Adenosine is a signaling nucleoside that has been implicated in airway diseases in which mucus obstruction is prominent. Furthermore, the A(3) adenosine receptor (A(3)AR) is upregulated in mucin-producing goblet cells of the airway, thereby implicating it in processes involved in mucous cell biology. Here we use genetic approaches to investigate the contribution of A(3)AR signaling to mucus production and secretion in a mouse model of allergen-induced pulmonary disease. We found that the degree of mucin production in response to allergen is similar in wild-type and A(3)AR-deficient mice, and that overexpression of this receptor in Clara cells neither induces mucin production itself, nor enhances mucin production in response to allergen challenge. Collectively, these experiments demonstrate that the A(3)AR is neither necessary nor sufficient for mucous cell metaplasia. In contrast to the lack of effect on mucin production, agonist-induced mucin secretion was increased in goblet cells overexpressing the A(3)AR, and was absent in A(3)AR-deficient mice. Thus, the A(3)AR contributes to mucin secretion in allergen-induced metaplasia. Signaling through this receptor may contribute to mucus airway obstruction seen in pulmonary disorders in which adenosine levels are elevated.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2643274PMC
http://dx.doi.org/10.1165/rcmb.2006-0060OCDOI Listing

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