Elevated expression of adenosine A1 receptor in bronchial biopsies from asthmatic subjects

¹ King's College London, Sackler Institute of Pulmonary Pharmacology, Division of Biomedical and Health Sciences, London, United Kingdom
² King's College London, Dept of Asthma and Allergy, Division of Medicine, London, United Kingdom
³ GlaxoSmithKline, Stevenage, United Kingdom

^* To whom correspondence should be addressed. E-mail: clive.page{at}kcl.ac.uk.

	Abstract

Asthmatics, unlike healthy subjects, bronchoconstrict in response to inhaled adenosine and extracellular adenosine concentrations are elevated in bronchoalveolar lavage fluid and exhaled breath condensate of asthmatic subjects. However, little is understood about the location and expression of adenosine receptors in asthmatic airways. Our aim was to first investigate the distribution of adenosine A₁ receptors in bronchial biopsies from mild asthmatic steroid-naïve subjects and then compare the degree of expression with healthy subjects.

Biopsy sections were immunostained with an adenosine A₁ receptor antibody, the selectivity of which was validated in specific experiments. Image analysis was then performed to determine differences in immunostaining intensity.

Immunostaining of biopsies from the asthmatic subjects revealed strong expression of the A₁ receptor located predominantly to the bronchial epithelium and bronchial smooth muscle. In comparison, very weak immunostaining was observed in biopsies obtained from healthy subjects. Image analysis revealed that the intensity of positive staining on the asthmatic bronchial epithelium and smooth muscle regions was significantly greater than that observed with the healthy epithelium and smooth muscle (P<0.01).

In conclusion, the sensitivity of asthmatics to inhaled adenosine coupled with increased adenosine A₁ receptor expression implicates a role for these receptors in the pathophysiology of this disease.

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