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Elevated expression of adenosine A₁ receptor in bronchial biopsy specimens from asthmatic subjects

¹ Sackler Institute of Pulmonary Pharmacology, Division of Pharmaceutical Sciences, ² Dept of Asthma and Allergy, Division of Medicine, King’s College London, London, and ³ GlaxoSmithKline, Stevenage, UK.

CORRESPONDENCE: C. P. Page, King’s College London, Sackler Institute of Pulmonary Pharmacology 5th floor, Hodgkin Building, Guy’s Campus, London, SE1 1UL, UK. Fax: 44 2078486097. E-mail: clive.page{at}kcl.ac.uk

Keywords: Adenosine, adenosine A₁ receptor, adenosine A₁ receptor expression, asthma

Received: January 11, 2007
Accepted September 27, 2007

Asthmatics, unlike healthy subjects, experience bronchoconstriction in response to inhaled adenosine, and extracellular adenosine concentrations are elevated in the bronchoalveolar lavage fluid and exhaled breath condensate of asthmatic subjects. However, little is known about the location and expression of adenosine receptors in asthmatic airways. The aim of the present study was to investigate the distribution of adenosine A₁ receptors in bronchial biopsy specimens from mildly asthmatic steroid-naïve subjects and then compare the degree of expression with that of healthy subjects.

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

Immunostaining of biopsy sections from the asthmatic subjects revealed strong expression of the A₁ receptor, located predominantly in the bronchial epithelium and bronchial smooth muscle. In comparison, very weak immunostaining was observed in biopsy specimens obtained from healthy subjects. Image analysis revealed that the intensity of positive staining of the asthmatic bronchial epithelium and smooth muscle regions was significantly greater than that observed for the healthy epithelium and smooth muscle.

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

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