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Published ahead of print on December 1, 2005, doi:10.1164/rccm.200506-869OC
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American Journal of Respiratory and Critical Care Medicine Vol 173. pp. 398-406, (2006)
© 2006 American Thoracic Society
doi: 10.1164/rccm.200506-869OC

Original Article

Alteration of Adenosine Receptors in Patients with Chronic Obstructive Pulmonary Disease

Katia Varani*, Gaetano Caramori*, Fabrizio Vincenzi, Ian Adcock, Paolo Casolari, Edward Leung, Stephen MacLennan, Stefania Gessi, Silvana Morello, Peter J. Barnes, Kazuhiro Ito, Kian Fan Chung, Giorgio Cavallesco, Gianfranco Azzena, Alberto Papi* and Pier Andrea Borea*

Department of Clinical and Experimental Medicine, Pharmacology Section, and Department of Clinical and Experimental Medicine, Respiratory Disease Section, and Department of Surgical Sciences, Thoracic Surgery Section, University of Ferrara, Ferrara, Italy; King Pharmaceuticals, Cary, North Carolina; and Airway Disease Section, National Heart and Lung Institute, Imperial College London, United Kingdom

Correspondence and requests for reprints should be addressed to Prof. Pier Andrea Borea, Ph.D., Department of Clinical and Experimental Medicine, Pharmacology Unit, Via Fossato di Mortara 17-19 44100, Ferrara, Italy. E-mail: bpa{at}unife.it

Rationale: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of mortality worldwide. Adenosine is an inflammatory regulator that acts through four distinct receptors to mediate pro- and antiinflammatory effects.

Objectives: The primary aim of this study was to investigate the expression, affinity, and density of adenosine receptors in peripheral lung parenchyma from age-matched smokers with COPD (n = 14) and smokers with normal lung function (control group; n = 20).

Methods: Adenosine receptors were analyzed by immunohistochemistry and saturation binding assays using typical antagonist radioligands.

Results: A1, A2A, A2B, and A3 receptors were expressed in different cells in peripheral lung parenchyma. The affinity of A1, A2A, and A3 receptors was significantly decreased in patients with COPD compared with the control group (KD[A1] = 3.15 ± 0.19 vs. 1.70 ± 0.14 nM; KD[A2A] = 7.88 ± 0.68 vs. 1.87 ± 0.09 nM; KD[A3] = 9.34 ± 0.27 vs. 4.41 ± 0.25 nM; p < 0.01), whereas their density was increased (Bmax[A1] = 53 ± 4 vs. 32 ± 3 fmol/mg protein; Bmax[A2A] = 852 ± 50 vs. 302 ± 12 fmol/mg protein; Bmax[A3] = 2,078 ± 108 vs. 770 ± 34 fmol/mg protein; p < 0.01). The affinity of A2B receptors was not altered, but the density was significantly decreased in patients with COPD compared with the control group (Bmax = 66 ± 5 vs. 189 ± 16 fmol/mg protein; p < 0.01). A significant correlation was found between the affinity and density of the adenosine receptors and the FEV1/FVC ratio.

Conclusions: This is the first report showing the presence of adenosine receptors in lung parenchyma in subjects with COPD compared with control smokers. These novel findings strengthen the hypothesis of a potential role played by adenosine receptors in the pathogenesis of COPD.

Key Words: adenosine receptors • chronic obstructive pulmonary disease • inflammation • small airways




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