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Published ahead of print on December 1, 2005, doi:10.1164/rccm.200506-869OC

Am. J. Respir. Crit. Care Med., Volume 173, Number 4, February 2006, 398-406

A more recent version of this article appeared on February 15, 2006
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Submitted on June 6, 2005
Accepted on November 28, 2005

Alteration of Adenosine Receptors in Patients with Chronic Obstructive Pulmonary Disease

Katia Varani1, Gaetano Caramori2, Fabrizio Vincenzi1, Ian Adcock3, Paolo Casolari2, Edward Leung4, Stephen MacLennan4, Stefania Gessi1, Silvana Morello3, Peter J Barnes3, Kazuhiro Ito3, Kian Fan Chung3, Giorgio Cavallesco5, Gianfranco Azzena5, Alberto Papi2, and Pier Andrea Borea1*

1 Department of Clinical and Experimental Medicine, Pharmacology Section, University of Ferrara, Ferrara, Italy, 2 Department of Clinical and Experimental Medicine, Respiratory Disease Section, University of Ferrara, Ferrara, Italy, 3 Airway Disease Section, NHLI Imperial College London, London, United Kingdom, 4 King Pharmaceuticals, Cary, NC, USA, 5 Department of Surgical Sciences, Thoracic Surgery Section, University of Ferrara, Ferrara, Italy

* To whom correspondence should be addressed. E-mail: bpa{at}unife.it.

Rationale: Chronic obstructive pulmonary disease (COPD) is the fourth leading cause of mortality worldwide. Adenosine is an inflammatory regulatory which acts through four distinct receptors to mediates pro- and -anti-inflammatory effects. Objectives: The primary aim of this study is 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 COPD patients compared with control group [KD(A1)=3.15±0.19* versus 1.70±0.14 nM; KD(A2A)=7.88±0.68* versus 1.87±0.09 nM; KD(A3)=9.34±0.27* versus 4.41±0.25 nM; *p<0.01] whereas their density was increased [Bmax(A1)=53±4* versus 32±3 fmol/mg protein; Bmax(A2A)=852±50* versus 302±12 fmol/mg protein; Bmax(A3)=2078±108* versus 770±34 fmol/mg protein; *p<0.01]. The affinity of A2B receptors was not altered but the density was significantly decreased in COPD patients compared with the control group (Bmax=66±5* versus 189±16 fmol/mg protein; *p<0.01). A significant correlation was found between the affinity and density of the adenosine receptors and forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) ratio. Conclusions: This is the first report showing the presence of adenosine receptors in lung parenchyma in 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: chronic obstructive pulmonary disease, adenosine receptors, inflammation, small airways.




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