title: Alteration of adenosine receptors in patients with chronic obstructive pulmonary disease.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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
  A(1), A(2A), A(2B), and A(3) receptors were expressed in different cells in peripheral lung parenchyma. The affinity of A(1), A(2A), and A(3) receptors was significantly decreased in patients with COPD compared with the control group (K(D)[A(1)] = 3.15 +/- 0.19 vs. 1.70 +/- 0.14 nM; K(D)[A(2A)] = 7.88 +/- 0.68 vs. 1.87 +/- 0.09 nM; K(D)[A(3)] = 9.34 +/- 0.27 vs. 4.41 +/- 0.25 nM; p < 0.01), whereas their density was increased (Bmax[A(1)] = 53 +/- 4 vs. 32 +/- 3 fmol/mg protein; Bmax[A(2A)] = 852 +/- 50 vs. 302 +/- 12 fmol/mg protein; Bmax[A(3)] = 2,078 +/- 108 vs. 770 +/- 34 fmol/mg protein; p < 0.01). The affinity of A(2B) 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 FEV(1)/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.
authors.affiliation: Department of Clinical and Experimental Medicine, Pharmacology Unit, Via Fossato di Mortara 17-19, 44100 Ferrara, Italy.
authors.forename: Katia
authors.initials: K
authors.lastname: Varani
authors.forename: Gaetano
authors.initials: G
authors.lastname: Caramori
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Vincenzi
authors.forename: Ian
authors.initials: I
authors.lastname: Adcock
authors.forename: Paolo
authors.initials: P
authors.lastname: Casolari
authors.forename: Edward
authors.initials: E
authors.lastname: Leung
authors.forename: Stephen
authors.initials: S
authors.lastname: Maclennan
authors.forename: Stefania
authors.initials: S
authors.lastname: Gessi
authors.forename: Silvana
authors.initials: S
authors.lastname: Morello
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ito
authors.forename: Kian Fan
authors.initials: KF
authors.lastname: Chung
authors.forename: Giorgio
authors.initials: G
authors.lastname: Cavallesco
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Azzena
authors.forename: Alberto
authors.initials: A
authors.lastname: Papi
authors.forename: Pier Andrea
authors.initials: PA
authors.lastname: Borea
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008168:Lung / Q000737:chemistry / Q000276:immunology; D008297:Male; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology*; D018047:Receptors, Purinergic P1 / Q000032:analysis* / Q000096:biosynthesis
chemical_list: D018047:Receptors, Purinergic P1