Alteration of adenosine receptors in patients with chronic obstructive pulmonary disease.
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.
Varani
Katia
K
Department of Clinical and Experimental Medicine, Pharmacology Unit, Via Fossato di Mortara 17-19, 44100 Ferrara, Italy.
Caramori
Gaetano
G
Vincenzi
Fabrizio
F
Adcock
Ian
I
Casolari
Paolo
P
Leung
Edward
E
Maclennan
Stephen
S
Gessi
Stefania
S
Morello
Silvana
S
Barnes
Peter J
PJ
Ito
Kazuhiro
K
Chung
Kian Fan
KF
Cavallesco
Giorgio
G
Azzena
Gianfranco
G
Papi
Alberto
A
Borea
Pier Andrea
PA
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
D018047:Receptors, Purinergic P1