Alteration of adenosine receptors in patients with chronic obstructive pulmonary disease
Katia Varani1, Gaetano Caramori, Fabrizio Vincenzi
1Department of Clinical and Experimental Medicine, Pharmacology Unit, Via Fossato di Mortara 17-19, 44100 Ferrara, Italy.
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:
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.
Insights
Adenosine receptors in the lungs show altered affinity and density in chronic obstructive pulmonary disease (COPD) patients. These changes in adenosine receptor function may play a role in COPD development.
Area of Science:
- Pulmonary Medicine
- Pharmacology
Background:
- Chronic obstructive pulmonary disease (COPD) is a leading global cause of mortality.
- Adenosine is a key inflammatory regulator with diverse effects mediated by four distinct receptors.
Purpose of the Study:
- To investigate the expression, affinity, and density of adenosine receptors in the lung parenchyma of smokers with COPD versus smokers without COPD.
- To explore the relationship between adenosine receptor characteristics and lung function in COPD patients.
Main Methods:
- Immunohistochemistry and saturation binding assays were used to analyze adenosine receptors (A(1), A(2A), A(2B), and A(3)) in lung tissue.
- Peripheral lung parenchyma samples were obtained from patients with COPD and control subjects.
Main Results:
- All four adenosine receptors were expressed in lung parenchyma cells.
- A(1), A(2A), and A(3) receptors exhibited decreased affinity and increased density in COPD patients.
- A(2B) receptor density was significantly decreased in COPD patients, while affinity remained unchanged.
- Adenosine receptor affinity and density correlated significantly with the FEV(1)/FVC ratio.
Conclusions:
- This study provides the first evidence of altered adenosine receptor expression, affinity, and density in the lung parenchyma of individuals with COPD.
- The findings suggest a potential role for adenosine receptors in the pathogenesis of COPD.
- Further research into adenosine receptor modulation could offer new therapeutic strategies for COPD.
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