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Activation of A 3 Adenosine Receptor Provides Lung Protection Against Ischemia‐Reperfusion Injury Associated with Reduction in Apoptosis
Author(s) -
Rivo Julia,
Zeira Evelyne,
Galun Eithan,
Matot Idit
Publication year - 2004
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/j.1600-6143.2004.00620.x
Subject(s) - tunel assay , medicine , reperfusion injury , apoptosis , lung , agonist , pharmacology , ischemia , lung transplantation , adenosine a3 receptor , terminal deoxynucleotidyl transferase , adenosine receptor , anesthesia , endocrinology , receptor , biology , biochemistry , immunohistochemistry
Apoptosis has been described in various models of ischemia‐reperfusion (IR) injury, including lung transplantation. A 3 adenosine receptor (AR) has been linked to a variety of apoptotic processes. The effect of A 3 AR activation on lung injury and apoptosis, following IR, has not been reported to date. In a spontaneously breathing cat model, in which the left lower lobe of the lung was isolated and subjected to 2 h of ischemia and 3 h of reperfusion, we tested the effect of IB‐MECA, a selective A 3 AR agonist, on lung apoptosis and injury. Significant increase in the extent of apoptosis was observed following lung reperfusion. IB‐MECA, administered before IR, and before or with reperfusion, markedly (p < 0.01) attenuated indices of injury and apoptosis including the percentage of injured alveoli, wet/dry weight ratio, myeloperoxidase activity, in situ terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick end‐labeling (TUNEL) positive cells, and caspase 3 activity and expression. The protective effects of IB‐MECA were completely blocked by pretreatment with the selective A 3 AR antagonist MRS‐1191. In summary, even when given after the onset of ischemia, the A 3 AR agonist IB‐MECA conferred a powerful protection against reperfusion lung injury, which was associated with decreased apoptosis. This suggests a potentially important role for A 3 AR in lung IR injury.