Adenosine prevents PMA-induced lung injury via an A2 receptor mechanism

Previous studies indicate that adenosine attenuates phorbol myristate acetate-(PMA) induced canine lung injury, but the mechanism has not been explained. To evaluate adenosine's protective mechanism, isolated and blood-perfused dog lungs were challenged by PMA (50 micrograms) under control conditions and after both pre- and post-treatment with adenosine and pretreatment with 2-chloro-N6-cyclopentyladenosine (CCPA), 2-[p-(2-carboxyethyl)phenethylamino]-5'-N-ethylcarboxamido adenosine (CGS 21680C), 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; PD-116948), or isoproterenol. Injury was assessed by measurement of the capillary filtration coefficient (Kf,c), and pulmonary vascular resistance was measured. PMA increased the Kf,c (0.170 +/- 0.015 to 1.030 +/- 0.167 ml.min-1.cmH2O-1.100 g lung wet wt-1) and the total pulmonary vascular resistance (18.2 +/- 3.8 to 110.2 +/- 60.8 cmH2O.l-1.min.100 g lung wet wt). Pretreatment with adenosine, A2 agonist, A1 antagonist, and isoproterenol blocked the increase in Kf,c indu...