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 induced by PMA. These agents also slightly attenuated the resistance increase induced by PMA, with the exception of the A1 antagonist, which completely prevented the resistance increase (24.3 +/- 7.8 to 23.4 +/- 8.1 cmH2O.l-1.min.100 g lung wet wt). The A1 agonist also slightly attenuated the increase in Kf,c (0.174 +/- 0.022 to 0.486 +/- 0.128 ml.min-1.cmH2O-1.100 g lung wet wt-1) and did not affect the resistance increase. Posttreatment with adenosine did not significantly affect the changes induced by PMA. These data show that PMA-induced increases in capillary permeability in the isolated blood-perfused dog lung can be blocked by pretreatment with adenosine, which binds the adenosine A2 receptors.
Adkins
W K
WK
Department of Physiology, College of Medicine, University of South Alabama, Mobile 36688.
Barnard
J W
JW
Moore
T M
TM
Allison
R C
RC
Prasad
V R
VR
Taylor
A E
AE
D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002199:Capillary Permeability / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis; D004285:Dogs; D004727:Endothelium / Q000166:cytology / Q000502:physiology; D005260:Female; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008171:Lung Diseases / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D058914:Purinergic Antagonists; D011983:Receptors, Purinergic / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*; D014655:Vascular Resistance / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology
D058914:Purinergic Antagonists; D011983:Receptors, Purinergic; D014970:Xanthines; C058394:2-chloro-N(6)cyclopentyladenosine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000242:Cyclic AMP; D000241:Adenosine; D007545:Isoproterenol; D013755:Tetradecanoylphorbol Acetate