Effects of aspirin and dipyridamole on the degradation of adenosine diphosphate by cultured cells derived from bovine pulmonary artery.
To improve understanding of the mechanisms by which ADP is degraded during passage through the pulmonary vascular bed, we examined cultured endothelial and smooth muscle cells of bovine pulmonmary artery for their abilities to metabolize [8-14C]ADP. ADP is rapidly converted to AMP and then to adenosine, hypoxanthine, and inosine. Inosine is the major metabolite produced by endothelial cells. Radioactivity (5-10%) is accumulated intracellularly primarily as ATP. Medium containing 50 micro M ADP incubated with endothelial cells rapidly loses its ability to aggregate platelets and becomes antiaggregatory under conditions in which prostacyclin is absent. The antiaggregatory activity is probably the result of accumulated adenosine. 10 micro M dipyridamole inhibits cellular uptake of radioactivity by greater than 90%, and inosine in the medium is largely replaced by adenosine. This is accompanied by increased anti-aggregatory activity of conditioned medium, which can be matched by authentic adenosine at the same concentration. 1 mM aspirin had no effect on the metabolism of ADP by endothelial cells. Our results suggest: (a) Metabolism of ADP during passage through the lung is mainly the result of endothelial ADPase. (b) ADP released from aggregating platelets can be converted to the antiaggregatory substance, adenosine. Dipyridamole may exert some of its antithrombotic actions by preventing the intracellular uptake of adenosine, thereby increasing its concentration near the site of thrombus formation. (c) The ability of the vessel wall to degrade ADP should not be compromised by the use of aspirin as an antithrombotic drug. (d) Endothelium may retain some of its antithrombogenicity when prostacyclin generation is impaired.
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D001241:Aspirin / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D004176:Dipyridamole / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism*
D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D004176:Dipyridamole; D001241:Aspirin