Vascular endothelial and smooth muscle cells in culture selectively release adenine nucleotides

Abstract

Endothelial cells in culture can modulate platelet aggregation and vascular tone, in part by producing prostacyclin (PGI₂)^1,2, a powerful vasodilator and inhibitor of platelet aggregation^3,4, but also by their ecto-ADPase activity⁵, which initiates the conversion of pro-aggregating ADP to adenosine, a potent vasodilator⁶ and platelet inhibitor⁷. We have now demonstrated that cultured aortic endothelial cells exposed to trypsin, thrombin or other stimuli can liberate a high proportion of their adenine nucleotides without substantial loss of lactate dehy-drogenase. ADP rapidly accumulates extracellularly, reaching biologically active concentrations before there is further breakdown to adenosine. Whether this selective release of nucleotides is a response to damage, or whether it represents a specific secretory mechanism remains to be resolved. Cultured aortic smooth muscle cells can secrete adenine nucleotides in a similar manner, but extracellular conversion to adenosine occurs much faster.