Inhibition by adenine dinucleotides of ATP-induced prostacyclin release by bovine aortic endothelial cells

Adenine dinucleotides are a group of extracellular modulators involved in maintaining blood vessel tone. We have demonstrated previously that Ap2A and Ap4A induce the synthesis of both nitric oxide (NO) and prostacyclin (PGI2) in bovine aortic endothelial cells (BAEC), whereas Ap3A, Ap5A, and Ap6A do not. In this paper, we report that Ap2A and Ap4A are partial agonists for ATP in terms of Ca2+ mobilization and PGI2 synthesis. The Ap(4)A EC50 values for Ca2+ mobilization and PGI2 synthesis were significantly higher than the corresponding values for ATP, while the Ap4A B(max) values for Ca2+ mobilization and PGI2 synthesis were significantly lower than those for ATP. Ap2A and Ap4A concentration-effect curves for Ca2+ mobilization and PGI2 synthesis demonstrated that Ap2A and Ap4A have antagonistic effects at ATP concentrations that induce responses above the maximal amount of Ca2+ mobilized or PGI2 synthesized by these two dinucleotides. On the other hand, Ap2A and Ap4A have agonistic effects at ATP concentrations that induce PGI2 synthesis below the maximal amount of PGI2 synthesized by these two dinucleotides. We also present evidence that suggests Ap3A, Ap5A, and Ap6A are antagonists for ATP in terms of PGI2 synthesis. All these data are consistent with the adenine dinucleotides being negative modulators for ATP-induced PGI2 synthesis.