Prostacyclin Analogs Stimulate Receptor-Mediated cAMP Synthesis and ATP Release from Rabbit and Human Erythrocytes

Abstract

Objectives: The purpose of this study was to establish that the prostacyclin (PGI₂) receptor (IP receptor) is present on rabbit and human erythrocytes and that its activation stimulates cyclic adenosine monophosphate (cAMP) synthesis and adenosine triphosphate (ATP) release.

Methods: The effect of incubation of erythrocytes with the active PGI₂ analogs, iloprost or UT-15C, on cAMP levels and ATP release was determined in the absence and presence of the IP receptor antagonist, CAY10441. Western analysis was used to determine the presence of the IP receptor on isolated membranes. To establish that effects of PGI₂ analogs were not due to prostaglandin E₂(PGE₂) receptor activation, the effect of PGE₂ on cAMP levels and ATP release was determined.

Results: Rabbit and human erythrocytes possess IP receptors. Iloprost and UT-15C stimulated increases in cAMP and ATP release that were prevented by the IP receptor antagonist, CAY10441. PGE₂ did not stimulate cAMP accumulation or ATP release and did not inhibit iloprost-induced increases in cAMP.

Conclusions: This study establishes that the IP receptor is present on rabbit and human erythrocytes and that its activation results in increases in cAMP and ATP release. These results suggest a novel mechanism by which PGI₂ and its active analogs, when administered pharmacologically, could produce vasodilation.

Key words:

• red blood cell
• adenylyl cyclase
• adenosine triphosphate
• iloprost
• UT-15C

ACKNOWLEDGMENTS

The authors thank United Therapeutics Corp. for the gift of UT-15C and also J.L. Sprague for inspiration.

This work was supported by National Institutes of Health (NIH) grants HL64180 and HL-89094 as well as American Diabetes Association grant R-133 (R.S.S.). Individual support was provided by NIH training grant 5T32 GM008306-17 (M.S.H.).