Prostacyclin analogs stimulate receptor-mediated cAMP synthesis and ATP release from rabbit and human erythrocytes

Randy S. Sprague, Elizabeth Bowles, Madelyn Hanson, Eileen Dufaux, Meera Sridharan, Shaquria Adderley, Mary Ellsworth, Alan Stephenson

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

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 establishesthat 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.

Original languageEnglish
Pages (from-to)461-471
Number of pages11
JournalMicrocirculation
Volume15
Issue number5
DOIs
StatePublished - Jul 2008

Keywords

  • Adenosine triphosphate
  • Adenylyl cyclase
  • Iloprost
  • Red blood cell
  • UT-15C

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