Prostacyclin analogs stimulate receptor-mediated cAMP synthesis and ATP release from rabbit and human erythrocytes.
OBJECTIVE
The purpose of this study was to establish that the prostacyclin (PGI(2)) 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 PGI(2) 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 PGI(2) analogs were not due to prostaglandin E(2)(PGE(2)) receptor activation, the effect of PGE(2) 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. PGE(2) 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 PGI(2) and its active analogs, when administered pharmacologically, could produce vasodilation.
Sprague
Randy S
RS
Department of Pharmacological and Physiological Science, Saint Louis University, School of Medicine, St. Louis, Missouri 63104, USA. spraguer@slu.edu
Bowles
Elizabeth A
EA
Hanson
Madelyn S
MS
DuFaux
Eileen A
EA
Sridharan
Meera
M
Adderley
Shaquria
S
Ellsworth
Mary L
ML
Stephenson
Alan H
AH
D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis*; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism*; D006801:Humans; D016285:Iloprost / Q000494:pharmacology*; D011817:Rabbits; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000959:Antihypertensive Agents; C113936:PTGIR protein, human; D044006:Receptors, Epoprostenol; D011982:Receptors, Prostaglandin; D014665:Vasodilator Agents; D000255:Adenosine Triphosphate; D011464:Epoprostenol; D000242:Cyclic AMP; D016285:Iloprost; C427248:treprostinil