Prostacylin(PGI2) analogs stimulate receptor‐mediated increases in cAMP accumulation and ATP release from rabbit and human red blood cells(RBCs)

Abstract

Activation of the G proteins, Gs and Gi, stimulates increases in cAMP and ATP release from rabbit and human RBCs. Previously, we showed that the PGI2 analog, iloprost (ILO), stimulates increases in cAMP and ATP release from rabbit RBCs. Here we show that a structurally dissimilar analog, UT‐15C (UT), also produces concentration‐dependent increases in cAMP (n=4) and a 329±136% increase in ATP release (1 μM, n=9) from these cells. This effect is not limited to rabbit RBCs since ILO stimulated concentration‐dependent increases in cAMP (n=4) and a 328±92% increase in ATP release (1 μM, n=9) from human RBCs as well. To determine if these increases are receptor mediated, RBCs were pretreated with CAY10441 (10 μM), a PGI2 (IP) receptor antagonist. CAY10441 prevented ILO‐ and UT‐induced cAMP accumulation and ATP release. To ensure that responses were not the result of PGE2 (EP) receptor activation, RBCs were incubated with PGE2 (1 μM). PGE2 had no effect on cAMP or ATP release. Finally, using Western analysis, we determined that the IP receptor is present in rabbit and human RBC membranes. These results are consistent with the hypothesis that PGI2 analogs stimulate receptor‐mediated cAMP increases and ATP release from RBCs. This suggests a heretofore unrecognized mechanism by which these agents, when administered pharmacologically, can decrease vascular resistance. Funded by NIH, HL‐64180 and ADA, RA‐133.