Acute reversible reduction of PGI2 platelet receptors after iloprost infusion in man

Platelet sensitivity to PGI2 and platelet PGI2 receptors were investigated in eight subjects with peripheral artery disease (stage IV according to Fontaine) treated for 14 consecutive days with six hour iv infusion of Iloprost (Schering, FRG) 2 ng/Kg/min. Platelet studies were performed on the 1st, the 2nd, the 7th and the 14th day of therapy, immediately before infusion (between 8.00 and 9.00 a.m.), at the end and 6 and 18 hours (the following morning) after the end of the infusion. Platelet sensitivity to PGI2 was assessed by determining the PGI2 inhibitory dose 50(ID 50) on platelet aggregation induced by 5 μM ADP. PGI2 platelet receptors were investigated by a direct radioligand binding assay.

PGI2 ID 50 after the infusion was significantly higher than that at baseline(p<0.01) and six hours later the baseline sensitivity was restored. After the six hour Iloprost iv infusion a significant reduction in the number of high affinity PGI2 platelet receptor (HAR) was observed (p<0.005) without any change in their affinity for the ligand. Six hours after the end of the infusion the number of the HAR was still significantly reduced (p<0.05). The following morning the receptor number of HAR was restored. The baseline values of PGI2 HAR, when reassessed after seven and fourteen days of treatment, were not significantly different from those recorded on the first day of therapy. These data indicate that the reduction of platelet PGI2 sensitivity following short-term Iloprost infusion is rapidly reversible and is related to a contemporary down-regulation of PGI2 platelet receptors. However the observed decrease of the number of PGI2 receptors, in the absence of any changes in affinity for the ligand, seems unable to explain the reduced biological effects so that the existence of other post-binding alterations could be postulated.