The effects of PGE2 and CL 115,347, an antihypertensive PGE2 analogue, on human blood platelet behaviour and vascular contractility.
The effects of prostaglandin E2 (PGE2) and an antihypertensive PGE2 analogue, CL 115,347 (d,l-15-deoxy-16-hydroxy-16 (alpha/beta)-vinyl prostaglandin E2 methyl ester), were examined on human blood platelet behaviour in platelet-rich plasma (PRP) and in whole blood (WB). The effects on baseline tone of isolated human carotid arterial strips were also examined. PGE2 had a biphasic effect on platelet behaviour, potentiating ADP- and collagen-induced aggregation at low concentrations (10(-8)-10(-6) M) and inhibiting aggregation at higher concentrations (10(-5) M). In contrast, low concentrations of CL 115,347 (10(-9)-10(-5) M) had no effect on platelet aggregation and higher concentrations (10(-4) M) potentiated ADP- and collagen-induced aggregation. The effects of PGE2 and CL 115,347 on adrenaline-induced aggregation were different to those of the other aggregating agents since only inhibition of platelet aggregation was observed. In the presence of PGI2 (10(-9)-10(-8) M) however, PGE2 (10(-8)-10(-6) M) was able to potentiate both ADP- and adrenaline-induced aggregation. Results obtained in WB were similar to those obtained in PRP. Both PGE2 and CL 115,347 contracted isolated human carotid arterial strips in a dose-dependent manner, with PGE2 being approximately 20 times more potent than its synthetic analogue. These results indicate that CL 115,347 is less potent than PGE2 in its effects on human blood platelet behaviour and vascular contractility in vitro.
D000067956:Adenylyl Cyclase Inhibitors; D000959:Antihypertensive Agents / Q000494:pharmacology*; D015232:Dinoprostone / Q000031:analogs & derivatives; D004837:Epinephrine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D010974:Platelet Aggregation / Q000187:drug effects*; D011458:Prostaglandins E / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D000067956:Adenylyl Cyclase Inhibitors; D000959:Antihypertensive Agents; D011458:Prostaglandins E; D011459:Prostaglandins E, Synthetic; D015232:Dinoprostone; C034232:viprostol; D004837:Epinephrine