Figure 3. Laropiprant antagonizes the increased platelet aggregation by TP and EP3 receptor activation.

In (A), aggregation was induced by U46619 (300 nmol/L) which was concentration-dependently inhibited by laropiprant (n = 4). In B–G, ADP concentrations (1.25–10 μmol/L) were adjusted to give 30–50% of maximal aggregation. (B) The inhibiton of ADP-induced aggregation by the EP4 agonist CAY10598 (300 nmol/L) and the IP agonist iloprost (3 nmol/L) was not affected by laropiprant (10 nmol/L, (n = 7)). (C) The EP3 agonist sulprostone concentration dependently amplified ADP-induced aggregation (n = 4–6). (D) The effect of sulprostone (300 nmol/L) was concentration dependently inhibited by laropiprant (n = 4). (E) Pretreatment with acetylsalicylic acid (1 mmol/L) markedly attenuated the pro-aggregatory effect of sulprostone, and in this case, laropiprant was unable to reverse the stimulatory effect of the EP3 agonist. Data were expressed as percent of control response. (F) The TP receptor antagonist SQ29578 (1 µmol/L) inhibited the sulprostone-induced increase in platelet aggregation to the same extend as laropiprant (10 µmol/L). The combination of SQ29578 and laropiprant did not cause further inhibition as compared to laropiprant or SQ29578 alone (n = 4–6) (G) The pro-aggregatory effect of sulprostone was not inhibited by the EP1 receptor antagonist SC51322 (n = 4). Data were expressed as percent of control ADP response and are shown as mean+SEM. *P<0.05 as compared to vehicle and ^#P<0.05 as compared to the respective agonist treatment.