Activation of human blood platelets induced by nocloprost, a stable prostaglandin E2 derivative

Nocloprost, a 9 beta-chloro-16,16-dimethyl derivative of prostaglandin E2 (PGE2), belongs to the gastric cytoprotective agents that are used in the therapy of gastric ulcer. Since methylated derivatives of PGE2 are known to have proaggregatory effects the influence on platelets was studied. In platelet-rich citrated plasma, nocloprost (> 0.1 mumol/l) caused aggregation with a biphasic course at higher concentrations. Aggregation induced by nocloprost (1 mumol/l) corresponded to that induced by adenosine diphosphate (ADP) (5 mumol/l). Activation of platelets by nocloprost was accompanied by formation of thromboxane A2 and an increase in cytosolic calcium in Indo 1-loaded platelets. At 0.1 mumol/l it potentiated aggregation induced by low concentrations of ADP or adrenaline. The effect of nocloprost on platelets was blocked by iloprost, daltroban and indomethacin. PGE2, which was studied for comparison, at 0.1-1.0 mumol/l inhibited aggregation induced by 1 mumol/l nocloprost. The concentrations of nocloprost required for therapeutic use as antiulcer agent were lower by three orders of magnitude than those which induce human platelet aggregation.