Activation of Human Blood Platelets Induced by Nocloprost, a Stable Prostaglandin E₂ Derivative

Abstract

Nocloprost, a 9β-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 μmol/l) caused aggregation with a biphasic course at higher concentrations. Aggregation induced by nocloprost (1 μmol/l) corresponded to that induced by adenosine diphosphate (ADP) (5 μmol/l). Activation of platelets by nocloprost was accompanied by formation of thromboxane A₂ and an increase in cytosolic calcium in In do 1-loaded platelets. At 0.1 μmol/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 μmol/l inhibited aggregation induced by 1 μmol/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.