Glusa E, Richter M, Amon I
Institute of Pharmacology and Toxicology, Medical Academy, Erfurt, FRG.
Haemostasis. 1993 Jul-Aug;23(4):203-11. doi: 10.1159/000216876.
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.
诺氯前列素是前列腺素E2（PGE2）的9β-氯-16,16-二甲基衍生物，属于用于治疗胃溃疡的胃细胞保护剂。由于已知PGE2的甲基化衍生物具有促聚集作用，因此研究了其对血小板的影响。在富含血小板的枸橼酸盐血浆中，诺氯前列素（>0.1μmol/L）在较高浓度下会引起双相性聚集。诺氯前列素（1μmol/L）诱导的聚集与二磷酸腺苷（ADP）（5μmol/L）诱导的聚集相当。诺氯前列素激活血小板伴随着血栓素A2的形成以及负载吲哚菁绿1的血小板胞质钙的增加。在0.1μmol/L时，它增强了低浓度ADP或肾上腺素诱导的聚集。诺氯前列素对血小板的作用可被伊洛前列素、达曲班和吲哚美辛阻断。作为对照研究的PGE2，在0.1-1.0μmol/L时可抑制1μmol/L诺氯前列素诱导的聚集。作为抗溃疡药物治疗使用所需的诺氯前列素浓度比诱导人血小板聚集的浓度低三个数量级。
