Ney P, Braun M, Szymanski C, Bruch L, Schrör K
Institut für Pharmakologie, Heinrich-Heine-Universität Düsseldorf, Federal Republic of Germany.
Eicosanoids. 1991;4(3):177-84.
The actions of the in vivo metabolite of PGE1, 13,14-dihydro-PGE1 (PGE0), on platelet and neutrophil (PMN) function and vessel tone were studied in vitro. PGE0 inhibited aggregation, ATP release and thromboxane generation by human platelets (IC50 10-100 nmoles/l). The compound also inhibited superoxide anion generation and lysosomal enzyme release from human PMN. PGE0 was equipotent to PGE1 in both systems, while 15-keto-PGE1 was ineffective in platelets but produced some inhibition in PMN. These inhibitory effects of PGE0 and PGE1 were paralleled by concentration-dependent increases in cyclic AMP in platelets and PMN. Both compounds were also potent relaxants of several arterial preparations in the rabbit at comparable concentrations. In general, the vasorelaxing properties of PGE0 were somewhat lower and the contractile effects somewhat stronger in comparison to PGE1. These data demonstrate a significant and concentration-dependent inhibition of receptor-mediated activation of human platelets and PMN by PGE0. The molar potency of the compound is comparable to that of PGE1. Generation of PGE0 from infused PGE1 may contribute to the clinical efficacy of PGE1 in treatment of severe peripheral arterial occlusive disease.
在体外研究了前列腺素E1（PGE1）的体内代谢产物13,14-二氢-PGE1（PGE0）对血小板、中性粒细胞（PMN）功能及血管张力的作用。PGE0可抑制人血小板的聚集、ATP释放及血栓素生成（IC50为10 - 100纳摩尔/升）。该化合物还可抑制人PMN中超氧阴离子的生成及溶酶体酶的释放。在这两个系统中，PGE0与PGE1的效力相当，而15-酮-PGE1对血小板无效，但对PMN有一定抑制作用。PGE0和PGE1的这些抑制作用伴随着血小板和PMN中环状AMP浓度依赖性的增加。在相当浓度下，这两种化合物对兔的几种动脉制剂也是有效的舒张剂。总体而言，与PGE1相比，PGE0的血管舒张特性略低，收缩作用略强。这些数据表明PGE0对人血小板和PMN的受体介导激活具有显著的浓度依赖性抑制作用。该化合物的摩尔效力与PGE1相当。由输注的PGE1生成PGE0可能有助于PGE1治疗严重外周动脉闭塞性疾病的临床疗效。
