Honohan T, Fitzpatrick F A, Booth D G, McGrath J P, Morton D R, Nishizawa E
Prostaglandins. 1980 Jan;19(1):123-36. doi: 10.1016/0090-6980(80)90160-4.
The prostanoid 3-oxa-4,5,6-trinor-3,7-inter-m-phenylene-PGE1-amide (OI-PGE1-amide) has a prolonged duration of oral platelet aggregation inhibitory activity when compared to the parent free acid (OI-PGE1) in the rat. When incubated in rat plasma at 1 microgram/ml for 30 seconds prior to addition of ADP, OI-PGE1-amide inhibits in vitro rat platelet aggregation approximately 50%. OI-PGE1 inhibits at 1 ng/ml. Inhibition of platelet aggregation by plasma incubated with OI-PGE1-amide (1 microgram/ml) increases with time and the rate of this increase differs with species. Incubation of OI-PGE1 in plasma does not result in an increase of platelet inhibitory activity with time. The increase of platelet inhibitory activity was assumed to indicate hydrolysis of OI-PGE1-amide to the more active OI-PGE1. A compound, different from OI-PGE1-amide, was isolated by an ion exchange/silica gel separation sequence from an incubation of OI-PGE1-amide in rat plasma. It had potent platelet aggregation inhibitory activity. This material was shown to be OI-PGE1 by thin-layer chromatography, gas chromatography and mass spectral analysis. Studies with [3H]-OI-PGE1-amide confirmed the formation of OI-PGE1 in plasma incubations. Amide hydrolytic activity was significantly different between species, the rank order being: rat greater than guine pig greater than monkey = human greater than dog. This relationship corresponded with that determined by measuring the increase in platelet inhibitory activity with time in plasma incubations of OI-PGE1-amide reported above. Present data indicate that (a) OI-PGE1-amide is hydrolyzed to the parent acid by plasma enzymes of several species and (b) hydrolytic activity of plasma varies widely between species.
与大鼠体内的母体游离酸（OI-PGE1）相比，前列腺素3-氧杂-4,5,6-三降-3,7-间亚苯基-PGE1-酰胺（OI-PGE1-酰胺）具有更长的口服血小板聚集抑制活性持续时间。在添加二磷酸腺苷（ADP）之前，将OI-PGE1-酰胺在大鼠血浆中以1微克/毫升的浓度孵育30秒，它在体外可抑制大鼠血小板聚集约50%。OI-PGE1在1纳克/毫升时起抑制作用。用OI-PGE1-酰胺（1微克/毫升）孵育的血浆对血小板聚集的抑制作用随时间增加，且这种增加速率因物种而异。将OI-PGE1在血浆中孵育不会导致血小板抑制活性随时间增加。血小板抑制活性的增加被认为表明OI-PGE1-酰胺水解为活性更高的OI-PGE1。通过离子交换/硅胶分离序列，从OI-PGE1-酰胺在大鼠血浆中的孵育物中分离出一种不同于OI-PGE1-酰胺的化合物。它具有强大的血小板聚集抑制活性。通过薄层色谱法、气相色谱法和质谱分析表明该物质为OI-PGE1。用[3H]-OI-PGE1-酰胺进行的研究证实了在血浆孵育中形成了OI-PGE1。酰胺水解活性在不同物种之间存在显著差异，顺序为：大鼠＞豚鼠＞猴 = 人＞狗。这种关系与通过测量上述OI-PGE1-酰胺在血浆孵育中血小板抑制活性随时间的增加所确定的关系一致。目前的数据表明：（a）OI-PGE1-酰胺被几种物种的血浆酶水解为母体酸；（b）血浆的水解活性在不同物种之间差异很大。
