PROSTAGLANDIN ENDOPEROXIDES - NEW CONCEPT CONCERNING MODE OF ACTION AND RELEASE OF PROSTAGLANDINS .6.
PROSTAGLANDIN ENDOPEROXIDES - NEW CONCEPT CONCERNING MODE OF ACTION AND RELEASE OF PROSTAGLANDINS .6.
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DOI：
10.1073/pnas.71.10.3824
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发表时间：
1974-01-01
影响因子：
11.1
通讯作者：
SAMUELSSON, B
中科院分区：
文献类型：
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作者：
HAMBERG, M;SVENSSON, J;SAMUELSSON, B
建立了定量测定人血小板中花生四烯酸三种主要代谢产物的方法，12 L-羟基-5，8，10，14-二十碳四烯酸（HETE）、12 L-羟基-5，8，10-十七碳三烯酸（HHT）和8-（1-羟基-3-氧代丙基）-9，12 L-二羟基-5，10-十七碳二烯酸（PHD）。凝血酶引起的洗涤血小板聚集伴随着1163-2175 ng/ml HETE、1129-2430 ng/ml HHT和998-2299 ng/ml PHD的释放。由其代谢物（HHT和PHD）的量的总和计算产生的PGG 2（前列腺素G2）的量为2477-5480 ng/ml。相比之下，释放的PGE 2（前列腺素E2）和PGF 2 α（前列腺素F2α）的量大约低两个数量级。因此，在这个系统中，黑素通过内过氧化物发挥其生物学作用，内过氧化物几乎完全代谢为非前列腺酸结构，仅在很小程度上代谢为经典的黑素。这为我们先前的提议提供了额外的证据[Hamberg，M.，Svensson，J.，Wakabayashi，T. & Samuelsson，B.等人（1974）Proc. Sci. USA 71，345-349]，阿司匹林的抗聚集作用是通过抑制PGG 2的形成。
Methods were developed for quantitative determination of the three major metabolites of arachidonic acid in human platelets, i.e., 12L-hydroxy-5,8,10,14-eicosatetraenoic acid (HETE), 12L-hydroxy-5,8,10-heptadecatrienoic acid (HHT) and 8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid (PHD). Aggregation of washed platelets by thrombin was accompanied by release of 1163-2175 ng/ml of HETE, 1129-2430 ng/ml of HHT, and 998-2299 ng/ml of PHD. The amount of PGG2(prostaglandin G2) produced as calculated from the sum of the amounts of its metabolites (HHT and PHD) was 2477-5480 ng/ml. In contrast, the amounts of PGE2(prostaglandin E2) and PGF2α(prostaglandin F2α) released were approximately two orders of magnitude lower. In this system, the prostaglandins thus exert their biological action through the endoperoxides, which are almost exclusively metabolized to nonprostanoate structures and only to a small extent to the classical prostaglandins.Platelets from subjects given aspirin produced less than 5% of the above mentioned amounts of HHT and PHD, whereas the production of HETE was stimulated about 3-fold. This provides additional evidence for our earlier proposal [Hamberg, M., Svensson, J., Wakabayashi, T. & Samuelsson, B. (1974)Proc. Nat. Acad. Sci. USA71, 345-349] that the anti-aggregating effect of aspirin is through inhibition of PGG2formation.