Hamberg M, Svensson J, Samuelsson B
Proc Natl Acad Sci U S A. 1975 Aug;72(8):2994-8. doi: 10.1073/pnas.72.8.2994.
An unstable [t1/2 at 37 degrees = 32 +/- 2 (SD) sec] intermediate, thromboxane A2, was detected in the conversion of prostaglandin G2 into 8-(1-hydroxy-3-oxopropyl)-9,12L-dihydroxy-5,10-heptadecadienoic acid (thromboxane B2) in platelets. The intermediate was trapped by addition of methanol, ethanol, or sodium azide to suspensions of washed human platelets incubated for 30 sec with arachidonic acid or prostaglandin G2. The structures of the resulting derivatives demonstrated that the intermediate possessed an oxane ring as in thromboxane B2 but lacked its hemiacetal hydroxyl group. Additional experiments using 18O2 or [2H8]arachidonic acid in the formation of thromboxane B2 and CH3O2H for the trapping of thromboxane A2, together with information on the t1/2 of the intermediate, indicated the presence of an oxetane structure in thromboxane A2. Incubation of arachidonic acid or prostaglandin G2 with washed platelets led to formation of an unstable factor that induced irreversible platelet aggregation and caused release of [14C]serotonin from platelets that had been incubated with [14C]serotonin. The properties and the mode of formation of this factor indicated that it was identical with thromboxane A2. Furthermore, evidence is presented that the more unstable and major component of rabbit aorta contracting substance (RCS) formed in platelets and guinea pig lung is also thromboxane A2.
在血小板中，前列腺素G2转化为8-(1-羟基-3-氧代丙基)-9,12L-二羟基-5,10-十七碳二烯酸（血栓素B2）的过程中，检测到一种不稳定的中间体（37℃时半衰期t1/2 = 32±2（标准差）秒），即血栓素A2。通过向用花生四烯酸或前列腺素G2孵育30秒的洗涤过的人血小板悬液中加入甲醇、乙醇或叠氮化钠来捕获该中间体。所得衍生物的结构表明，该中间体具有与血栓素B2相同的氧杂环戊烷环，但缺少其半缩醛羟基。在血栓素B2形成过程中使用18O2或[2H8]花生四烯酸以及用CH3O2H捕获血栓素A2的其他实验，连同中间体半衰期的信息，表明血栓素A2中存在氧杂环丁烷结构。用花生四烯酸或前列腺素G2孵育洗涤过的血小板会导致形成一种不稳定因子，该因子诱导不可逆的血小板聚集，并使已用[14C]血清素孵育的血小板释放[14C]血清素。该因子的性质和形成方式表明它与血栓素A2相同。此外，有证据表明，在血小板和豚鼠肺中形成的兔主动脉收缩物质（RCS）中更不稳定且主要的成分也是血栓素A2。
