ARTERIAL-WALLS ARE PROTECTED AGAINST DEPOSITION OF PLATELET THROMBI BY A SUBSTANCE (PROSTAGLANDIN-X) WHICH THEY MAKE FROM PROSTAGLANDIN ENDOPEROXIDES
ARTERIAL-WALLS ARE PROTECTED AGAINST DEPOSITION OF PLATELET THROMBI BY A SUBSTANCE (PROSTAGLANDIN-X) WHICH THEY MAKE FROM PROSTAGLANDIN ENDOPEROXIDES
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DOI：
10.1016/0090-6980(76)90047-2
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发表时间：
1976-01-01
影响因子：
2.9
通讯作者：
VANE, JR
中科院分区：
文献类型：
--
作者：
GRYGLEWSKI, RJ;BUNTING, S;VANE, JR
前列腺素（PG）内过氧化物（PGG2和PGH2）收缩动脉平滑肌并引起血小板聚集。来自猪主动脉、猪肠系膜动脉、兔主动脉和大鼠胃底的微粒体可将PG内过氧化物酶转化为不稳定产物（PGX），使动脉条带松弛，阻止血小板聚集。来自大鼠胃体、大鼠肝脏、兔肺、兔脾、兔脑、兔肾髓质、公羊精囊和大鼠皮肤匀浆颗粒部分的微粒体将PG内过氧化物转化为PGE-和pgf，而不是转化为pgx样活性。PGX不同于目前已知的前列腺素内过氧化物酶转化的产物，包括PGE2， F2.alpha。D2、血栓素A2及其代谢物。PGX对大鼠基底条、鸡直肠、豚鼠回肠和豚鼠气管的收缩活性低于PGG2和PGH2。PGX不会使大鼠结肠收缩。PGX在水溶液中不稳定，沸水0.25 min或37℃下10 min抗聚集活性消失。C.作为花生四烯酸体外诱导的人血小板聚集抑制剂，PGX的抑制作用是PGE1的30倍。15-羟基花生四烯酸可抑制PGX的酶促生成（IC50 = 0.48 .mu）。g/ml)，自发氧化花生四烯酸(IC50[50%抑制浓度]< 100 .mu。g/ml)和丙基环丙胺（IC50 = 160 μ g/ml）。动脉壁形成阻止血小板聚集的PGX和血小板释放诱导聚集的前列腺素内过氧化物之间的平衡对于控制血管血栓形成至关重要。
Prostaglandin (PG) endoperoxides (PGG2 and PGH2) contract arterial smooth muscle and cause platelet aggregation. Microsomes from pig aorta, pig mesenteric arteries, rabbit aorta and rat stomach fundus enzymically transform PG endoperoxides to an unstable product (PGX) which relaxes arterial strips and prevents platelet aggregation. Microsomes from rat stomach corpus, rat liver, rabbit lungs, rabbit spleen, rabbit brain, rabbit kidney medulla, ram seminal vesicles and particulate fractions of rat skin homogenates transform PG endoperoxides to PGE- and PGF-rather than to PGX-like activity. PGX differs from the products of enzymic transformation of prostaglandin endoperoxides so far identified, including PGE2, F2.alpha., D2, thromboxane A2 and their metabolites. PGX is less active in contracting rat fundic strip, chick rectum, guinea pig ileum and guinea pig trachea than are PGG2 and PGH2. PGX does not contract the rat colon. PGX is unstable in aqueous solution and its anti-aggregating activity disappears within 0.25 min on boiling or within 10 min at 37.degree. C. As an inhibitor of human platelet aggregation induced in vitro by arachidonic acid PGX was 30 times more potent than PGE1. The enzymic formation of PGX is inhibited by 15-hydroperoxy arachidonic acid (IC50 = 0.48 .mu.g/ml), by spontaneously oxidized arachidonic acid (IC50 [50% inhibitory concentration] < 100 .mu.g/ml) and by tranylcypromine (IC50 = 160 .mu.g/ml). A balance between formation by arterial walls of PGX which prevents platelet aggregation and release by blood platelets of prostaglandin endoperoxides which induce aggregation is of the utmost importance for the control of thrombus formation in vessels.