THE F2-ISOPROSTANE, 8-EPI-PROSTAGLANDIN-F2-ALPHA, A POTENT AGONIST OF THE VASCULAR THROMBOXANE ENDOPEROXIDE RECEPTOR, IS A PLATELET THROMBOXANE ENDOPEROXIDE RECEPTOR ANTAGONIST
THE F2-ISOPROSTANE, 8-EPI-PROSTAGLANDIN-F2-ALPHA, A POTENT AGONIST OF THE VASCULAR THROMBOXANE ENDOPEROXIDE RECEPTOR, IS A PLATELET THROMBOXANE ENDOPEROXIDE RECEPTOR ANTAGONIST
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DOI：
10.1016/0090-6980(92)90077-7
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发表时间：
1992-08-01
期刊：
影响因子：
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通讯作者：
ROBERTS, LJ
中科院分区：
文献类型：
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作者：
MORROW, JD;MINTON, TA;ROBERTS, LJ
F2-异前列烷是最近发现的一系列前列腺素（PG）F2样化合物，其通过花生四烯酸的非酶自由基催化过氧化在人体内产生。可以通过这种机制大量产生的化合物之一是8-epi-PGF 2-α。8-epi-PGF 2-α在大鼠中是一种有效的血管收缩剂，该作用已被证明是通过与血管血栓烷（TxA 2）/内过氧化物（PGH 2）受体相互作用介导的。为了进一步了解这种前列腺素类与TxA 2/PGH 2受体相互作用的生物学特性，我们研究了其对人类和大鼠血小板的影响。 在10（-6）M和10（-5）M浓度下，8-epi-PGF 2-alpha仅诱导人血小板形状变化，在更高浓度（10（-4）M）下诱导可逆但不可逆的聚集。吲哚美辛不影响形态变化和可逆聚集，但TxA 2/PGH 2受体拮抗剂SQ 29548可抑制形态变化和可逆聚集。相反，8-epi-PGF 2-alpha抑制由TxA 2/PGH 2受体激动剂U46619（10（-6）M）和IBOP（3.3 × 10（-7）M）诱导的血小板聚集，IC 50分别为1.6 × 10（-6）M和1.8 × 10（-6）M。8-epi-PGF 2-α也抑制花生四烯酸诱导的血小板聚集。类似地，在大鼠血小板中，单独的8-epi-PGF 2-α仅诱导适度的可逆性聚集，但完全抑制U46619诱导的聚集。
F2-isoprostanes are a recently discovered series of prostaglandin (PG)F2-like compounds that are produced in vivo in humans by nonenzymatic free radical catalyzed peroxidation of arachidonic acid. One of the compounds that can be produced in abundance by this mechanism is 8-epi-PGF2-alpha. 8-epi-PGF2-alpha is a potent vasoconstrictor in the rat, an effect that has been shown to be mediated via interaction with vascular thromboxane (TxA2)/ endoperoxide (PGH2) receptors. In an effort to further understand the biological properties of this prostanoid in relation to its ability to interact with TxA2/PGH2 receptors, we examined its effects on human and rat platelets. At concentrations of 10(-6) M and 10(-5) M, 8-epi-PGF2-alpha induced only a shape change in human platelets and at higher concentrations (10(-4) M) induced reversible but not irreversible aggregation. Both the shape change and reversible aggregation were unaffected by indomethacin but were inhibited by the TxA2/PGH2 receptor antagonist SQ29548. Conversely, 8-epi-PGF2-alpha inhibited platelet aggregation induced by the TxA2/PGH2 receptor agonists U46619 (10(-6) M) and IBOP (3.3xl0(-7) M) with an IC50 of 1.6 x 10(-6) M and 1.8 x 10(-6) M, respectively. 8-epi-PGF2-alpha also inhibited platelet aggregation induced by arachidonic acid. Similarly, in rat platelets, 8-epi-PGF2-alpha alone induced only modest reversible aggregation but completely inhibited U46619-induced aggregation.