Prostanoid signal integration and cross talk
Prostanoid signal integration and cross talk
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DOI：
10.1159/000057318
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发表时间：
2002-01-01
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影响因子：
--
通讯作者：
Jones, RL
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文献类型：
--
作者：
Wise, H;Wong, YH;Jones, RL
产生前列腺素的酶机制和负责检测其存在的受体广泛分布在体内。一对前列腺素，前列环素和血栓素 A(2)，在控制血流动力学和止血方面特别重要。前列环素通过作为生理拮抗剂实现其抗血小板作用，但对血栓素 A(2) 介导的血小板活化表现出一定的选择性，这可能是由于血栓素 A(2) 受体无法直接与 G 偶联；蛋白质，并且因为血小板衍生的内过氧化物可以作为内皮细胞中前列环素合成的底物。在低浓度下，前列腺素E-2可通过作用于前列腺素E-2受体的EP3亚型与血栓素A(2)产生协同作用，从而与前列环素的保护功能相反。相反，高浓度的前列腺素 E-2 作用于前列环素受体，也可能作用于前列腺素 D-2 受体，以关闭血小板活化。血管系统中前列腺素信号传导的整合同样复杂，并且由于前列腺素受体在不同血管床中的区域分布以及激动剂和拮抗剂的选择性差，数据的解释变得更加复杂。版权所有 (C) 2002 S. Karger AG，巴塞尔
The enzymatic machinery for the production of prostanoids and the receptors responsible for detecting their presence are widely distributed in the body. One pair of prostanoids, prostacyclin and thromboxane A(2), are particularly important in the control of haemodynamics and haemostasis. Prostacyclin achieves its antiplatelet effect by acting as a physiological antagonist, but displays some selectivity towards thromboxane A(2)-mediated platelet activation, possibly by virtue of the inability of thromboxane A(2) receptors to couple directly to G; proteins, and because platelet-derived endoperoxides can act as substrates for prostacyclin synthesis in endothelial cells. At low concentrations, prostaglandin E-2 can synergize with thromboxane A(2) by acting on the EP3 subtype of prostaglandin E-2 receptor, resulting in opposition to the protective function of prostacyclin. In contrast, high concentrations of prostaglandin E-2 act on the prostacyclin receptor, and possibly the prostaglandin D-2 receptor, to turn off platelet activation. Integration of prostanoid signalling in the vascular system is similarly complex, and interpretation of data is further complicated by the regional distribution of prostanoid receptors in different vascular beds, and the poor selectivity of agonists and antagonists. Copyright (C) 2002 S. Karger AG, Basel