Fukunaga M, Yura T, Badr K F
Department of Medicine, Emory University, Atlanta, Georgia, USA.
J Cardiovasc Pharmacol. 1995;26 Suppl 3:S51-2.
8-Epi-prostaglandin F2 alpha (8-epi-PGF2 alpha) is an F2-isoprostane produced in vivo by a cyclooxygenase-independent, free radical-catalyzed lipid peroxidation mechanism. It exhibits renal vasoconstrictor effects by binding to a receptor related to, but distinct from, that of thromboxane A2 (TxA2). In cultured bovine aortic endothelial cells (BAECs), competitive binding assays using [3H]-8-epi-PGF2 alpha indicated the existence of two distinct binding sites. The Kd values were similar to those of cultured rat aortic smooth-muscle cells, suggesting that the high- and the low-affinity binding sites represent isoprostane and TxA2 receptors, respectively. 8-Epi-PGF2 alpha dose-dependently stimulated endothelin-1 (ET-1) secretion from BAECs. These increases were partially inhibited by a TxA2 receptor antagonist, consistent with the premise that isoprostanes and TxA2 recognize closely related receptors. The presence of specific binding sites for F2-isoprostanes on endothelial cells widens the scope of the possible pathophysiologic significance of these eicosanoids, released during oxidant injury, to include alteration of endothelial cell biology. The release of ET-1 by 8-epi-PGF2 alpha may help to explain the large increases in plasma and urinary concentrations for both ET-1 and 8-epi-PGF2 alpha in patients with hepatorenal syndrome.
8-表-前列腺素F2α（8-epi-PGF2α）是一种在体内通过不依赖环氧化酶的自由基催化脂质过氧化机制产生的F2-异前列腺素。它通过与一种与血栓素A2（TxA2）相关但不同的受体结合，表现出肾血管收缩作用。在培养的牛主动脉内皮细胞（BAECs）中，使用[3H]-8-epi-PGF2α进行的竞争性结合试验表明存在两个不同的结合位点。其解离常数（Kd）值与培养的大鼠主动脉平滑肌细胞相似，这表明高亲和力和低亲和力结合位点分别代表异前列腺素和TxA2受体。8-epi-PGF2α剂量依赖性地刺激BAECs分泌内皮素-1（ET-1）。这些增加部分被TxA2受体拮抗剂抑制，这与异前列腺素和TxA2识别密切相关受体的前提一致。内皮细胞上存在F2-异前列腺素的特异性结合位点，扩大了这些在氧化损伤期间释放的类二十烷酸可能具有的病理生理意义的范围，包括内皮细胞生物学的改变。8-epi-PGF2α释放ET-1可能有助于解释肝肾综合征患者血浆和尿液中ET-1和8-epi-PGF2α浓度的大幅升高。
