Paper
Stimulatory Effect of 8‐Epi-PGF2α, An F2-Isoprostane, on Endothelin‐1 Release
Published 1995 · M. Fukunaga, T. Yura, K. Badr
Journal of Cardiovascular Pharmacology
59
Citations
1
Influential Citations
Abstract
Summary: 8-Epi-prostaglandin F2α (8-epi-PGF2α) 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-PGF2α 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-PGF2α 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-PGF2α may help to explain the large increases in plasma and urinary concentrations for both ET-1 and 8-epi-PGF2α in patients with hepatorenal syndrome.
In Vitro Study8-epi-PGF2 stimulates endothelin-1 secretion from endothelial cells, potentially explaining increased levels in hepatorenal syndrome patients.
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