Stimulatory effect of 8-Epi-PGF2 alpha, an F2-isoprostane, on endothelin-1 release.
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.
Fukunaga
M
M
Department of Medicine, Emory University, Atlanta, Georgia, USA.
Yura
T
T
Badr
K F
KF
D000818:Animals; D001667:Binding, Competitive; D002417:Cattle; D002478:Cells, Cultured; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D016232:Endothelins / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D016232:Endothelins; D014662:Vasoconstrictor Agents; C075750:8-epi-prostaglandin F2alpha; D015237:Dinoprost