Vascular smooth muscle actions and receptor interactions of 8-iso-prostaglandin E2, an E2-isoprostane.
8-iso-PGE2, an E2-isoprostane, decreased GFR and RPF dose-dependently in rats, but with lesser potency than 8-epi-PGF2 alpha, an F2-isoprostane. This effect was abolished by SQ29,548. 8-iso-PGE2 displaced [3H]SQ29,548 or [125I]BOP binding in aortic smooth muscle cells with the affinity rank order of SQ29,548 > = I-BOP > U46,619 > 8-iso-PGE2 > PGF2 alpha, while it activated phospholipase C with a potency greater than those of I-BOP or U46,619 and lesser than that of 8-epi-PGF2 alpha. We concluded that 8-iso-PGE2 is a renal vasoconstrictor linked to phosphoinositide metabolism. Its vascular smooth muscle contractile actions are likely mediated through activation of putative thromboxane A2 receptor-like "isoprostane receptors."
Department of Medicine, Emory University, Atlanta, Georgia.
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Fukunaga
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Takahashi
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KF
Badr
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects*; D001643:Bridged Bicyclo Compounds / Q000378:metabolism; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002478:Cells, Cultured; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006834:Hydrazines / Q000378:metabolism; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007536:Isomerism; D028421:Isoprostanes; D007668:Kidney / Q000098:blood supply*; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D010740:Phospholipases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011982:Receptors, Prostaglandin / Q000187:drug effects / Q000378:metabolism*; D018078:Receptors, Prostaglandin E; D017482:Receptors, Thromboxane / Q000037:antagonists & inhibitors; D012039:Regional Blood Flow / Q000187:drug effects
D001643:Bridged Bicyclo Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D028421:Isoprostanes; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D017482:Receptors, Thromboxane; C061750:7-(3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo(2.2.1)heptan-2-yl)-5-heptenoic acid; D015544:Inositol 1,4,5-Trisphosphate; C045749:SQ 29548; D010740:Phospholipases; D015232:Dinoprostone; C011987:8-isoprostaglandin E2