Abstract
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."
MeSH terms
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Animals
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Aorta, Thoracic / drug effects
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Aorta, Thoracic / metabolism
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Aorta, Thoracic / physiology
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Binding, Competitive
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Blood Pressure / drug effects*
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Bridged Bicyclo Compounds / metabolism
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Bridged Bicyclo Compounds, Heterocyclic*
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Cells, Cultured
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Dinoprostone / analogs & derivatives*
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Dinoprostone / pharmacology
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Enzyme Activation
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Fatty Acids, Unsaturated / metabolism
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Glomerular Filtration Rate / drug effects
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Hydrazines / metabolism
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Inositol 1,4,5-Trisphosphate / metabolism
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Isomerism
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Isoprostanes*
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Kidney / blood supply*
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Kinetics
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Male
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Muscle, Smooth, Vascular / drug effects
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Muscle, Smooth, Vascular / metabolism
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Muscle, Smooth, Vascular / physiology*
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Phospholipases / metabolism
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Rats
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Rats, Sprague-Dawley
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Receptors, Prostaglandin / drug effects
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Receptors, Prostaglandin / metabolism*
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Receptors, Prostaglandin E
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Receptors, Thromboxane / antagonists & inhibitors
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Regional Blood Flow / drug effects
Substances
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Bridged Bicyclo Compounds
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Bridged Bicyclo Compounds, Heterocyclic
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Fatty Acids, Unsaturated
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Hydrazines
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Isoprostanes
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Receptors, Prostaglandin
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Receptors, Prostaglandin E
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Receptors, Thromboxane
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7-(3-(3-hydroxy-4-(4'-iodophenoxy)-1-butenyl)-7-oxabicyclo(2.2.1)heptan-2-yl)-5-heptenoic acid
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Inositol 1,4,5-Trisphosphate
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SQ 29548
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Phospholipases
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Dinoprostone
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8-isoprostaglandin E2