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Graier, WF; Hoebel, BG; Frank, S; Kostner, GM.
Intracellular action of epoxyeicosatrienoic acids in endothelial cells
ENDOTHELIUM-DEPENDENT HYPERPOLARIZATIONS. 1999; 69-75.
Web of Science

Leading authors Med Uni Graz: Graier Wolfgang
Co-authors Med Uni Graz: Kostner Gerhard
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Abstract:: Besides their contribution to endothelium-dependent hyperpolarization, the understanding of the physiological function of endothelium-generated epoxyeicosatrienoic acids is limited. In the present work it is intended to verify intracellular properties of these cytochrome P450 epoxygenase-derived metabolites of arachidonic acid in porcine endothelial cells, Evidence is provided that epoxyeicosatrienoic acids contribute to the regulation of intracellular Ca2+ concentration by affecting the driving force for Ca2+ influx through the capacitative Call entry in endothelial cells, which is due to hyperpolarization of the cell membrane. Enzyme induction by dexamethasone/clofibrate increase cytochrome P450 epoxygenase activity, Ca2+/Mn2+ entry and membrane hyperpolarization in response to thapsigargin, a powerful stimulus for cytochrome P450 epoxygenase. Epoxyeicosatrienoic acids stimulated endothelial tyrosine kinase. Arachidonic acid, mimicked the effect of the epoxyeicosatrienoic acids on tyrosine kinase activity at high concentration. Since the effect of arachidonic acid but not that of the epoxyeicosatrienoic acids on tyrosine kinase was prevented by thiopentone sodium (an inhibitor of cytochrome P450 epoxygenase), arachidonic acid probably has to be converted to epoxyeicosatrienoic acids in order to stimulate endothelial tyrosine kinase. These data strongly indicate that epoxyeicosatrienoic acids not only serve as putative endothelium-derived hyperpolarizing factor(s) but also have important intracellular functions in endothelial cells.
Find related publications in this database (Keywords): Ca2+ homeostasis; cytochrome P450 epoxygenase hyperpolarization; tyrosine kinase