Use of Cultured Cells to Study the Relationship Between Arachidonic Acid and Endothelium-Derived Relaxing Factor

We have used mixedand co-cultures of endothelial and vascular smooth muscle cells to investigate the role of phospholipase activation and arachidonic acid metabolites in the production of endothelium-derived relaxing factor (EDRF). Inhibition of phospholipase A2with para-bromophenacyl bromide, dexam...

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Bibliographic Details
Published in:The American journal of the medical sciences 1988-04, Vol.295 (4), p.287-292
Main Authors: Johns, Roger A., Izzo, Nicholas J., Milner, Peter J., Loeb, Alex L., Peach, Michael J.
Format: Article
Language:English
Subjects:
Acetophenones - pharmacology
Animals
Arachidonic Acid
Arachidonic Acids - metabolism
Biological Products - biosynthesis
Bradykinin - pharmacology
Cell Culture
Cells, Cultured
Cyclic GMP - biosynthesis
Cyclic Guanosine 3’-5’ Monophosphate (Cyclic GMP)
Dexamethasone
Endothelium, Vascular - metabolism
Endothelium-Derived Relaxing Factor (EDRF)
Enzyme Activation
Inositol 1,4,5 Trisphosphate
Melitten - pharmacology
Muscle, Smooth, Vascular - metabolism
Nitric Oxide
Nitroprusside - pharmacology
Para-bromophenacyl Bromide (PBPB)
Phospholipase
Phospholipases - metabolism
Quinacrine
Vascular Smooth Muscle Cells
Vasodilation
Vasodilator Agents - biosynthesis
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Summary:We have used mixedand co-cultures of endothelial and vascular smooth muscle cells to investigate the role of phospholipase activation and arachidonic acid metabolites in the production of endothelium-derived relaxing factor (EDRF). Inhibition of phospholipase A2with para-bromophenacyl bromide, dexamethasone or quinacrine, alone or in combination, blocked arachidonate release by 50%-60% but had no effect on EDRF production as assessed by cyclic GMP accumulation in mixedor co-cultures of endothelial and vascular smooth muscle cells. Inhibition of the phospholipase C-diacylglycerol (DAG) lipase pathway of arachidonate release by the DAG lipase inhibitor RHC-80267 also caused partial inhibition of arachidonate release and had no effect on EDRF. When both phospholipase A2 and phospholipase C pathways for arachidonate mobilization were inhibited (dexamethasone + RHC 80267), arachidonate release was totally inhibited while EDRF release remained intact. We conclude that neither phospholipase activation nor arachidonate mobilization is required for EDRF release from cultured bovine endothelial cells.
ISSN:0002-9629
1538-2990
DOI:10.1097/00000441-198804000-00012