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Involvement of phosphatidylcholine hydrolysis by phospholipase D in extracellular ATP-induced arachidonic acid release in aortic smooth muscle cells.
- Source :
-
Arteriosclerosis, thrombosis, and vascular biology [Arterioscler Thromb Vasc Biol] 1997 Feb; Vol. 17 (2), pp. 295-9. - Publication Year :
- 1997
-
Abstract
- We investigated the effect of extracellular ATP on phosphatidylcholine-hydrolyzing phospholipase D activity and the role of phospholipase D activation in extracellular ATP-induced arachidonic acid release in cultured rat aortic smooth muscle cells. ATP significantly stimulated the formation of choline in a dose-dependent manner in the range between 0.01 and 0.5 mmol/L. However, ATP had no effect on the formation of phosphocholine. Staurosporine, an inhibitor of protein kinases, did not affect the ATP-induced formation of choline. ATP significantly stimulated arachidonic acid release in a dose-dependent manner in the range between 0.01 and 0.5 mmol/L. DL-Propranolol hydrochloride (propranolol), an inhibitor of phosphatidic acid phosphohydrolase, significantly inhibited the ATP-induced release of arachidonic acid. 1,6-Bis(cyclohexyloximinocarbonylamino)-hexane (RHC-80267), a potent and selective inhibitor of diacylglycerol lipase, reduced ATP-induced arachidonic acid release. Quinacrine, a phospholipase A2 inhibitor, suppressed ATP-induced arachidonic acid release. Both propranolol and RHC-80267 markedly inhibited the ATP-induced synthesis of 6-ketoprostaglandin F1 alpha, a stable metabolite of prostacyclin. These results strongly suggest that extracellular ATP activates phosphatidylcholine-hydrolyzing phospholipase D independently of protein kinase C in aortic smooth muscle cells and that the arachidonic acid release induced by extracellular ATP is mediated, at least in part, through phosphatidylcholine hydrolysis by phospholipase D activation.
- Subjects :
- Animals
Aorta cytology
Cells, Cultured
Choline biosynthesis
Enzyme Inhibitors pharmacology
Hydrolysis
Male
Muscle, Smooth, Vascular cytology
Muscle, Smooth, Vascular drug effects
Rats
Rats, Sprague-Dawley
Staurosporine pharmacology
Adenosine Triphosphate metabolism
Aorta metabolism
Arachidonic Acid metabolism
Extracellular Space metabolism
Muscle, Smooth, Vascular metabolism
Phosphatidylcholines metabolism
Phospholipase D metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1079-5642
- Volume :
- 17
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Arteriosclerosis, thrombosis, and vascular biology
- Publication Type :
- Academic Journal
- Accession number :
- 9081684
- Full Text :
- https://doi.org/10.1161/01.atv.17.2.295