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 diacyl-glycerol 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-keto-prostaglandin F(1α), 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.
|Number of pages||5|
|Journal||Arteriosclerosis, thrombosis, and vascular biology|
|Publication status||Published - 1997|
All Science Journal Classification (ASJC) codes
- Cardiology and Cardiovascular Medicine