Involvement of phosphatidylcholine hydrolysis by phospholipase D in extracellular ATP-induced arachidonic acid release in aortic smooth muscle cells

Junji Shinoda, Atsushi Suzuki, Yutaka Oiso, Osamu Kozawa

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 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.

Original languageEnglish
Pages (from-to)295-299
Number of pages5
JournalArteriosclerosis, thrombosis, and vascular biology
Volume17
Issue number2
DOIs
Publication statusPublished - 01-01-1997
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

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