Involvement of phospholipase D activation in endothelin-1-induced release of arachidonic acid in osteoblast-like cells

✍ Scribed by Osamu Kozawa; Atsushi Suzuki; Junji Shinoda; Nobuaki Ozaki; Yutaka Oiso; Toshihiko Uematsu

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 108 KB
• Volume: 64
• Category: Article
• ISSN: 0730-2312
• DOI: 10.1002/(sici)1097-4644(19970301)64:3<376::aid-jcb4>3.0.co;2-s

✦ Synopsis

In a previous study, we have shown that endothelin-1 (ET-1) activates phospholipase D independently from protein kinase C in osteoblast-like MC3T3-E1 cells. It is well recognized that phosphatidylycholine hydrolysis by phospholipase D generates phosphatidic acid, which can be further degraded by phosphatidic acid phosphohydrolase to diacylglycerol. In the present study, we investigated the role of phospholipase D activation in ET-1-induced arachidonic acid release and prostaglandin E 2 (PGE 2 ) synthesis in osteoblast-like MC3T3-E1 cells. ET-1 stimulated arachidonic acid release dose-dependently in the range between 0.1 nM and 0.1 µM. Propranolol, an inhibitor of phosphatidic acid phosphohydrolase, significantly inhibited the ET-1-induced arachidonic acid release in a dosedependent manner as well as the ET-1-induced diacylglycerol formation. 1,6-bis-(cyclohexyloxyminocarbonylamino)hexane (RHC-80267), an inhibitor of diacylglycerol lipase, significantly suppressed the ET-1-induced arachidonic acid release. The pretreatment with propranolol and RHC-80267 also inhibited the ET-1-induced PGE 2 synthesis. These results strongly suggest that phosphatidylcholine hydrolysis by phospholipase D is involved in the arachidonic acid release induced by ET-1 in osteoblast-like cells.