期刊
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
卷 55, 期 6, 页码 555-559出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FJC.0b013e3181d8bec5
关键词
U73122; phospholipase C; phospholipase D; phosphatidylinositol 4, 5-bisphosphate; rat myocardium
资金
- Deutsche Forschungsgemeinschaft [KU 774/5-1]
The aminosteroid 1-[6-({17 beta-3-methoxyestra-1,3,5(10)-trien-17-yl}amino)hexyl]-1H-pyrrole-2,5-dione (U73122) has been extensively used as a pharmacologic inhibitor of phospholipase C (PLC). The inhibitory effect of U73122 on PLC activity is most likely the result of decreased availability of phosphatidylinositol 4,5-bisphosphate (PIP2), the substrate of the PLC signal transduction pathway, rather than direct inhibition of the enzyme. PIP2 is a phospholipid with pleiotropic cellular functions, including a pivotal role in regulating cardiac phospholipase D (PLD) signal transduction. Here, we hypothesized that U73122 acts as an inhibitor of cardiac PLD activity by interference with PIP2. U73122 concentration-dependently inhibited PLD activity in rat myocardial membranes. The inhibitory effect of U73122 was significantly attenuated when assayed on solubilized PLD activity and was completely restored if solubilized PLD activity was assayed in the presence of PIP2. U73122 had no inhibitory effect on purified PLD indicating that the substance does not interact with PLD directly. These data highlight a mechanism of action of U73122 as an inhibitor of myocardial PLD by interaction with PIP2 as a cofactor for optimal PLD activity. Hence, studies using U73122 as a specific inhibitor of PLC have to take into account that PLD may be involved in some of the effects ascribed to PLC.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据