@article{APS7585,
author = {Min-Qiang Chai and Jun-Song Chen and Sheng Zhao and Jian-Guo Song},
title = {Propranolol increases phosphatidic acid level via activation of phospholipase D},
journal = {Acta Pharmacologica Sinica},
volume = {22},
number = {9},
year = {2016},
keywords = {},
abstract = {Aim: To investigate the propranolol-induced phospholipase D (PLD) activity, its contribution to the increase in the level of phosphatidic acid, and the role of protein kinase C (PKC) in this event.
Methods: A combination of [3H]-myristate labeling, transphosphatidylation reaction, lipid extraction, and thin layer chromatography was used to measure the PLD activity. PKC inhibitors and prolonged phorbol-12-myristate-13-acetate (PMA) treatment were used to study the involvement of PKC in propranolol-induced PLD activation. Immunoblotting was used to detect the intracellular levels of PKC.
Results: Treatment of A-549 cells with propranolol in the presence of butanol, resulted in the rapid activation of PLD. Propranolol induced the formation of phosphatidylbutanol (PBut), a unique product of PLD, at the expense of phosphatidic acid (PA) formation. Pretreatment of cells with PKC inhibitors Ro-31-8220, staurosporine, and rottlerin increased the propranolol-induced PLD. Down-regulation of PKC by prolonged treatment of cells with PMA also potentiated the propranolol-induced PLD activity.
Conclusion: Propranolol induces rapid activation of PLD activity, which results in the increase in intracellular level of PA. The data also indicate that propranolol-induced PLD activity could be negatively regulated by PKC.},
issn = {1745-7254}, url = {http://www.chinaphar.com/article/view/7585}
}