Kiss Z
Hormel Institute, University of Minnesota, Austin 55912.
Biochem Pharmacol. 1994 Apr 29;47(9):1581-6. doi: 10.1016/0006-2952(94)90535-5.
Propranolol and sphingosine exhibit several common biochemical effects, including inhibition of phosphatidic acid phosphohydrolase and protein kinase C (PKC) activities. In NIH 3T3 fibroblasts, sphingosine has also been shown to stimulate phospholipase D (PLD)-mediated hydrolysis of both phosphatidylcholine (PtdCho) and phosphatidylethanolamine (PtdEtn) (Kiss Z and Anderson WB, J Biol Chem 265: 7345-7350, 1990). The present study demonstrates that in [14C]palmitic acid-labeled NIH 3T3 fibroblasts, propranolol (50-100 microM) and sphingosine had similar stimulatory effects on PLD-mediated synthesis of phosphatidylethanol in the presence of ethanol. In [14C]choline- and [14C]-ethanolamine-labeled fibroblasts, both compounds also stimulated the hydrolysis of both [14C]PtdCho and [14C]PtdEtn. However, while sphingosine preferentially stimulated PtdEtn hydrolysis, propranolol had greater effects on PtdCho hydrolysis. At each time point examined (15-45 min), lower concentrations (25-50 microM) of propranolol and 100 nM phorbol 12-myristate 13-acetate (PMA) synergistically enhanced PtdEtn hydrolysis; a higher concentration (100 microM) of propranolol inhibited this PMA effect only when the incubation time was 45 min. On the other hand, propranolol (10-100 microM) had either no effect or it inhibited PMA-induced PtdCho hydrolysis after treatments for 15 or 45 min, respectively. These potentiating and inhibitory actions of propranolol on the hydrolysis of PtdCho and PtdEtn were similarly elicited by sphingosine. The present study identified the PLD system as another common target for the pharmacological actions of sphingosine and propranolol.
普萘洛尔和鞘氨醇表现出几种共同的生化效应，包括抑制磷脂酸磷酸水解酶和蛋白激酶C（PKC）的活性。在NIH 3T3成纤维细胞中，鞘氨醇还被证明能刺激磷脂酶D（PLD）介导的磷脂酰胆碱（PtdCho）和磷脂酰乙醇胺（PtdEtn）的水解（Kiss Z和Anderson WB，《生物化学杂志》265：7345 - 7350，1990）。本研究表明，在[14C]棕榈酸标记的NIH 3T3成纤维细胞中，普萘洛尔（50 - 100微摩尔）和鞘氨醇在有乙醇存在的情况下，对PLD介导的磷脂酰乙醇合成具有相似的刺激作用。在[14C]胆碱和[14C]乙醇胺标记的成纤维细胞中，这两种化合物也刺激了[14C]PtdCho和[14C]PtdEtn的水解。然而，虽然鞘氨醇优先刺激PtdEtn水解，但普萘洛尔对PtdCho水解的作用更大。在每个检测时间点（15 - 45分钟），较低浓度（25 - 50微摩尔）的普萘洛尔和100纳摩尔佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）协同增强PtdEtn水解；仅在孵育时间为45分钟时，较高浓度（100微摩尔）的普萘洛尔才抑制这种PMA效应。另一方面，普萘洛尔（10 - 100微摩尔）在分别处理15分钟或45分钟后，对PMA诱导的PtdCho水解要么没有影响，要么起抑制作用。普萘洛尔对PtdCho和PtdEtn水解的这些增强和抑制作用同样由鞘氨醇引发。本研究确定PLD系统是鞘氨醇和普萘洛尔药理作用的另一个共同靶点。
