Muraki Katsuhiko, Imaizumi Yuji
Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, Nagoya, Japan.
J Pharmacol Sci. 2003 Jul;92(3):252-8. doi: 10.1254/jphs.92.252.
Palmitoyl-L-carnitine (palcar), which accumulates in ischemic heart, affects cellular functions of vascular endothelium in the ischemic area. The aim of this study was to examine the effects of palcar on intracellular Ca(2+) concentration (Ca(2+)) in vascular endothelial cells in comparison with those of sphingosine-1-phosphate (S1P) and to investigate the underlying mechanisms. Application of palcar at a concentration range between 0.3 and 3 micro M elevated Ca(2+) in huvecs, and its potency was about 30 times lower than that of S1P. When human umbilical vein endothelial cells (huvecs) were treated with 100 ng/ml pertussis toxin (PTX) for 15 h, they failed to respond to palcar or S1P, but did respond to 3 micro M histamine (His), suggesting that the response induced by palcar as well as S1P is mediated by a PTX-sensitive GTP binding protein, Gi. Although the sensitivity to palcar and S1P varied widely among huvecs from individuals, response to 3 micro M palcar in each huvec clearly paralleled that to 0.3 micro M S1P (r = 0.79, P<0.001). On the other hand, pre-treatment of huvecs with palcar abolished subsequent S1P-induced elevation of Ca(2+), but not the His-induced elevation. Our data indicate that palcar has a novel action on huvecs as a potential agonist of receptors for S1P. Effective inhibition of the response to S1P by palcar suggests that palcar affects functions regulated by S1P.
在缺血心脏中蓄积的棕榈酰-L-肉碱（palcar）会影响缺血区域血管内皮细胞的细胞功能。本研究旨在比较palcar与1-磷酸鞘氨醇（S1P）对血管内皮细胞内钙离子浓度（Ca(2+)）的影响，并探究其潜在机制。在0.3至3微摩尔浓度范围内应用palcar可升高人脐静脉内皮细胞（huvecs）中的Ca(2+)，其效力约比S1P低30倍。当人脐静脉内皮细胞（huvecs）用100纳克/毫升百日咳毒素（PTX）处理15小时后，它们对palcar或S1P无反应，但对3微摩尔组胺（His）有反应，这表明palcar以及S1P诱导的反应是由PTX敏感的GTP结合蛋白Gi介导的。尽管来自个体的huvecs对palcar和S1P的敏感性差异很大，但每个huvecs对3微摩尔palcar的反应与对0.3微摩尔S1P的反应明显平行（r = 0.79，P<0.001）。另一方面，用palcar预处理huvecs可消除随后S1P诱导的Ca(2+)升高，但不影响His诱导的升高。我们的数据表明，palcar作为S1P受体的潜在激动剂对huvecs具有新作用。palcar对S1P反应的有效抑制表明palcar会影响由S1P调节的功能。
