A Novel Action of Palmitoyl-L-carnitine in Human Vascular Endothelial Cells
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概要
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Palmitoyl-<sc>L</sc>-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 Ca2+ concentration ([Ca2+]i) 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 μM elevated [Ca2+]i 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 μM 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 μM palcar in each huvec clearly paralleled that to 0.3 μM S1P (r = 0.79, P<0.001). On the other hand, pre-treatment of huvecs with palcar abolished subsequent S1P-induced elevation of [Ca2+]i, 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.
- 社団法人 日本薬理学会の論文
- 2003-07-01
著者
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IMAIZUMI Yuji
Department of Molecular and Cellular Pharmacology, Graduate School of Pharmaceutical Sciences, Nagoy
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村木 克彦
名古屋市大・院・細胞分子薬効解析
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MURAKI Katsuhiko
Department of Molecular and Cellular Phamacology, Graduate School of Pharmaceutical Sciences, Nagoya
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Muraki Katsuhiko
Department Of Cellular Pharmacology School Of Pharmacy Aichi-gakuin University
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村木 克彦
Department Of Cellular Pharmacology School Of Pharmacy Aichi-gakuin University
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Imaizumi Yuji
Department Of Chemical Pharmacolgy Faculty Of Pharmaceutical Sciences Nagoya City University
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