A novel action of palmitoyl-L-carnitine in human vascular endothelial cells

Abstract

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 Ca2+ concentration ([Ca2+]i) in vascular endothelial cells in comparison with those of sphingosine-1 -phosphate (SIP) 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 SIP. 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 SIP, but did respond to 3 μM histamine (His), suggesting that the response induced by palcar as well as SIP is mediated by a PTX-sensitive GTP binding protein, Gi. Although the sensitivity to palcar and SIP varied widely among huvecs from individuals, response to 3 μM palcar in each huvec clearly paralleled that to 0.3 μM SIP (r = 0.79, P<0.001). On the other hand, pre-treatment of huvecs with palcar abolished subsequent SIP-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 SIP. Effective inhibition of the response to SIP by palcar suggests that palcar affects functions regulated by SIP.