Modulation of endothelial permeability by 1-O-alkylglycerols.
Regulation of endothelial barrier function often occurs through signalling involving phospholipase C activation which produces diacylglycerol (DAG), a lipidic second messenger activator of protein kinase C (PKC). Therefore, modification of lipidic composition of endothelial cell membranes might modify DAG production and, as a result, alter regulation of endothelial permeability. We investigated the in vitro effects of natural 1-O-alkylglycerols on porcine aortic endothelial cell permeability to dye-labelled albumin. [3H]-1-O-alkylglycerols (10 microm) were substantially incorporated into phosphatidylcholine (6.6%) and phosphatidylethanolamine (4.4%). Stimulation of endothelial cell monolayer with phorbol-myristate-acetate or with the calcium ionophore A23187 resulted in a raise in permeability to albumin. Pre-treatment with 1-O-alkylglycerols (10 microm, 24 h) had no effect on basal albumin permeability but totally inhibited the effect of phorbol-myristate-acetate, and brought the permeability of A23187-stimulated endothelial cell monolayers below control. After incubation of cells with [3H]-1-O-alkylglycerols (10 microm, 24 h), we detected the production of the analogue of DAG, and PKC inhibitor, [3H]-1-O-alkyl-2-acyl-glycerol, in resting cells. This production was increased by 58% under A23187 stimulation while phorbol-myristate-acetate had no effect. Our data demonstrate that natural 1-O-alkylglycerols modify endothelial permeability, and suggest that this effect could be mediated through alteration of lipidic signalling.
Marigny
K
K
Laboratoire de Pharmacodynamie et Pharmacologie Moléculaire, Université de Rennes I, Rennes Cedex, France.
Pedrono
F
F
Martin-Chouly
C A E
CA
Youmine
H
H
Saiag
B
B
Legrand
A B
AB
D000418:Albumins / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000166:cytology; D000001:Calcimycin / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects* / Q000502:physiology; D002478:Cells, Cultured; D004396:Coloring Agents / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D005990:Glycerol / Q000031:analogs & derivatives* / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D000418:Albumins; D004396:Coloring Agents; D004075:Diglycerides; D010743:Phospholipids; D013778:Tetrazolium Salts; D013844:Thiazoles; D000001:Calcimycin; D011493:Protein Kinase C; C022616:thiazolyl blue; D013755:Tetradecanoylphorbol Acetate; D005990:Glycerol