Effects of the antithrombotic drug suloctidil on low density lipoprotein processing and cholesterol metabolism in cultured human fibroblasts.
Human foetal lung fibroblasts were pretreated for 24 h with the antithrombotic drug, suloctidil (1 to 10 mumol/l), which induced a dose-dependent increase in LDL binding, uptake and degradation. At 10 mumol/l suloctidil, the respective increases in these parameters were 40%, 80% and 50%. The same treatment also resulted in increases of 1.5 to 2-fold in the synthesis of sterols, fatty acids and triacylglycerols from sodium acetate. In contrast, the esterification of cholesterol with oleic acid was specifically decreased by 35% by 24 h pretreatment of fibroblasts with 10 mumol/l suloctidil. A similar decrease of cholesterol esterification was observed in cholesterol-laden fibroblasts. It is suggested that these effects of suloctidil on LDL processing and cholesterol metabolism are related to the amphiphilic characteristics of the drug and to its calcium-blocking properties.
Mazière
C
C
Faculté de Médecine Saint-Antoine, Service de Chimie Biologique, Paris, France.
Mazière
J C
JC
Houtia
N E
NE
Lauga
J
J
Polonovski
J
J
D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D011412:Propanolamines / Q000494:pharmacology*; D011973:Receptors, LDL / Q000187:drug effects / Q000378:metabolism; D013468:Suloctidil / Q000494:pharmacology*
D008077:Lipoproteins, LDL; D011412:Propanolamines; D011973:Receptors, LDL; D002784:Cholesterol; D013468:Suloctidil