Effect of chlorpromazine on rat arterial lipid synthesis, in vitro.
The effect of chlorpromazine, a major tranquilizer, on arterial lipid metabolism was studied in vitro in rat aortas incubated with [14C]acetate and [14C]mevalonate as lipid precursors. Chlorpromazine at a level of 0.25 mM in the incubation medium significantly reduced the incorporation of [14C]acetate into free fatty acids (p less than 0.01) and total phospholipids (p less than 0.001) but not triglycerides. Chlorpromazine also altered the pattern of arterial phospholipids synthesized from [14C]acetate by significantly increasing the relative proportion of phosphatidylinositol plus phosphatidylserine (p less than 0.02) and reducing the relative proportion of sphingomyelin (p less than 0.001). [14C] Acetate incorporation into the combined fractions of steryl esters plus hydrocarbons and sterols plus diglycerides was also significantly reduced (p less than 0.001) by 0.25 mM chlorpromazine. Studies with [14C]mevalonate showed that chlorpromazine is also an inhibitor of sterol biosynthesis in arterial tissues as evidenced by 35-40% reductions (p less than 0.05) in the formation of 14C-labeled squalene and C27 sterols.
D000085:Acetates / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism*; D002250:Carbon Radioisotopes; D002746:Chlorpromazine / Q000494:pharmacology*; D005230:Fatty Acids, Nonesterified / Q000096:biosynthesis; D005989:Glycerides / Q000096:biosynthesis; D008055:Lipids / Q000096:biosynthesis*; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism; D010743:Phospholipids / Q000096:biosynthesis; D051381:Rats; D013261:Sterols / Q000096:biosynthesis
D000085:Acetates; D002250:Carbon Radioisotopes; D005230:Fatty Acids, Nonesterified; D005989:Glycerides; D008055:Lipids; D010743:Phospholipids; D013261:Sterols; D008798:Mevalonic Acid; D002746:Chlorpromazine