Effects of chlorpromazine on the rate of synthesis of various glycerolipids from [3H]glucose in the human primordial placenta.
The in vitro effect of chlorpromazine (CPZ) on the biosynthesis of various neutral and phospholipids of the 8-10 week old human placenta from [3H]glucose has been studied. Time course (with 0.5 mM CPZ) and dose-response (with 0.1-1.0 mM CPZ) experiments were performed. In order to investigate the significance of the cationic nature of CPZ, the effects were compared with those of 0.05% (v/v) Triton X-100, a nonionic amphiphile, and with the effects of the combined treatments with CPZ and Triton. The results provide evidence that (I) CPZ and Triton stimulate the formation of phosphatidic acid (PA) from glucose, (II) CPZ but not Triton inhibits the activity of phosphatidic phosphohydrolase (PPH), (III) both compounds inhibit the activity of diacylglycerol (DAG)-acyltransferase with an attendant rise of the levels of DAG and phosphatidylcholine (PC), (IV) the combined treatment decreases PC formation presumably due to inhibition of citidylyl transferase activity, (V) CPZ treatment leads to accumulation of labelled phosphatidylinositol (PI) irrespective of the presence or absence of Triton, and (VI) CPZ cannot promote the formation of PI from PA accumulating in response to Triton. The cationic nature of CPZ seems to play specific roles in the inhibition of PPH activity and in the activation of phosphatidyltransferase, both of which direct intermediates toward PI. On the other hand, the amphipathic nature of CPZ and Triton appears sufficient to account for the inhibited DAG-acyltransferase and citidylyl transferase activities.
Gimes
G
G
2nd Department of Obstetrics and Gynecology, Semmelweis Medical University, Budapest, Hungary.
Tóth
M
M
D002746:Chlorpromazine / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D004075:Diglycerides / Q000096:biosynthesis; D005260:Female; D005947:Glucose / Q000378:metabolism*; D005989:Glycerides / Q000096:biosynthesis*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D050356:Lipid Metabolism; D017830:Octoxynol; D010712:Phosphatidic Acids / Q000096:biosynthesis; D010716:Phosphatidylinositols / Q000096:biosynthesis; D010743:Phospholipids / Q000096:biosynthesis; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D014280:Triglycerides / Q000096:biosynthesis
C011439:1,2-diacylglycerol; D004075:Diglycerides; D005989:Glycerides; D010712:Phosphatidic Acids; D010716:Phosphatidylinositols; D010743:Phospholipids; D014280:Triglycerides; D017830:Octoxynol; D005947:Glucose; D002746:Chlorpromazine