The metabolism of CDP-diacylglycerol and phosphatidylinositol in the microsomal fraction of rat liver. Effects of chlorpromazine, magnesium and manganese.
1. The metabolism of CDPdiacylglycerol and phosphatidylinositol was measured using substrates bound to the microsomal membranes of rat liver. 2. Chlorpromazine inhibited the degradation of [14C]CDPdiacylglycerol and the concomitant inositol-independent release of 14C in water-soluble products in the presence of various concentrations of Mg2+ and Mn2+. 3. The activity of CDPdiacylglycerol inositol phosphatidyltransferase was measured by determining the rate of incorporation of [3H]inositol into phosphatidylinositol, and by the inositol-dependent release of water-soluble 14C from [14C]CDPdiacylglycerol. Both of these parameters were inhibited by chlorpromazine in incubations that contained rate-limiting concentrations of Mg2+. However, chlorpromazine stimulated the reaction when 20 mM Mg2+, 0.5 mM Mn2+, 2 mM Mn2+ or 20 mM Mn2+ was added to the incubations. 4. Low concentrations of chlorpromazine increased an inositol-exchange reaction in the presence of 0.5 mM Mn2+ whereas higher concentrations of chlorpromazine inhibited. Chlorpromazine had relatively less effect on the inositol-exchange reaction at higher concentrations of Mn2+. 5. The action of chlorpromazine in decreasing the breakdown of CDPdiacylglycerol and in stimulating its conversion to phosphatidylinositol could explain part of the mechanism by which this compound and other amphiphilic cations increase the synthesis of acidic phospholipids.
D000818:Animals; D002746:Chlorpromazine / Q000494:pharmacology*; D002855:Chromatography, Thin Layer; D003567:Cytidine Diphosphate Diglycerides / Q000378:metabolism*; D066298:In Vitro Techniques; D007294:Inositol / Q000378:metabolism; D008274:Magnesium / Q000494:pharmacology*; D008345:Manganese / Q000494:pharmacology*; D008563:Membrane Lipids / Q000032:analysis; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009702:Nucleoside Diphosphate Sugars / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D051381:Rats
D003567:Cytidine Diphosphate Diglycerides; D008563:Membrane Lipids; D009702:Nucleoside Diphosphate Sugars; D010716:Phosphatidylinositols; D008345:Manganese; D007294:Inositol; D008274:Magnesium; D002746:Chlorpromazine