Phospholipase A2 inhibitors. Differential inhibition of fatty acid acylation into kidney lipids by mepacrine and p-bromophenacyl bromide.
Mepacrine and p-bromophenacyl bromide, in addition to their inhibitory effect on lipolysis, are also potent inhibitors of fatty acid acylation into renal medullary lipids. Significant qualitative and quantitative differences in the inhibition by the two drugs were seen. p-Bromophenacyl bromide exerted a non-selective effect inhibiting the incorporation of saturated and unsaturated fatty acids into all phospholipid classes and triacylglycerols. In contrast, mepacrine selectively inhibited the incorporation of both saturated and unsaturated acids into phosphatidylcholine, phosphatidylethanolamine and triglycerides, and concurrently markedly enhanced their incorporation into phosphatidylinositol. Quantitative analysis of these mepacrine effects, together with the known inhibitory effects of this compound on phospholipase A2 and phosphatidylinositol-specific phospholipase C, suggests that mepacrine also inhibits phosphatidic acid phosphatase, thereby shunting the flux of phosphatidic acid away from diglyceride formation and into synthesis of phosphatidylinositol.
D000098:Acetophenones / Q000494:pharmacology*; D000215:Acylation; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D066298:In Vitro Techniques; D007679:Kidney Medulla / Q000187:drug effects / Q000378:metabolism*; D008041:Linoleic Acids / Q000378:metabolism; D050356:Lipid Metabolism; D008297:Male; D010740:Phospholipases / Q000037:antagonists & inhibitors*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology*; D011817:Rabbits; D013229:Stearic Acids / Q000378:metabolism
D000098:Acetophenones; D001095:Arachidonic Acids; D005227:Fatty Acids; D008041:Linoleic Acids; D013229:Stearic Acids; C031183:stearic acid; D010740:Phospholipases; D010741:Phospholipases A; D054467:Phospholipases A2; D011796:Quinacrine; C006821:4-bromophenacyl bromide