SELECTIVE INHIBITORS OF LECITHIN BIOSYNTHESIS IN MOUSE PERITONEAL-MACROPHAGES

Mouse peritoneal macrophages turn over their membrane components rapidly. The biosynthetic pathway for phosphatidylcholine synthesis from choline can be inhibited in a non-toxic manner by a series of diphenylsulfones. The parent compound of this series, dapsone, and its derivative, 1-[4-(4-sulfanilyl)phenyl] urea (AUS), inhibit the synthesis of lecithin from choline by mouse peritoneal macrophages in a dose- and time-dependent manner. This inhibition of choline incorporation does not appear to be due to an effect on transport of choline into the cells nor is it an effect on general membrane synthesis. In addition, the sulfones inhibit the incorporation of [32P]phosphate into phospatidylcholine but do not significantly inhibit its incorporation into sphingomyelin, phosphatidylinositol or phosphatidylethanolamine. This inhibition of lecithin synthesis is reversible and appears to require functionally intact membranes. © 1979.