Enhanced synthesis de novo of phosphatidylinositol in lymphocytes treated with cationic amphiphilic drugs

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Authors

Colleges, School and Institutes

Abstract

A variety of amphiphilic cations caused very large increases in the rates of incorporation of P and glycerol into phosphatidylinositol in pig mesenteric small lymphocytes. This synthesis de novo or phosphatidylinositol led to a doubling of the phosphatidylinositol concentration in the cells within 3.5 hr. The increase in synthesis of phosphatidylinositol labelled with [3H] or [14C]glycerol was matched by an approximately equivalent decrease in incorporation of glycerol into phosphatidylcholine, phosphatidylethanol amine and triacylglycerol. Amphilic cations which produced these effects included, in order of decreasing effectiveness, trifluoperazine (half maximal effect at about 70 μM) > chlorpromazine =± promethazine =± imipramine > cinchocaine > amethocaine =± cetyltrimethylammonium > fenfluramine > amphetamine > 2 phenethylamine > cocaine =± procaine; the most effective compounds were those with the largest and most hydrophobic nonpolar substituents. The response to cations was not changed by varying the extracellular Ca2+ concentration in the range 10 nM to 1 mM. The active amphiphilic cations interacted with anionic phospholipids causing aggregation of aqueous dispersions and/or changes in chromatographic behavior. These results indicate that amphiphilic cations redirect glyerolipid synthesis de novo, probably owing to inhibition of phosphatidate phosphohydrolase, so that phosphatidylinositol synthesis is increased at the expense of other glycerolipids.

Details

Original languageEnglish
Pages (from-to)471-478
Number of pages8
JournalBiochemical Journal
Volume148
Issue number3
Publication statusPublished - 1 Jan 1975