TY - JOUR T1 - Effect of Morphine Derivatives on Lipid Metabolism in <em>Staphylococcus aureus</em> JF - Molecular Pharmacology JO - Mol Pharmacol SP - 134 LP - 145 VL - 6 IS - 2 AU - E. F. GALE Y1 - 1970/03/01 UR - http://molpharm.aspetjournals.org/content/6/2/134.abstract N2 - Heroin at a concentration which inhibits the transport of lysine into Staphylococcus aureus stimulates the incorporation of glycerol into the phospholipid fraction of the cells. The stimulation is accompanied by an increased turnover of the major phospholipid, phosphatidylglycerol. Chromatographic examination of the lipid appears to show the presence of new phospholipids, judged from changes in the profile of elution from silicic acid columns and the appearance of new radioactive spots on silicic acid-impregnated paper chromatograms. Chromatographic analysis of the new components and their hydrolytic products shows that they contain phosphatidylglycerol and diphosphatidylglycerol. (N-Methyl-14C)-heroin is rapidly taken up by staphylococcal cells, but examination of that part of the radioactivity appearing in phospholipids shows that this is contained in glycerol residues. (7,8-3H)-Dihydroheroin is also taken up rapidly, and 3H is found in association with phospholipids; over 50% of this 3H dissociates from phospholipid on deacylation and chromatography in polar solvents. Free heroin reacts with phosphatidylglycerol in vitro to give complexes whose elution profiles are the same as those obtained from drug-treated cells; the "new components," however, are found only when phospholipid turnover takes place in the presence of the drug to give diphosphatidylglycerol. Similar results have been obtained with levorphanol, dextrorphan (the optical isomer of levorphanol), levallorphan, and naloxone. The elution profiles of phospholipid extracts differ with the drug used but can again be reproduced by reaction of drug and phosphatidylglycerol in vitro. "New components" are produced in each case and yield, after deacylation and chromatography in 1-propanol-ammonia-water, mixtures of phosphatidylglycerol and diphosphatidylglycerol. Since the same effects are obtained with narcotics (heroin, levorphanol), morphine antagonists (levallorphan, naloxone), and dextrorphan, which is inactive in man, it would appear that the antibacterial effects are not related to the effects of morphine derivatives in man. ACKNOWLEDGMENTS I am indebted to Mrs. J. Babb for her assistance in carrying out the experimental part of this paper; to Dr. H. W. Kosterlitz for gifts of naloxone and 3H-dihydromorphine and for valuable background information on the pharmacological properties of the drugs used; and to Roche Products Ltd. for gifts of levorphanol, dextrorphan, and levallorphan. ER -