Skip to main content
SpringerLink
Log in

Phospholipid Metabolism in Nervous Tissues: Modification of Precursor Incorporation and Enzyme Activities by Cationic Amphiphilic Drugs

  • Conference paper
Phospholipid Research and the Nervous System

Part of the book series: FIDIA Research Series ((FIDIA,volume 4))

Abstract

Although the effects of individual drugs on the incorporation of precursors into lipids in vitro have been sporadically examined for thirty years or so, it is primarily during the last ten years that a substantial body of information has been accumulated in this field. During this time, it has come to be recognized that numerous drugs with varied therapeutic actions share the capacity to redirect phospholipid metabolism. The compounds involved exhibit certain common physical-chemical features of their structures, namely a bulky lipophilic ring system and an aliphatic side-chain containing a quaternary, positively charged nitrogen which bestows hydrophilic character upon the molecule. The typical shift in incorporation of 32Pi into phospholipids, elicited by drugs of this type, manifests itself in enhanced labeling of acidic and reduced labeling of neutral phospholipids. This has been demonstrated in numerous biological systems (Hauser and Pappu, 1982; Abdel-Latif, 1983; Bazan et al., 1985).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abdel-Latif AA (1983) Metabolism of phosphoinositides. In: Lajtha A (ed): Handbook of Neurochemistry, Vol. 3. Plenum Publishing Corp, New York, pp. 91–131.

    Google Scholar 

  • Abdel-Latif AA, Smith JP (1976) Effects of DL-propranolol on the synthesis of glycerolipids by rabbit iris muscle. Biochem Pharmacol 25: 1697–1704.

    Article  PubMed  CAS  Google Scholar 

  • Ashcroft RG, Coster HGL, Smith JR (1977) The molecular organization of bimolecular lipid membranes. Biochim Biophys Acta 469: 13–22.

    Article  PubMed  CAS  Google Scholar 

  • Bazan NG, Roccamo de Fernandez AM, Giusto NM, Ilincheta de Boschero MG (1985) Propranolol-induced membrane perturbation and the metabolism of phosphoinositides and arachidonoyl diacylglycerols in the retina. In: Bleasdale J, Eichberg J, Hauser G (eds): Inositol and Phosphoinositides: Metabolism and Regulation. Humana, Clifton, NJ, pp. 67–82.

    Chapter  Google Scholar 

  • Blohm TR (1979) Drug-induced lysosomal lipidosis: biochemical interpretations. Pharmacol Rev 30: 593–603.

    Google Scholar 

  • Bowley M, Cooling J, Burditt SL, Brindley DN (1977) The effects of amphiphilic cationic drugs and inorganic cations on the activity of phosphatidate phosphohydrolase. Biochem J 165: 447–454.

    PubMed  CAS  Google Scholar 

  • Brindley DN, Bowley M (1975) Drugs affecting the synthesis of glycerides and phospholipids in rat liver. Biochem J 148: 461–469.

    PubMed  CAS  Google Scholar 

  • Brumley G, van den Bosch H (1977) Lysophospholipase-transacylase from rat lung, isolation and partial purification. J Lipid Res 18: 523–532.

    PubMed  CAS  Google Scholar 

  • Casals C, Acebal C, Cruz-Alvarez M, Estrada P, Arche R (1982) Lysolecithin: lysolecithin acyltransferase from rabbit lung: Enzymatic properties and kinetic study. Arch Biochem Biophys 217: 422–433.

    Article  PubMed  CAS  Google Scholar 

  • Cascales C, Mangiapane EH, Brindley DN (1984) Oleic acid promotes the activation and translocation of phosphatidate phosphohydrolase from the cytosol to paniculate fractions of isolated rat hepatocytes. Biochem J 219: 911–916.

    PubMed  CAS  Google Scholar 

  • Choy PC, Farren SB, Vance DE (1979) Lipid requirements for the aggregation of CTP: phosphocholine cytidylyltransferase in rat liver cytosol. Can J Biochem 57: 605–612.

    Article  PubMed  CAS  Google Scholar 

  • Choy PC, Lim PH, Vance DE (1977) Purification and characterization of CTP: cholinephosphate cytidylyltranferase from rat liver cytosol. J Biol Chem 252: 7673–7677.

    PubMed  CAS  Google Scholar 

  • Choy PC, Vance DE (1978) Lipid requirements for activation of CTP: phosphocholine cytidylyltransferase from rat liver. J Biol Chem 253: 5163–5167.

    PubMed  CAS  Google Scholar 

  • Conrad MJ, Singer SJ (1981) The solubility of amphipathic molecules in biological membranes and lipid bilayers and its implications for membrane structure. Biochemistry 20: 808–818.

    Article  PubMed  CAS  Google Scholar 

  • Dawson RMC (1956) The phospholipase B of liver. Biochem J 64: 192–196.

    PubMed  CAS  Google Scholar 

  • De Jong JGN, van den Bosch H, Aarsman AJ, van Deenen LLM (1973) Studies on lysophospholipases. II. Substrate specificity of a lysolecithin hydrolyzing carboxylesterase from beef pancreas. Biochim Biophys Acta 296: 105–115.

    Article  PubMed  Google Scholar 

  • Drenckhahn D, Lüllmann-Rauch R (1979) Drug-induced experimental lipidosis in the nervous system. Neuroscience 4: 697–712.

    Article  PubMed  CAS  Google Scholar 

  • Eichberg J, Gates J, Hauser G (1979) The mechanism of modification by propranolol of the metabolism of phosphatidyl-CMP (CDP-diacylglycerol) and other lipids in the rat pineal gland. Biochim Biophys Acta 573: 90–106.

    Article  PubMed  CAS  Google Scholar 

  • Eichberg J, Shein H, Schwartz M, Hauser G (1973) Stimulation of 32Pj incorporation into phosphatidylinositol and phosphatidylglycerol by catecholamines and beta-adrenergic receptor blocking agents in rat pineal organ cultures. J Biol Chem 248: 3615–3622.

    PubMed  CAS  Google Scholar 

  • Erbland J, Marinetti GV (1962) In vitro metabolism of lysolecithin. Federation Proc 21: 295.

    Google Scholar 

  • Fiscus WG, Schneider WC (1966) The role of phospholipids in stimulating phosphorylcholine cytidyltransferase activity. J Biol Chem 241: 3324–3330.

    PubMed  CAS  Google Scholar 

  • Giusto NM, Ilincheta de Boschero MG, Bazan NG (1983) Accumulation of phosphatidic acid from propranolol-treated retinas during short-term incubations. J Neurochem 40: 563–568.

    Article  PubMed  CAS  Google Scholar 

  • Gross RW, Sobel BE (1982) Lysophosphatidylcholine metabolism in the rabbit heart. J Biol Chem 257: 6702–6708.

    PubMed  CAS  Google Scholar 

  • Hall M, Taylor SJ, Saggerson ED (1985) Persistent activity modification of phosphatidate phosphohydrolase and fatty acyl-CoA synthetase on incubation of adipocytes with the tumour promoter 12-O-tetradecanoylphorbol 13-acetate. FEBS Lett 179: 351–353.

    Article  PubMed  CAS  Google Scholar 

  • Hauser G, Eichberg J (1975) Identification of cytidine diphosphatediglyceride in the pineal gland of the rat and its accumulation in the presence of DL-propranol. J Biol Chem 250: 105–112.

    PubMed  CAS  Google Scholar 

  • Hauser G, Pappu AS (1982) Effects of propranolol and other cationic amphiphilic drugs on phospholipid metabolism In: Horrocks LA, Ansell GB, Porcellati G (eds): Phospholipids in the Nervous System, Vol. 1. Metabolism. Raven Press, New York, pp. 283–300.

    Google Scholar 

  • Hokin-Neaverson M (1980) Actions of chloropromazine, haloperidol and pimozide on lipid metabolism in guinea pig brain slices. Biochem Pharmacol 29: 2697–2700.

    Article  PubMed  CAS  Google Scholar 

  • Hostetler KY, Matsuzawa Y (1981) Studies on the mechanism of drug-induced lipidosis. Biochem Pharmacol 30: 1121–1126.

    Article  PubMed  CAS  Google Scholar 

  • Hostetler KY, Zenner BD, Morris HP (1976) Increased mitochondrial CTP: phosphatidic acid cytidyltransferase in the 777 hepatoma. Biochem Biophys Res Commun 72: 418–425.

    Article  PubMed  CAS  Google Scholar 

  • Ide H, Nakazawa Y (1985) Phosphatidate phosphatase in rat liver: The relationship between the activities with membrane-bound phosphatidate and aqueous dispersion of phosphatidate. J Biochem (Tokyo) 97: 45–54.

    CAS  Google Scholar 

  • Jarvis AA, Cain C, Dennis EA (1984) Purification and characterization of a lysophospholipase from human amnionic membranes. J Biol Chem 259: 15188–15195.

    PubMed  CAS  Google Scholar 

  • Kai M, Salway JG, Hawthorne JN (1968) The diphosphoinositide kinase of rat brain. Biochem J 106: 791–801.

    PubMed  CAS  Google Scholar 

  • Kanoh H, Kondoh H, Ono T (1983) Diacylglycerol kinase from pig brain. J Biol Chem 258: 1767–1774.

    PubMed  CAS  Google Scholar 

  • Kunze H, Nahas N, Traynor JR, Wurl M (1976) Effects of local anaesthetics on phospholipases. Biochim Biophys Acta 441: 93–102.

    Article  PubMed  CAS  Google Scholar 

  • Lamb RG, Fallon HJ (1974) Glycerolipid formation from sn-glycerol-3-phosphate by rat liver cell fractions: Role of phosphatidate phosphohydrolase. Biochim Biophys Acta 348: 166–178.

    Article  PubMed  CAS  Google Scholar 

  • Lands WM (1960) Metabolism of glycerolipids. II. The enzymatic acylation of lysolecithin. J Biol Chem 235: 2233–2237.

    PubMed  CAS  Google Scholar 

  • Lee AG (1976) Model for action of local anaesthetics. Nature (Lond) 262: 545–548.

    Article  CAS  Google Scholar 

  • Lee AG (1977a) Lipid phase transitions and phase diagrams. I. Biochim Biophys Acta 472: 237–281.

    Article  CAS  Google Scholar 

  • Lee AG (1977b) Lipid phase transitions and phase diagrams. II. Mixtures involving lipids. Biochim Biophys Acta 472: 285–344.

    Article  PubMed  CAS  Google Scholar 

  • Lee AG (1979) A consumers guide to models of local anesthetic action. Anesthesiology 51: 64–71.

    Article  PubMed  CAS  Google Scholar 

  • Leibowitz-BenGershon Z, Kobiler I, Gatt S (1972) Lysophospholipases of rat brain. J Biol Chem 247: 6840–6847.

    Google Scholar 

  • Leibowitz Z, Gatt S (1968) Isolation of lysophospholipase, free of phospholipase activity from rat brain. Biochim Biophys Acta 164: 439–441.

    Article  Google Scholar 

  • Lüllmann H, Lüllmann-Rauch R, Wassermann O (1975) Drug-induced phospholipidoses. CRC Crit Rev Toxicol 4: 185–218.

    PubMed  Google Scholar 

  • Lüllmann H, Lüllman-Rauch R, Wassermann O (1978) Lipidosis induced by amphiphilic cationic drugs. Biochem Pharmacol 27: 1103–1108.

    Article  PubMed  Google Scholar 

  • Lüllmann H, Weling M (1979) The binding of drugs to different polar lipids in vitro. Biochem Pharmacol 28: 3409–3415.

    Article  PubMed  Google Scholar 

  • Lüllmann-Rauch R (1979) Drug-induced lysosomal storage diseases. In: Dingle JT, Jacques PJ (eds): Lysosomes in Biology and Pathology. Vol. 6, North-Holland, Amsterdam, pp. 49–130.

    Google Scholar 

  • Martin-Sanz P, Hopewell R, Brindley DN (1985) Spermine promotes the translocation of phosphatidate phosphohydrolase from the cytosol to the microsomal fraction of rat liver and it enhances the effects of oleate in this respect. FEBS Lett 179: 262–266.

    Article  PubMed  CAS  Google Scholar 

  • Martonosi A, Donley J, Halpin RA (1968) Sarcoplasmic reticulum. III. The role of phospholipids in the adenosine triphosphatase activity and Ca++-transport. J Biol Chem 243: 61–70.

    PubMed  CAS  Google Scholar 

  • Mitchell MP, Brindley DN, Hübscher G (1971) Properties of phosphatidate phosphohydrolase. Eur J Biochem 18: 214–220.

    Article  PubMed  CAS  Google Scholar 

  • Pakalapati G, Debuch H (1982) Studies on the liberation of fatty acids from 2-lysophosphatidylcholine by a liver lysosomal enzyme activity from chloroquine-treated rats. Hoppe-Seyler’s Z Physiol Chem 363: 573–580.

    Article  PubMed  CAS  Google Scholar 

  • Pang KY, Miller KW (1978) Cholesterol modulates the effects of membrane perturbers in phospholipid vesicles and biomembranes. Biochim Biophys Acta 511: 1–9.

    Article  PubMed  CAS  Google Scholar 

  • Pappu AS, Hauser G (1981a) Alterations of phospholipid metabolism in rat cerebral cortex mince induced by cationic amphiphilic drugs. J Neurochem 37: 1006–1014.

    Article  PubMed  CAS  Google Scholar 

  • Pappu AS, Hauser G (1981b) Changes in brain polyphosphoinositide metabolism induced by cationic amphiphilic drugs in vitro. Biochem Pharmacol 30: 3243–3246.

    Article  PubMed  CAS  Google Scholar 

  • Pappu AS, Hauser G (1982) Phospholipid metabolism changes in rat tissues in vitro after injections of propranolol. J Pharmacol Exptl Ther 222: 109–115.

    CAS  Google Scholar 

  • Pappu AS, Hauser G (1983) Propranolol-induced inhibition of rat brain cytoplasmic phosphatidate phosphohydrolase. Neurochem Res 8: 1565–1575.

    Article  PubMed  CAS  Google Scholar 

  • Pappu A, Hostetler KY (1984) Effect of cationic amphiphilic drugs on the hydrolysis of acidic and neutral phospholipids by liver lysosomal phospholipase A. Biochem Pharm 33: 1639–1644.

    Article  PubMed  CAS  Google Scholar 

  • Pelech SL, Cook HW, Paddon HB, Vance DE (1984a) Membrane-bound CTP: phosphocholine cytidylyltransferase regulates the rate of phosphatidylcholine synthesis in HeLa cells treated with unsaturated fatty acids. Biochim Biophys Acta 795: 433–440.

    Article  PubMed  CAS  Google Scholar 

  • Pelech SL, Paddon HB, Vance DE (1984b) Phorbol esters stimulate phosphatidylcholine biosynthesis by translocation of CTP: phosphocholine cytidylyltransferase from cytosol to microsomes. Biochim Biophys Acta 795: 447–451.

    Article  PubMed  CAS  Google Scholar 

  • Pelech SL, Pritchard PH, Brindley DN, Vance DE (1983) Fatty acids promote translocation of CTP: phosphocholine cytidylyltransferase to the endoplasmic reticulum and stimulate rat hepatic phosphatidylcholine synthesis. J Biol Chem 258: 6782–6788.

    PubMed  CAS  Google Scholar 

  • Pelech SL, Vance DE (1984) Trifluoperazine and chlorpromazine inhibit phosphatidylcholine biosynthesis and CTP: phosphocholine cytidylyltransferase in HeLa cells. Biochim Biophys Acta 795: 441–446.

    Article  PubMed  CAS  Google Scholar 

  • Reddy PV, Natarajan V, Schmid PC, Schmid HHO (1983) N-Acylation of dog heart ethanolamine phospholipids by transacylase activity. Biochim Biophys Acta 750: 472–480.

    Article  PubMed  CAS  Google Scholar 

  • Rooney EK, Lee AG (1983) Binding of hydrophobic drugs to lipid bilayers and to the (Ca2+ +Mg2+)-ATPase. Biochim Biophys Acta 732: 428–440.

    Article  PubMed  CAS  Google Scholar 

  • Seeman P, Roth S (1972) General anesthetics expand cell membranes at surgical concentrations. Biochim Biophys Acta 255: 171–177.

    Article  PubMed  CAS  Google Scholar 

  • Seydel JK, Wassermann O (1976) NMR studies on the molecular basis of drug-induced phospholipidosis. II. Interaction between several amphiphilic drugs and phospholipids. Biochem Pharmacol 25: 2357–2364.

    Article  PubMed  CAS  Google Scholar 

  • Shapiro B (1953) Purification and properties of a lysolecithinase from pancreas. Biochem J 53: 663–666.

    PubMed  CAS  Google Scholar 

  • Singer MA (1977) Interaction of dibucaine and propranolol with phospholipid bilayer membranes — effect of alterations in fatty acyl composition. Biochem Pharmacol 26: 51–57.

    Article  PubMed  CAS  Google Scholar 

  • Smith ME, Sedgwick B, Brindley DN, Hübscher G (1967) The role of phosphatidate phosphohydrolase in glyceride biosynthesis. Eur J Biochem 3: 10–11.

    Article  Google Scholar 

  • Sturton RG, Brindley DN (1977) Factors controlling the activities of phosphatidate phosphohydrolase and phosphatidate cytidylyltransferase. Biochem J 162: 25–32.

    PubMed  CAS  Google Scholar 

  • Surewicz WK (1982) Quinidine is a strong perturber of acidic phospholipid bilayer order and fluidity. Biochim Biophys Acta 692: 315–318.

    Article  PubMed  CAS  Google Scholar 

  • Tanaka R, Strickland KP (1965) Role of phospholipid in the activation of Na+, Reactivated adenosine triphosphatase of beef brain. Arch Biochem Biophys 111: 583–592.

    Article  PubMed  CAS  Google Scholar 

  • The R, Hasselbach W (1972) Properties of the sarcoplasmic ATPase reconstituted by oleate and lysolecithin after lipid depletion. Eur J Biochem 28: 357–363.

    Article  PubMed  CAS  Google Scholar 

  • van den Bosch H, Aarsman AJ, De Jong JGN, van Deenen LLM (1973) Studies on lysophospholipases. I. Purificaton and some properties of a lysophospholipase from beef pancreas. Biochim Biophys Acta 296: 94–104.

    Article  PubMed  Google Scholar 

  • van den Bosch H, Aarsman AJ, Slotboom AJ, van Deenen LLM (1968) On the specificity of rat liver lysophospholipase. Biochim Biophys Acta 164: 215–225.

    Article  PubMed  Google Scholar 

  • van Heusden GPH, Reutelingsperger CPM, van den Bosch H (1981) Substrate specificity of lysophospholipase-transacylase from rat lung and its action on various physical forms of lysophosphatidylcholine. Biochim Biophys Acta 663: 22–33.

    Article  PubMed  Google Scholar 

  • Vianen GM, van den Bosch H (1978) Lysophospholipase and lysophosphatidylcholine: lysophosphatidylcholine transacylase from rat lung: Evidence for a single enzyme and some aspects of its specificity. Arch Biochem Biophys 190: 373–384.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Ralph Lowell Laboratories, McLean Hospital, Harvard Medical School, Belmont, MA, 02178, USA

    George Hauser, Omanand Koul & Ubaldo Leli

Authors
  1. George Hauser
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Omanand Koul
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ubaldo Leli
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Physiological Chemistry, College of Medicine, The Ohio State University, Columbus, Ohio, USA

    Lloyd A. Horrocks

  2. Centre de Neurochimie du CNRS, Strasbourg, France

    Louis Freysz

  3. Fidia Research Laboratories, Abano Terme, Italy

    Gino Toffano

Rights and permissions

Reprints and permissions

Copyright information

© 1986 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Hauser, G., Koul, O., Leli, U. (1986). Phospholipid Metabolism in Nervous Tissues: Modification of Precursor Incorporation and Enzyme Activities by Cationic Amphiphilic Drugs. In: Horrocks, L.A., Freysz, L., Toffano, G. (eds) Phospholipid Research and the Nervous System. FIDIA Research Series, vol 4. Springer, New York, NY. https://doi.org/10.1007/978-1-4899-0490-4_10

Download citation

  • DOI: https://doi.org/10.1007/978-1-4899-0490-4_10

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4899-0492-8

  • Online ISBN: 978-1-4899-0490-4

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation