Phospholipid Metabolism in Nervous Tissues: Modification of Precursor Incorporation and Enzyme Activities by Cationic Amphiphilic Drugs
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).
KeywordsRetina Cytosol Choline Haloperidol Oleate
Unable to display preview. Download preview PDF.
- 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
- 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.CrossRefGoogle Scholar
- Blohm TR (1979) Drug-induced lysosomal lipidosis: biochemical interpretations. Pharmacol Rev 30: 593–603.Google Scholar
- Erbland J, Marinetti GV (1962) In vitro metabolism of lysolecithin. Federation Proc 21: 295.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
- 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.Google Scholar
- Leibowitz-BenGershon Z, Kobiler I, Gatt S (1972) Lysophospholipases of rat brain. J Biol Chem 247: 6840–6847.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
- Pappu AS, Hauser G (1982) Phospholipid metabolism changes in rat tissues in vitro after injections of propranolol. J Pharmacol Exptl Ther 222: 109–115.Google Scholar