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. 1992 Jul 1;285(Pt 1):161–166. doi: 10.1042/bj2850161

The effect of methyl-lidocaine on the biosynthesis of phospholipids de novo in the isolated hamster heart.

P G Tardi 1, R Y Man 1, P C Choy 1
PMCID: PMC1132760  PMID: 1322123

Abstract

Methyl-lidocaine is an amphiphilic agent which has been used as an experimental anti-arrhythmic drug. When hamster hearts were perfused with labelled glycerol, the presence of methyl-lidocaine in the perfusate was found to enhance the labelling in phosphatidylserine, phosphatidylinositol, diacylglycerol and triacylglycerol. However, the labelling of phosphatidylcholine and phosphatidylethanolamine was not significantly changed by methyl-lidocaine treatment. Assays in vitro for the enzymes involved in the synthesis of neutral lipids and acidic phospholipids revealed that phosphatidate phosphatase and CTP: phosphatidate cytidylyltransferase activities were stimulated by methyl-lidocaine. The intracellular pool sizes of diacylglycerol and CDP-diacylglycerol were also elevated. We postulate that the enhanced syntheses of the neutral lipids and acidic phospholipids in the methyl-lidocaine-perfused heart were mediated via the direct activation of the key enzymes in the biosynthesis of these lipids de novo.

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Selected References

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  1. Akesson B., Elovson J., Arvidson G. Initial incorporation into rat liver glycerolipids of intraportally injected (3H)glycerol. Biochim Biophys Acta. 1970 Jun 9;210(1):15–27. doi: 10.1016/0005-2760(70)90057-3. [DOI] [PubMed] [Google Scholar]
  2. Allan D., Michell R. H. Enhanced synthesis de novo of phosphatidylinositol in lymphocytes treated with cationic amphiphilic drugs. Biochem J. 1975 Jun;148(3):471–478. doi: 10.1042/bj1480471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Arthur G., Choy P. C. Acyl specificity of hamster heart CDP-choline 1,2-diacylglycerol phosphocholine transferase in phosphatidylcholine biosynthesis. Biochim Biophys Acta. 1984 Sep 12;795(2):221–229. doi: 10.1016/0005-2760(84)90069-9. [DOI] [PubMed] [Google Scholar]
  4. Arvidson G. A. Structural and metabolic heterogeneity of rat liver glycerophosphatides. Eur J Biochem. 1968 May;4(4):478–486. doi: 10.1111/j.1432-1033.1968.tb00237.x. [DOI] [PubMed] [Google Scholar]
  5. BARTLETT G. R. Phosphorus assay in column chromatography. J Biol Chem. 1959 Mar;234(3):466–468. [PubMed] [Google Scholar]
  6. Batenburg J. J., den Breejen J. N., Yost R. W., Haagsman H. P., van Golde L. M. Glycerol 3-phosphate acylation in microsomes of type II cells isolated from adult rat lung. Biochim Biophys Acta. 1986 Oct 3;878(3):301–309. doi: 10.1016/0005-2760(86)90237-7. [DOI] [PubMed] [Google Scholar]
  7. Belendiuk G., Mangnall D., Tung B., Westley J., Getz G. S. CTP-phosphatidic acid cytidyltransferase from Saccharomyces cerevisiae. Partial purification, characterization, and kinetic behavior. J Biol Chem. 1978 Jul 10;253(13):4555–4565. [PubMed] [Google Scholar]
  8. Berridge M. J., Irvine R. F. Inositol phosphates and cell signalling. Nature. 1989 Sep 21;341(6239):197–205. doi: 10.1038/341197a0. [DOI] [PubMed] [Google Scholar]
  9. Bowley M., Cooling J., Burditt S. L., Brindley D. N. The effects of amphiphilic cationic drugs and inorganic cations on the activity of phosphatidate phosphohydrolase. Biochem J. 1977 Sep 1;165(3):447–454. doi: 10.1042/bj1650447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Brindley D. N., Bowley M. Drugs affecting the synthesis of glycerides and phospholipids in rat liver. The effects of clofibrate, halofenate, fenfluramine, amphetamine, cinchocaine, chlorpromazine, demethylimipramine, mepyramine and some of their derivatives. Biochem J. 1975 Jun;148(3):461–469. doi: 10.1042/bj1480461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Cascales C., Mangiapane E. H., Brindley D. N. Oleic acid promotes the activation and translocation of phosphatidate phosphohydrolase from the cytosol to particulate fractions of isolated rat hepatocytes. Biochem J. 1984 May 1;219(3):911–916. doi: 10.1042/bj2190911. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Coleman R. Membrane-bound enzymes and membrane ultrastructure. Biochim Biophys Acta. 1973 Apr 3;300(1):1–30. doi: 10.1016/0304-4157(73)90010-5. [DOI] [PubMed] [Google Scholar]
  13. Comfurius P., Zwaal R. F. The enzymatic synthesis of phosphatidylserine and purification by CM-cellulose column chromatography. Biochim Biophys Acta. 1977 Jul 20;488(1):36–42. doi: 10.1016/0005-2760(77)90120-5. [DOI] [PubMed] [Google Scholar]
  14. Eichberg J., Hauser G. Stimulation by local anesthetics of the metabolism of acidic phospholipids in the rat pineal gland. Biochem Biophys Res Commun. 1974 Oct 23;60(4):1460–1467. doi: 10.1016/0006-291x(74)90362-3. [DOI] [PubMed] [Google Scholar]
  15. Freinkel N., El Younsi C., Dawson M. C. Inter-relations between the phospholipids of rat pancreatic islets during glucose stimulation, and their response to medium inositol and tetracaine. Eur J Biochem. 1975 Nov 1;59(1):245–252. doi: 10.1111/j.1432-1033.1975.tb02448.x. [DOI] [PubMed] [Google Scholar]
  16. Geelen M. J., Groener J. E., de Haas C. G., Wisserhof T. A., van Golde L. M. Influence of insulin and glucagon on the synthesis of glycerolipids in rat hepatocytes. FEBS Lett. 1978 Jun 1;90(1):57–60. doi: 10.1016/0014-5793(78)80297-x. [DOI] [PubMed] [Google Scholar]
  17. Groener J. E., Klein W., Van Golde L. M. The effect of fasting and refeeding on the composition and synthesis of triacylglycerols, phosphatidylcholines, and phosphatidylethanolamines in rat liver. Arch Biochem Biophys. 1979 Nov;198(1):287–295. doi: 10.1016/0003-9861(79)90421-1. [DOI] [PubMed] [Google Scholar]
  18. Heathers G. P., Al-Muhtaseb N., Brunt R. V. The effect of adrenergic agents on the activities of glycerol 3-phosphate acyltransferase and triglyceride lipase in the isolated perfused rat heart. J Mol Cell Cardiol. 1985 Aug;17(8):785–796. doi: 10.1016/s0022-2828(85)80040-7. [DOI] [PubMed] [Google Scholar]
  19. Imai A., Gershengorn M. C. Independent phosphatidylinositol synthesis in pituitary plasma membrane and endoplasmic reticulum. Nature. 1987 Feb 19;325(6106):726–728. doi: 10.1038/325726a0. [DOI] [PubMed] [Google Scholar]
  20. Ishidate K., Weinhold P. A. The content of diacylglycerol, triacylglycerol and monoacylglycerol and a comparison of the structural and metabolic heterogeneity of diacylglycerols and phosphatidylcholine during rat lung development. Biochim Biophys Acta. 1981 Apr 23;664(1):133–147. doi: 10.1016/0005-2760(81)90036-9. [DOI] [PubMed] [Google Scholar]
  21. Katz A. M., Messineo F. C. Myocardial membrane function and drug action in heart failure. Am Heart J. 1981 Sep;102(3 Pt 2):491–500. doi: 10.1016/0002-8703(81)90737-7. [DOI] [PubMed] [Google Scholar]
  22. Kelley M. J., Carman G. M. Purification and characterization of CDP-diacylglycerol synthase from Saccharomyces cerevisiae. J Biol Chem. 1987 Oct 25;262(30):14563–14570. [PubMed] [Google Scholar]
  23. Koul O., Hauser G. Modulation of rat brain cytosolic phosphatidate phosphohydrolase: effect of cationic amphiphilic drugs and divalent cations. Arch Biochem Biophys. 1987 Mar;253(2):453–461. doi: 10.1016/0003-9861(87)90199-8. [DOI] [PubMed] [Google Scholar]
  24. Kunze H., Nahas N., Traynor J. R., Wurl M. Effects of local anaesthetics on phospholipases. Biochim Biophys Acta. 1976 Jul 20;441(1):93–102. doi: 10.1016/0005-2760(76)90284-8. [DOI] [PubMed] [Google Scholar]
  25. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  26. Martin A., Hales P., Brindley D. N. A rapid assay for measuring the activity and the Mg2+ and Ca2+ requirements of phosphatidate phosphohydrolase in cytosolic and microsomal fractions of rat liver. Biochem J. 1987 Jul 15;245(2):347–355. doi: 10.1042/bj2450347. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Miura T., Kanfer J. Studies on base-exchange reactions of phospholipids in rat brain. Heterogeneity of base-exchange enzymes. Arch Biochem Biophys. 1976 Aug;175(2):654–660. doi: 10.1016/0003-9861(76)90556-7. [DOI] [PubMed] [Google Scholar]
  28. O K. M., Choy P. C. Solubilization and partial purification of cholinephosphotransferase in hamster tissues. Lipids. 1990 Feb;25(2):122–124. doi: 10.1007/BF02562217. [DOI] [PubMed] [Google Scholar]
  29. Oppenheim W. L. Neurodepressant and local anesthetic activity of the quaternary ammonium salt, methyllidocaine chloride. Arch Int Pharmacodyn Ther. 1970 Nov;188(1):156–162. [PubMed] [Google Scholar]
  30. Sturton R. G., Brindley D. N. Factors controlling the activities of phosphatidate phosphohydrolase and phosphatidate cytidylyltransferase. The effects of chlorpromazine, demethylimipramine, cinchocaine, norfenfluramine, mepyramine and magnesium ions. Biochem J. 1977 Jan 15;162(1):25–32. doi: 10.1042/bj1620025. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Sturton R. G., Pritchard P. H., Han L. Y., Brindley D. N. The involvement of phosphatidate phosphohydrolase and phospholipase A activities in the control of hepatic glycerolipid synthesis. Effects of acute feeding with glucose, fructose, sorbitol, glycerol and ethanol. Biochem J. 1978 Aug 15;174(2):667–670. doi: 10.1042/bj1740667. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Söling H. D., Machado-DeDomenech E., Kleineke J., Fest W. Early effects of beta-adrenergic and muscarinic secretagogues on lipid and phospholipid metabolism in guinea pig parotid acinar cells. Stimulation of 2,3-sn-diacylglycerol formation by isoproterenol. J Biol Chem. 1987 Dec 15;262(35):16786–16792. [PubMed] [Google Scholar]
  33. Tardi P. G., Man R. Y., McMaster C. R., Choy P. C. The effect of methyl lidocaine on lysophospholipid metabolism in hamster heart. Biochem Cell Biol. 1990 Apr;68(4):745–750. doi: 10.1139/o90-107. [DOI] [PubMed] [Google Scholar]
  34. Tijburg L. B., Geelen M. J., van Golde L. M. Regulation of the biosynthesis of triacylglycerol, phosphatidylcholine and phosphatidylethanolamine in the liver. Biochim Biophys Acta. 1989 Jul 17;1004(1):1–19. doi: 10.1016/0005-2760(89)90206-3. [DOI] [PubMed] [Google Scholar]
  35. Yada R., Ide H., Nakazawa Y. In vitro effects of chlorpromazine on glycerol-3-phosphate acyl transferase and 1-acylglycerol-3-phosphate acyltransferase in rat liver microsomes. Biochem Pharmacol. 1986 Nov 15;35(22):4083–4087. doi: 10.1016/0006-2952(86)90032-8. [DOI] [PubMed] [Google Scholar]
  36. Zelinski T. A., Savard J. D., Man R. Y., Choy P. C. Phosphatidylcholine biosynthesis in isolated hamster heart. J Biol Chem. 1980 Dec 10;255(23):11423–11428. [PubMed] [Google Scholar]

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