Alterations of Macromolecule Biosynthesis after Chronic Administration of Opiates and Ethanol

  • Horace H. Loh
  • Nancy M. Lee
  • R. Adron Harris
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 85B)

Abstract

The literature concerning the effects of opiates, alcohol and barbiturates on RNA and protein metabolism is reviewed. Recent findings from this laboratory suggest that chronic morphine treatment increases the template activity of chromatin from oligodendroglial nuclei while chronic ethanol treatment decreases this activity. In addition, chronic morphine treatment stimulates protein synthesis in cell free systems and may increase the synthesis of discrete synaptic membrane proteins. Results from other laboratories suggest a general decrease in macromolecule biosynthesis with long term ethanol consumption. These results are discussed in terms of the possible roles of protein synthesis in the effects of chronic opiate and ethanol administration.

Keywords

Chronic Ethanol Physical Dependence Morphine Treatment Orotic Acid Chronic Morphine 
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References

  1. Allfrey, V.G. Some observations on histone acetylation and its temporal relationship to gene activation. In A. San Pietro, M.R. Lanborg and F.T. Kenney (Eds.) Regulatory Mechanisms for Protein Synthesis in Mammalian Cells, pp. 65–100, New York, Academic Press, 1968.Google Scholar
  2. Banker, G. and Cotman, C.W. Characteristics of different amino acids as protein precursors in mouse brain: advantages of certain carboxyl-labeled amino acids. Arch. Biochem. Biophys., 142:565–573, 1971.CrossRefGoogle Scholar
  3. Barondes, S.H. and Dutton, C.R. Protein metabolism in the nervous system. In R.W. Albers, C.J. Siegel, R. Katzman and B.W. Agranoff (Eds.) Basic Neurochemistry, pp. 229–244. Boston, Little Brown & Co., 1972.Google Scholar
  4. Becker, F.F., Rossman, T., Reiss, B. and Simon, E.J. The effect of levorphanol tartrate on ribonucleic acid synthesis in normal and regenerating rat liver. Res. Commun. Chem. Path. Pharmacol., 3:105–116, 1972.Google Scholar
  5. Berl, S. and Clark, D.D. Compartmentalization of amino acid metabolism. In A. Lajtha (Ed.) Handbook of Neurochemistry, Vol. II, pp. 447–472. New York, Plenum Press, 1969.Google Scholar
  6. Castles, T.R., Campbell, S., Gouge, R. and Lee, C.C. Nucleic acid synthesis in brains from rats tolerant to morphine analgesia. J. Pharmacol. Exp. Ther., 181:399–406, 1972.Google Scholar
  7. Chaplin, E.R., Goldberg, A.L. and Diamond, I. Leucine oxidation in brain slices and nerve endings. J. Neurochem. 26:701–707, 1976.CrossRefGoogle Scholar
  8. Chuang, D.M., Hollenbeck, R. and Costa, E. Enhanced template activity in chromatin from adrenal medulla after phosphorylation of chromosomal proteins. Science, 193:60–62, 1976.CrossRefGoogle Scholar
  9. Clouet, D.H. The effects of drugs on protein synthesis in the nervous system. In A. Lajtha (Ed.) Protein Metabolism of the Nervous System, pp. 699–713. New York, Plenum Press, 1970.CrossRefGoogle Scholar
  10. Clouet, D.H. Protein and nucleic acid metabolism. In D.H. Clouet (Ed.) Narcotic Drugs: Biochemical Pharmacology, pp. 216–228. New York, Plenum Press, 1971.Google Scholar
  11. Clouet, D.H. and Ratner, M. The effect of the administration of morphine on the incorporation of (l4C)-leucine into the proteins of rat brain in vivo. Brain Res., 4:33–43, 1967.CrossRefGoogle Scholar
  12. Clouet, D.H. and Ratner, M. The effect of morphine administration on the incorporation of (14C)-leucine into protein in cell-free systems from rat brain and liver. J. Neuroehem., 15:17–23, 1968.CrossRefGoogle Scholar
  13. Cohen, M., Keats, A.S., Krivoy, W. and Ungar, G. Effect of actinomycin-D on morphine tolerance. Proc. Soc. Exp. Biol. Med., 119:381–384, 1965.Google Scholar
  14. Collier, H.O.J., Hammond, M.D. and Schneider, C. Effects of drugs affecting endogenous amines or cyclic nucleotides on ethanol withdrawal head twitches in mice. Brit. J. Pharmacol., 58:9–16, 1976.CrossRefGoogle Scholar
  15. Cox, B.M., Ginsberg, M. and Osman, O.H. Acute tolerance to narcotic analgesic drugs in rat. Brit. J. Pharmacol., 33:245–256, 1968.Google Scholar
  16. Cox, B.M. and Osman, O.H. Inhibition of development of tolerance to morphine in rats by drugs which inhibit ribonucleic acid or protein synthesis. Brit. J. Pharmacol., 38:157–170, 1970.CrossRefGoogle Scholar
  17. Craves, F.B., Meyerhoff, J.L., Loh, H.H. and Trevor, A.J. Effect of morphine on a cell free protein synthetic system isolated from mouse brain. Fed. Proc., 34:2921, 1975.Google Scholar
  18. Darnell, J.E., Philipson, L., Wall, R. and Adesnik, M. Polyadenylic acid sequences: role in conversion of nuclear RNA into messenger RNA. Science, 174:507–510, 1971.CrossRefGoogle Scholar
  19. Datta, R.K. and Antopol, W. Effects of morphine on mouse liver and brain ribonuclease and deoxyribonuclease activities. Tox. Appl. Pharmacol., 18:851–855, 1971.CrossRefGoogle Scholar
  20. Datta, R.K. and Antopol, W. Inhibitory effects of chronic administration of morphine on uridine and thymidine incorporating abilities of mouse liver and brain subcellular fractions. Tox. Appl. Pharmacol., 23:75–81, 1972.CrossRefGoogle Scholar
  21. Datta, R.K. and Antopol, W. Influence of methadone and sulfa-pyridine on mouse liver and brain ribonuclease and deoxyribonuclease. Pharmacology, 9:97–106, 1973a.’CrossRefGoogle Scholar
  22. Datta, R.K. and Antopol, W. Inhibitory effect of chronic administration of morphine on RNA polymerase activities of mouse liver and brain nuclei. Tox. Appl. Pharmacol., 25:71–76, 1973b.CrossRefGoogle Scholar
  23. Datta, R.K. and Antopol, W. Effect of chronic administration of morphine on mouse brain aminoacyl-tRNA synthetase and tRNA-amino acid binding. Brain Res., 53:373–386, 1973c.CrossRefGoogle Scholar
  24. DeLarco, J-, Abramowitz, A., Bromwell, K. and Curoff, G. Polyadenylic acid-containing RNA from rat brain. J. Neurochem., 24:215–222, 1976.CrossRefGoogle Scholar
  25. Dunn, A.J. The chemistry of learning and the formation of memory. In W.H. Gispen (Ed.) Molecular and Functional Neurobiology, pp. 347–387. Amsterdam, Elsevier, 1976.Google Scholar
  26. Dunn, A.J. and Bondy, S.C. Functional Chemistry of the Brain. New York, Spectrum Publications, 1974.Google Scholar
  27. Fehr, K.A., Kalant, H. and LeBlanc, A.E. Residual learning deficit after heavy exposure to cannabis or alcohol in rats. Science, 192:1249–1251, 1976.CrossRefGoogle Scholar
  28. Feinberg, M.P. and Cochin, J. Inhibition of development of tolerance to morphine by cycloheximide. Biochem. Pharmacol., 21:3082–3085, 1972.CrossRefGoogle Scholar
  29. Fleming, E.W., Tewari, S. and Noble, E.P. Effects of chronic ethanol ingestion on brain aminoacyl-tRNA synthetases and tRNA. J. Neurochem., 24:553–560, 1975.CrossRefGoogle Scholar
  30. Franklin, G.I. and Cox, B.M. Incorporation of amino acids into proteins of synaptosomal membranes during morphine treatment. J. Neurochem., 19:1821–1823, 1972.CrossRefGoogle Scholar
  31. Glassman, E. The biochemistry of learning: an evaluation of the role of RNA and protein. Ann. Rev. Biochem., 38:605–646, 1969.CrossRefGoogle Scholar
  32. Goldstein, D.B. Relationship of alcohol dose to intensity of withdrawal signs in mice. J. Pharmacol. Exp. Ther. 180:203–215, 1972.Google Scholar
  33. Goldstein, D.B. Pharmacological aspects of physical dependence on ethanol. Life Sci., 18:553–562, 1976.CrossRefGoogle Scholar
  34. Hahn, D.L. and Goldstein, A. Amounts and turnover rates of brain proteins in morphine-tolerant mice. J. Neurochem., 18:1887–1893, 1971.CrossRefGoogle Scholar
  35. Harris, R.A., Dunn, A. and Harris, L.S. Effects of acute and chronic morphine administration on the incorporation of (3H)-lysine into mouse brain and liver proteins. Res. Comm. Chem. Path. Pharmacol., 9:299–306, 1974.Google Scholar
  36. Harris, R.A., Harris, L.S. and Dunn, A. Effects of narcotic drugs on ribonucleic acid and nucleotide metabolism in mouse brain. J. Pharmacol. Exp. Ther., 192:280–287, 1975.Google Scholar
  37. Hitzemann, R.J. and Loh, H.H. Effect of chronic morphine and pentobarbital treatment on synaptic plasma membrane protein synthesis. Proceedings of the NAS-NRC Committee on Problems of Drug Dependence, pp. 460–473, 1974.Google Scholar
  38. Hitzemann, R.J. and Loh, H.H. On the possible role of brain protein synthesis in functional barbiturate tolerance. Eur. J. Pharmacol., 40:163–173, 1976a.CrossRefGoogle Scholar
  39. Hitzemann, R.J. and Loh, H.H. Influence of morphine on protein synthesis in discrete subcellular fractions of the rat brain. Res. Comm. Chem. Path. Pharmacol., 14:237–248, 1976b.Google Scholar
  40. Ho, I.K. Systematic assessment of tolerance to pentobarbital by pellet implantation. J. Pharmacol. Exp. Ther., 197:479–487, 1976.Google Scholar
  41. Hodgson, J.R., Lee, C-C. and Castles, T.R. Brain chromatin activity of morphine-treated rats. Proc. Soc. Biol. Exp. Med., 141:790–793, 1972.Google Scholar
  42. Hogans, A.F., Guroff, G. and Udenfriend, S. Studies on the origin of pyrimidines for biosynthesis of neural RNA in the rat. J. Neurochem., 18:1699–1710, 1971.CrossRefGoogle Scholar
  43. Hunter, B.E., Riley, J.N., Walker, D.W. and Freund, G. Ethanol dependence in the rat: a parametric analysis. Pharmacol. Biochem. Behav., 3:619–629, 1975.CrossRefGoogle Scholar
  44. Jarlstedt, J. Experimental alcoholism in rats: protein synthesis in subcellular fractions from cerebellum, cerebral cortex and liver after long term treatment. J. Neurochem., 19:603–608, 1972.CrossRefGoogle Scholar
  45. Jarlstedt, J. and Hamberger, A. Experimental alcoholism in rats. Effect of acute ethanol intoxication on the in vitro incorporation of (3H)-leucine into neuronal and glial proteins. J. Neurochem., 19:2299–2316, 1972.CrossRefGoogle Scholar
  46. Kalant, H., LeBlanc, A.E. and Gibbins, R.J. Tolerance and dependence on some non-opiate psychotropic drugs. Pharmacol. Rev., 23:135–191, 1971.Google Scholar
  47. Koenig, H. Neurobiological action of some pyrimidine analogs. Int. Rev. Neurobiol., 10:199–230, 1967.CrossRefGoogle Scholar
  48. Kuriyama, K., Sze, P.Y. and Rauscher, G.E. Effects of acute and chronic ethanol administration on ribosomal protein synthesis in mouse brain and liver. Life Sci., 10:II, 181–189, 1971.CrossRefGoogle Scholar
  49. Kuschinsky, K. Effect of morphine on protein synthesis in synapto-somes and mitochondria of mouse brain in vivo. Naunyn Schmiedebergs Arch. Pharmak., 271:294–300, 1971.CrossRefGoogle Scholar
  50. Lajtha, A. Protein Metabolism of the Nervous System. New York, Plenum Press, 1970.Google Scholar
  51. Lajtha, A. and Marks, N. Protein turnover. In A. Lajtha (Ed.) Handbook of Neurochemistry, Vol. VB, pp. 551–630. New York, Plenum Press, 1971.Google Scholar
  52. Lang, D.W., Darrah, H.K., Hedley-Whyte, J. and Laasberg, L.H. Uptake into brain proteins of 35s-methionine during morphine tolerance. J. Pharmacol. Exp. Ther., 192:521–530, 1975.Google Scholar
  53. Langan, T.A. Phosphorylation of proteins of the cell nucleus. In A. San Pietro, M.R. Lanborg and F.T. Kenney (Eds.) Regulatory Mechanisms for Protein Synthesis in Mammalian Cells, pp. 101–118. New York, Academic Press, 1968.Google Scholar
  54. LeBlanc, A.E., Kalant, H., Gibbins, R.J. and Berman, N.D. Acquisition and loss of tolerance to ethanol by the rat. J. Pharmacol. Exp. Ther., 168:244–250, 1969.Google Scholar
  55. LeBlanc, A.E., Matsunaga, M. and Kalant, H. Effects of frontal polar cortical ablation and cycloheximide on ethanol tolerance in rats. Pharmacol. Biochem. Behav., 4:175–179, 1976.CrossRefGoogle Scholar
  56. Lee, N.M., Ho, I.K. and Loh, H.H. Effect of chronic morphine treatment on brain chromatin template activities in mice. Biochem. Pharmacol., 24:1983–1987, 1975.CrossRefGoogle Scholar
  57. Lee, N.M. and Loh, H.H. A study of deoxyribonucleic acid binding of narcotic analgesics. Biochem. Pharmacol., 24:1249–1251, 1975.CrossRefGoogle Scholar
  58. Loh, H.H. and Hitzemann, R.J. Effect of morphine on the turnover and synthesis of (leu-3H)-protein and (Ch-14C)-phosphatidylcholine in discrete regions of the rat brain. Biochem. Pharmacol., 23:1753–1765, 1974.CrossRefGoogle Scholar
  59. Loh, H.H., Shen, F. and Way, E.L. Inhibition of morphine tolerance and physical dependence development and brain serotonin synthesis by cycloheximide. Biochem. Pharmacol., 18:2711–2721, 1969.CrossRefGoogle Scholar
  60. Loh, H.H., Shen, F-H. and Way, E.L. Effect of dactinomycin on the acute toxicity and brain uptake of morphine. J. Pharmacol. Exp. Ther., 177:326–331, 1971.Google Scholar
  61. Luthra, Y.K., Rosenkrantz, H., Heyman, I.A. and Braude, M.C. Differential neurochemistry and temporal pattern in rats treated orally with Δ9-tetrahydrocannabinol for periods up to six months. Tox. Appl. Pharmacol., 32:418–431, 1975.CrossRefGoogle Scholar
  62. Mahler, H. Nucleic acid metabolism. In R.W. Albers, G.J. Siegel, R. Katzman and B.W. Agranoff (Eds.) Basic Neurochemistry, pp. 245–265. Boston, Little, Brown & Co., 1972.Google Scholar
  63. Majchrowicz, E. Induction of physical dependence upon ethanol and the associated behavioral changes in rats. Psychopharmacol., 43:245–254, 1975.CrossRefGoogle Scholar
  64. Mandel, P. Free nucleotides. In A. Lajtha (Ed.) Handbook of Neurochemistry, Vol. 5, pp. 249–281. New York, Plenum Press, 1971.Google Scholar
  65. Marks, N. and Lajtha, A. Protein and polypeptide breakdown. In A. Lajtha (Ed.) Handbook of Neurochemistry, Vol. VA, pp. 49–139. New York, Plenum Press, 1971.Google Scholar
  66. McEwen, B.S. and Zigmond, R.E. Isolation of brain nuclei. In N. Marks and R. Rodnight (Eds.) Research Methods in Neurochemistry, pp. 139–161. New York, Plenum Press, 1972.CrossRefGoogle Scholar
  67. McMillan, D.E., Waddell, F.B. and Cathcart, C.F. Establishment of physical dependence in mice by oral ingestion of morphine. J. Pharmacol. Exp. Ther., 190:416–419, 1974.Google Scholar
  68. Morland, J. and Sjetnan, A.E. Reduced incorporation of (3H)-leucine into cerebral proteins after long-term ethanol treatment. Biochem. Pharmacol., 25:220–221, 1976.CrossRefGoogle Scholar
  69. Navon, S. and Lajtha, A. Uptake of morphine in particulate fractions from rat brain. Brain Res., 24:534–536, 1970.CrossRefGoogle Scholar
  70. Noble, E.P. and Tewari, S. Protein and ribonucleic acid metabolism in brains of mice following chronic alcohol consumption. Ann. N.Y. Acad. Sci., 215:333–345, 1973.CrossRefGoogle Scholar
  71. Noble, E.P. and Tewari, S. Ethanol and brain ribosomes. Fed. Proc., 34:1942–1947, 1975.Google Scholar
  72. Oguri, K., Lee, N.M. and Loh, H.H. Apparent protein kinase activity in oligodendroglial chromatin after chronic morphine treatment. Biochem. Pharmacol., 25:2371–2376, 1976.CrossRefGoogle Scholar
  73. Oja, S.S. Comments on the measurement of protein synthesis in the brain. Int. J. Neuroscience, 5:31–33, 1973.CrossRefGoogle Scholar
  74. Renis, M., Giovine, A. and Bertolino, A. Protein synthesis in mitochondrial and microsomal fractions from rat brain and liver after acute or chronic ethanol administration. Life Sci., 16:1447–1458, 1975.CrossRefGoogle Scholar
  75. Schimke, R.T. Principles underlying the regulation of synthesis and degradation of protein in animal tissues. In F.O. Schmitt and F.G. Worden (Eds.) The Neurosciences, Third Study Program, pp. 813–825. Cambridge, Mass., MIT Press, 1974.Google Scholar
  76. Shuster, L. and Hannam, R.V. The indirect inhibition of protein synthesis in vivo by chlorpromazine. J. Biol. Chem., 239:3401–3406, 1964.Google Scholar
  77. Shuster, L. Tolerance and physical dependence. In D.H. Clouet (Ed.) Narcotic Drugs: Biochemical Pharmacology, pp. 408–423. New York, Plenum Press, 1971.Google Scholar
  78. Shuster, L., Hannam, R.V. and Boyle, W.E., Jr. A simple method for producing tolerance to dihydromorphinone in mice. J. Pharmacol. Exp. Ther., 140:149–154, 1963.Google Scholar
  79. Siew, C. and Goldstein, D.B. A novel method for rapid development of barbiturate tolerance and physical dependence. Fed. Proc., 35:356, 1976.Google Scholar
  80. Soeiro, R., Vaughan, M.H., Warner, J.R. and Darnell, J.E. The turnover of nuclear DNA-like RNA in HeLa cells. J. Cell. Biol., 39:112–118, 1968.CrossRefGoogle Scholar
  81. Spoerlein, M.T. and Scrafani, J. Effects of time and 8-azaguanine on the development of morphine tolerance. Life Sci., 6:1549–1564, 1967.CrossRefGoogle Scholar
  82. Stein, G.S., Speisberg, T.C. and Kleinsmith, L.J. Nonhistone chromosomal proteins and gene regulation. Science, 183:817–824, 1974.CrossRefGoogle Scholar
  83. Stolman, S. and Loh, H.H. Proceedings of the NAS-NRC Committee on Problems of Drug Dependence, 1:803–814, 1971.Google Scholar
  84. Stolman, S. and Loh, H.H. Stabilization of brain free polysomes by morphine. Res. Comm. Chem. Path. Pharmacol., 12:419–425, 1975.Google Scholar
  85. Tamerin, J.S., Weiner, S., Poppen, R., Steinglass, P. and Mendelson, J.H. Alcohol and memory. Am. J. Psychiat., 127: 1659–1664, 1971.Google Scholar
  86. Teiger, D.G. Induction of physical dependence on morphine, codeine and meperidine in the rat by continuous infusion. J. Pharmacol. Exp. Ther., 190:408–415, 1974.Google Scholar
  87. Tewari, S., Fleming, E.W. and Noble, E.P. Alterations in brain RNA metabolism following chronic ethanol ingestion. J. Neurochem., 24:561–569, 1975.CrossRefGoogle Scholar
  88. Tewari, S. and Noble, E.P. Ethanol and brain protein synthesis. Brain Res., 26:469–474, 1971.Google Scholar
  89. Tewari, S. and Noble, E.P. Chronic ethanol ingestion by rodents: effects on brain RNA. In M.A. Rothschild, M. Oratz and S.S. Schreiber (Eds.) Alcohol and Abnormal Protein Synthesis, pp. 421–448. New York, Pergamon Press, 1974.Google Scholar
  90. Tiplady, B. Brain protein metabolism and environmental stimulation: effects of forced exercise. Brain Res., 43:215–225, 1972.CrossRefGoogle Scholar
  91. Tremblay, G.C., Jimenez, U. and Crandall, D.E. Pyrimidine biosynthesis and its regulation in the developing rat brain. J. Neurochem., 26:57–64, 1976.Google Scholar
  92. Tseng, J.K. and Gurpide, E. Compartmentalization of aridine and uridine 5′-monophosphate in rat liver slices. J. Biol. Chem., 248:5634–5640, 1973.Google Scholar
  93. Walker, D.W. and Freund, G. Impairment of timing behavior after prolonged alcohol consumption in rats. Science, 182:597–599, 1973.CrossRefGoogle Scholar
  94. Way, E.L., Loh, H.H. and Shen, F.H. Simultaneous quantitative assessment of morphine tolerance and physical dependence. J. Pharmacol. Exp. Ther., 167:1–8, 1969.Google Scholar
  95. Wei, E., Loh, H.H. and Way, E.L. Quantitative aspects of precipitated abstinence in morphine dependent rats. J. Pharmacol. Exp. Ther., 184:398–403, 1973.Google Scholar
  96. Yamamoto, I., Inoki, R., Tamari, Y. and Iwatsubo, K. Inhibitory effect of 8-azaguanine on the development of tolerance in the analgesic action of morphine. Jap. J. Pharmacol., 17:140–142, 1967.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1977

Authors and Affiliations

  • Horace H. Loh
    • 1
  • Nancy M. Lee
    • 1
  • R. Adron Harris
    • 1
  1. 1.Department of Pharmacology and Langley Porter Neuropsychiatric InstituteUniversity of CaliforniaSan FranciscoUSA

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