Advertisement

Choline Availability — Choline High Affinity Transport and the Regulation of Acetylcholine Synthesis

  • L. A. Barker

Abstract

The use of precursor-loading with choline as a therapeutic modality raises the question of whether the plasma levels of choline directly regulate the synthesis of (ACh) in brain. In this chapter, the issues of choline availability and the transport of choline by cholinergic nerve endings in the regulation of (ACh) formation will be discussed. Data are presented which suggest that under normal physiological conditions brain ACh levels and turnover are not regulated by the levels of free choline in plasma and that the physiologic regulatory step in ACh synthesis is the high affinity uptake of choline by cholinergic nerve endings.

Keywords

Nerve Ending Superior Cervical Ganglion Choline Uptake High Affinity Transport Choline Transport 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Ansell, G.B., and Spanner, S., 1967, The metabolism of labelled ethanolamine in brain of the rat in vivo, J. Neurochem. 14: 873.PubMedCrossRefGoogle Scholar
  2. Ansell, G.B., and Spanner, S., 1968a, The long-term metabolism of the ethanolamine moiety of rat brain myelin phospholipids, J. Neurochem. 15: 1371.PubMedCrossRefGoogle Scholar
  3. Ansell, G.B., and Spanner, S., 1968b, The metabolism of [Me-14C] choline in the brain of the rat in vivo, Biochem. J. 110: 201.PubMedGoogle Scholar
  4. Ansell, G.B., and Spanner, S., 1978, The sources of choline for acetylcholine synthesis, in “Cholinergic Mechanisms and Psychopharmacology” ( D.J. Jenden, ed.), pp. 431–445, Plenum Press, New York.Google Scholar
  5. Aquilonius, S.M., Flentge, F., Schuberth, J., Sparf, B., and Sundwall, A., 1973, Synthesis of acetylcholine in different compartments of brain nerve terminals in vivo as studied by the incorporation of choline from plasma and the effects of pentobarbital on this process, J. Neurochem. 20: 1509.PubMedCrossRefGoogle Scholar
  6. Aquilonius, S.M., Ceder, G., Lying-Tunell, U., Malmlund, H.O., and Schuberth, J., 1975, The arteriovenous difference of choline across the brain of man, Brain Res. 99: 430.PubMedCrossRefGoogle Scholar
  7. Atweh, S., and Kuhar, M.J., 1976, Effects of anesthetics and septal lesions and stimulation on 3H-acetylcholine formation in rat hippocampus, Eur. J. Pharmacol. 37: 311.PubMedCrossRefGoogle Scholar
  8. Atweh, S., Simon, J.R., and Kuhar, M.J., 1975, Utilization of sodium-dependent high affinity choline uptake in vitro as a measure of the activity of cholinergic neurons in vivo, Life Sci. 77: 1535.CrossRefGoogle Scholar
  9. Barker, L.A., 1976a, Subcellular aspects of acetylcholine synthesis, in “Biology of Cholinergic Function” ( A.M. Goldberg and I. Hanin, eds.), pp. 203–208, Raven Press, New York.Google Scholar
  10. Barker, L.A., 1976b, Modulation of synaptosomal high affinity choline transport, Life Sci. 18: 725.PubMedCrossRefGoogle Scholar
  11. Barker, L.A., (in press), The synaptosomal uptake of [3H-N-Me]-N,N,N-t rime thy 1-N-propynyl-ammonium, Fed. Proc. (Abs).Google Scholar
  12. Barker, L.A., and Mittag, T.W., 1973, Inhibition of synaptosomal choline uptake by naphthylvinylpyridiniums, FEBS Lett. 35: 141.CrossRefGoogle Scholar
  13. Barker, L.A., and Mittag, T.W., 1975, Comparative studies of substrates and inhibitors of choline transport and choline acetyltransferase, Pharmacol. Exp. Ther. 192: 86.Google Scholar
  14. Barker, L.A., and Mittag, T.W., 1976, Synaptosomal transport and acetylation of 3-trime thy laminopropan-l-o1, Biochem. Pharmacol. 25: 1931.PubMedCrossRefGoogle Scholar
  15. Barker, L.A., Dowdall, M.J., and Whittaker, V.P., 1972, Choline metabolism in the cerebral cortex of guinea pigs. Stable bound acetylcholine, Biochem. J.. 130: 1063.PubMedGoogle Scholar
  16. Barker, L.A., Dowdall, M.J., and Mittag, T.W., 1975, Comparative studies on synapto- somes: high affinity uptake and acetylation of N-[Me-3 H] choline and N-[Me-3H], N-hydroxyethylpyrrolidinium, Brain Res. 86: 343.PubMedCrossRefGoogle Scholar
  17. Barker, L.A., Mittag, T.W., and Krespan, B., 1978, Studies on substrates, inhibitors and modifiers of the high affinity choline transport-acetylation system present in rat brain synaptosomes, in “Cholinergic Mechanisms and Psychopharmacology”, ( D.J. Jenden ed.) pp. 465–480, Plenum Press, New York.Google Scholar
  18. Birks, R., and Macintosh, F.C., 1961, Acetylcholine metabolism in a sympathetic ganglion, Can. J. Biochem. Physiol 39: 787.CrossRefGoogle Scholar
  19. Bremer, I., and Greenberg, D.M., 1961, Methyl transferring enzyme system of microsomes in the biosynthesis of lecithin (phosphatidylcholine), Biochem. Biophys. Acta 46:205.CrossRefGoogle Scholar
  20. Browning, E.T., and Schulman, M.P., 1968, [14C] Acetylcholine synthesis by cortex slices of rat brain, J. Neurochem. 15: 1391.Google Scholar
  21. Burgen, A.S.W., Burke, G., and Desbarats-Schonbaum, M.L., 1956, The specificity of brain choline acetylase, Br. J. Pharmacol. 11: 308.Google Scholar
  22. Butcher, S.H., and Butcher, L.L., 1974, Acetylcholine and choline levels in the rat corpus striatum after microwave irradiation, Proc. West. Pharmacol. Soc. 17: 37.Google Scholar
  23. Butcher, S.H., Butcher, L.L., Harms, M.S., and Jenden, D.J., 1976, Fast fixation of brain in situ by high intensity microwave irradiation: application to neurochemical studies, J. Microwave Power 11: 61.Google Scholar
  24. Carrol, P.T., and Butterbaugh, G.G., 1975, Regional differences in high affinity choline transport velocity in guinea pig brain, J. Neurochem. 24: 929.Google Scholar
  25. Carrol, P.T., and Goldberg, A.H., 1975, Relative importance of choline transport to spontaneous and potassium depolarized release of acetylcholine, J. Neurochem. 25: 523.CrossRefGoogle Scholar
  26. Carson, U.G., Jenden, D.J., and Cho, A.K., 1972, The in vivo effects of some choline acetyltransferase inhibitors, Proc. West. Pharmacol. Soc. 15: 127.Google Scholar
  27. Choi, R.L., 1974, The distribution kinetics and turnover of choline and acetylcholine in plasma and brain of rats, Ph.D. Dissertation, University of California, Los Angeles (Xerox University Microfilms No. 75–9385 ).Google Scholar
  28. Choi, R.L., Freeman, J.J., and Jenden, D.J., 1975, Kinetics of plasma choline in relation to turnover of brain choline and formation of brain acetylcholine, J. Neurochem. 24: 735.PubMedGoogle Scholar
  29. Cohen, E.L., and Wurtman, R., 1975, Brain acetylcholine: increase after systemic choline administration, Life Sci. 16: 1095.PubMedCrossRefGoogle Scholar
  30. Collier, B., and Ilson, D., 1977, The effect of preganglionic nerve stimulation on the accumulation of certain analogues of choline by a sympathetic ganglion, J. Physiol. (Lond.) 264: 489.Google Scholar
  31. Collier, B., and Katz, H.S., 1974, Acetylcholine synthesis from recaptured choline by a sympathetic ganglion, J. Physiol. 238: 639.PubMedGoogle Scholar
  32. Collier, B., and Macintosh, F.C., 1969, The source of choline for acetylcholine synthesis in a sympathetic ganglion, Can. J. Physiol. Pharmacol. 47: 127.CrossRefGoogle Scholar
  33. Collier, B., Barker, L.A., and Mittag, T.W., 1976, The release of acetylated choline analogs by a sympathetic ganglion, Mol. Pharmacol. 12: 340.PubMedGoogle Scholar
  34. Collier, B., Lovat, S., Ilson, D., Barker, L.A., and Mittag, T.W., 1977, The uptake, metabolism and release of homocholine: studies with rat brain synaptosomes and cat superior cervical ganglion, J. Neurochem. 28: 331.CrossRefGoogle Scholar
  35. Currier, S.F., and Mautner, H.G., 1974, On the mechanism of action of choline acetyltransferase, Proc. Natl. Acad. Sci. USA 71: 3355.PubMedCrossRefGoogle Scholar
  36. Dauterman, W.C., and Mehrotra, K.N., 1963, The N-alkyl group specificity of choline acetylase from rat brain, J. Neurochem. 10: 113.CrossRefGoogle Scholar
  37. Diamond, I., 1971, Choline metabolism in brain, Arch. Neurol. 24: 333.PubMedGoogle Scholar
  38. Diamond, I., and Milfay, D., 1972, Uptake of [3H-methy 1] choline by microsomal, synaptosomal, mitochondrial and synaptic vesicle fractions of rat brain. The effects of hemicholinium, J. Neurochem. 79: 1899.CrossRefGoogle Scholar
  39. Dowdall, M.J., and Simon, E.J., 1973, Comparative studies on synaptosomes: uptake of [N-Me-3H] choline by synaptosomes from squid optic lobes, J. Neurochem. 21: 969.CrossRefGoogle Scholar
  40. Dowdall, M.J., and Zimmerman, H., 1977, The isolation of pure cholinergic nerve terminal sacs (T-sacs) from the electric organ of juvenile Torpedo, Neurosci. 2: 405.CrossRefGoogle Scholar
  41. Dowdall, M.J., Barker, L.A., and Whittaker, V.P., 1972, Choline metabolism in the cerebral cortex of the guinea pig: phosphorylcholine and lipid choline, Biochem. J. 130: 1081.PubMedGoogle Scholar
  42. Dross, K., 1975, Effects of diisopropylfluorophosphate on the metabolism of choline and phosphatidylcholine in rat brain, J. Neurochem. 24: 701.PubMedGoogle Scholar
  43. Dross, K., and Kewitz, H., 1972, Concentration and origin of choline in the rat brain, Naunyn Schmiedebergs Arch. Exp. Path. Pharmak. 274: 91.CrossRefGoogle Scholar
  44. Eckernas, S.A., 1977, Plasma choline and cholinergic mechanisms in the brain, Acta Physiol. Scand. (Suppl.) 449: 1.Google Scholar
  45. Fonnum, F., 1968, Choline acetyl transferase, binding to and release from membranes, Biochem. J. 109: 389.PubMedGoogle Scholar
  46. Frankenberg, L., Heimburger, G., Nilsson, C., and Sorbo, B., 1973, Biochemical and pharmacological studies on the sulfonium analogues of choline and acetylcholine, Eur. J. Pharmacol. 23: 37.PubMedCrossRefGoogle Scholar
  47. Freeman, J.J., and Jenden, D.J., 1976, The source of choline for acetylcholine synthesis in brain, Life Sci. 19: 949.PubMedCrossRefGoogle Scholar
  48. Freeman, J.J., Choi, R.L., and Jenden, D.J., 1975, Plasma choline: its turnover and exchange with brain choline, J. Neurochem. 24: 729.Google Scholar
  49. Gardiner, J.E., and Gwee, M.C.E., 1974, The distribution in the rabbit of choline administered by injection or infusion, J. Physiol. (Lond.) 239: 459.Google Scholar
  50. Gardiner, J.E., and Paton, W.D.M., 1972, The control of the plasma choline concentrations in the cat, J. Physiol (Lond.) 227: 71.Google Scholar
  51. Glick, S.D., Mittag, T.W., and Green, J.P., 1973, Central cholinergic correlates of impaired learning, Neuropharmacology 12: 291.PubMedCrossRefGoogle Scholar
  52. Glick, S.D., Crane, A.M., Barker, L.A., and Mittag, T.W., 1975, Effects of N-hydroxyethylpyrrolidinium methiodide, a choline analog, on passive avoidance behavior in mice,Neuropharmacology 14: 561.PubMedCrossRefGoogle Scholar
  53. Gray, E.G., and Whittaker, V.P., 1962, The isolation of nerve endings from brain: An electron microscopic study of the cell fragments derived by homogenization and centrifugation, J. Anat. 96: 79.PubMedGoogle Scholar
  54. Guyenet, P., Lefresne, P., Rossier, J., Beaujouan, J.C., and Glowinski, J., 1973, Inhibition by hemicholinium-3 of [14C] acetylcholine synthesis and [3H] choline high affinity uptake in rat striatal synaptosomes, Mol. Pharmacol 9: 630.PubMedGoogle Scholar
  55. Haga, T., 1971, Synthesis and release of [14C] acetylcholine in synaptosomes, J. Neurochem. 18: 781.PubMedCrossRefGoogle Scholar
  56. Haga, T., and Noda, H., 1973, Choline uptake systems of rat brain synaptosomes, Biochem. Biophys. Acta 291: 564.PubMedCrossRefGoogle Scholar
  57. Hanin, I., and Costa, E., 1976, Brain acetylcholine turnover, in “Biology of Cholinergic Function” ( A.M. Goldberg, and I. Hanin, eds.), pp. 355–377, Raven Press, New York.Google Scholar
  58. Hanin, I., and Schuberth, J., 1974, Labelling of acetylcholine in the brain of mice fed on a diet containing deuterium labelled choline: studies utilizing gas chromatography — mass spectrometry, J. Neurochem. 23: 819.CrossRefGoogle Scholar
  59. Haubrich, D.R., and Chippendale, T.J., 1976, Regulation of acetylcholine synthesis in nervous tissue, Life Sci. 20: 1465.CrossRefGoogle Scholar
  60. Haubrich, D.R., Wang, P.F.L., and Clody, D.E., 1974, Increase in tissue concentration of acetylcholine in guinea pigs in vivo induced by administration of choline, Life Sci. 14: 921.PubMedCrossRefGoogle Scholar
  61. Haubrich, D.R., Wang, P.F.L., Clody, D.E., and Wedeking, W., 1975, Increase in rat brain acetylcholine induced by choline or deanol, Life Sci. 17: 975.PubMedCrossRefGoogle Scholar
  62. Haubrich, D.R., Wang, P.F.L., Chippendale, T.J., Proctor, E., 1976, Choline and acetylcholine in rats: the effect of dietary choline, J. Neurochem. 27: 1305.CrossRefGoogle Scholar
  63. Hebb, C.O., 1972, Biosynthesis of acetylcholine in nervous tissue, Physiol. Rev. 52: 918.PubMedGoogle Scholar
  64. Hirsch, M.J., Growdon, J.H., and Wurtman, R.J., 1977, Increase in hippocampal acetylcholine after choline administration,Brain Res. 125: 383.PubMedCrossRefGoogle Scholar
  65. Illingworth, D.R., and Portman, O.W., 1972, The uptake and metabolism of plasma lysophosphatidylcholine in vivo by the brain of squirrel monkeys, Biochem. J. 130: 557.PubMedGoogle Scholar
  66. Ilson, D., and Collier, B., 1975, Triethylcholine as a precursor to a cholinergic false transmitter, Nature 254:618.PubMedCrossRefGoogle Scholar
  67. Ilson, D., Collier, B., and Boksa, P., 1977, Acetyl triethylcholine: a cholinergic false transmitter in cat superior cervical ganglion and rat cerebral cortex, J. Neurochem. 28: 371.PubMedCrossRefGoogle Scholar
  68. Jenden, D.J., Jope, R.S., and Weiler, M.H., 1976, Regulation of acetylcholine synthesis: does cytoplasmic acetylcholine control high affinity choline uptake? Science 194: 635.PubMedCrossRefGoogle Scholar
  69. Krell, R.D., and Goldberg, A.M., 1975, Effect of choline acetyltransferase inhibitors on mouse and guinea pig brain choline and acetylcholine, Biochem. Pharmacol. 24: 391.PubMedCrossRefGoogle Scholar
  70. Kuhar, M.J., and Murrin, L.C., 1978, Sodium-dependent, high affinity choline uptake, J. Neurochem. 30: 15.PubMedCrossRefGoogle Scholar
  71. Kuhar, M.J., and Simon, J.R., 1974, Acetylcholine uptake: lack of association with cholinergic neurons, J. Neurochem. 22: 1135.CrossRefGoogle Scholar
  72. Kuhar, M.J., Sethy, V.H., Roth, R.H., and Aghajanian, K.K., 1973, Choline: selective accumulation by central cholinergic neurons, J. Neurochem. 20: 581.CrossRefGoogle Scholar
  73. Lefresne, P., Guyenet, P., Beaujouan, J.C., and Glowinski, J., 1975, The subcellular localization of ACh synthesis in rat striatal synaptosomes investigated by the use of Triton X-100, J. Neurochem. 25: 415.CrossRefGoogle Scholar
  74. Mulder, A.H., Yamamura, H.I., Kuhar, M.J., and Snyder, S.H., 1974, Release of acetylcholine from hippocampal slices by potassium depolarization: dependence on high affinity choline uptake, Brain Res. 70: 372.PubMedCrossRefGoogle Scholar
  75. Murrin, L.C., and Kuhar, M.J., 1976, Activation of high-affinity choline uptake in vitro by depolarizing agents, Mol. Pharmacol. 12: 1082.PubMedGoogle Scholar
  76. Oldendorf, W.H., and Braun, L.D., 1976, [3H] Tryptamine and 3H-water as diffusible internal standards for measuring brain extraction of radio-labelled substances following carotid injection, Brain Res. 113: 219.Google Scholar
  77. Pardridge, W.M., and Oldendorf, W.H., 1977, Transport of metabolic substrates through the blood-brain barrier, J. Neurochem. 28: 5.PubMedCrossRefGoogle Scholar
  78. Pedata, F., Wieraszko, A., and Pepeu, G., 1977, Effect of choline, phosphorylcholine, and dimethylaminoethanol on brain acetylcholine level in the rat, Pharmacol. Res. Commun. 9: 755.PubMedCrossRefGoogle Scholar
  79. Polak, R.L., Molenaar, P.C., and van Gelder, M., 1977, Acetylcholine metabolism and choline uptake in cortical slices, J. Neurochem. 29:477.PubMedCrossRefGoogle Scholar
  80. Racagni, G., Trabucchi, M., and Cheney, D.L., 1975, Steady-state concentrations of choline and acetylcholine in rat brain parts during a constant rate infusion of deuterated choline, Naunyn Schmiedebergs Arch. Pharmacol 290: 99.PubMedCrossRefGoogle Scholar
  81. Saelens, J.K., Sinke, J.P., Allen, M.P., and Conroy, C.A., 1973, Some of the dynamics of choline and acetylcholine metabolism in rat brain, Arch. Int. Pharmacodyn. Ther. 203: 305.PubMedGoogle Scholar
  82. Samaras, G.M., and Contrera, J.T., 1977, Choline: high affinity uptake in vivo by rat hippocampus, J. Neurochem. 28: 1373.PubMedCrossRefGoogle Scholar
  83. Schuberth, J., and Jenden, D.J., 1975, Transport of choline from plasma to cerebrospinal fluid in the rabbit with reference to the origin of choline and to acetylcholine metabolism in brain, Brain Res. 84: 245.PubMedCrossRefGoogle Scholar
  84. Simon, J.R., and Kuhar, M.J., 1975, Impulse-flow regulation of high affinity choline uptake in brain cholinergic nerve terminals, Nature 255: 162.PubMedCrossRefGoogle Scholar
  85. Simon, J.R., and Kuhar, M.J., 1976, High affinity choline uptake: ionic and energy requirements, J. Neurochem. 27:93.Google Scholar
  86. Simon, J., Mittag, T.W., and Kuhar, M.J., 1975, Inhibition of synaptosomal uptake of choline by various choline analogs, Biochem. Pharmacol. 24: 1139.PubMedCrossRefGoogle Scholar
  87. Simon, J.R., Atweh, S., and Kuhar, M.J., 1976, Sodium dependent high affinity choline uptake: a regulatory step in the synthesis of acetylcholine, J. Neurochem. 26: 909.PubMedCrossRefGoogle Scholar
  88. Smith, J.E., Lane, J.D., Shea, P.A., and McBride, W.J., 1977, Neurochemical changes following administration of precursors of biogenic amines, Life Sci. 21: 301.PubMedCrossRefGoogle Scholar
  89. Spanner, S., Hall, R.C., and Ansell, G.B., 1976, Arterio-venous differences of choline and choline lipids across the brain of rat and rabbit, Biochem. J. 154: 133.PubMedGoogle Scholar
  90. Sparf, B., 1973, On the turnover of acetylcholine in the brain, Acta Physiol. Scand. (Suppl.) 397.Google Scholar
  91. Stavinoha, W.B., Weintraub, S.T., and Modak, A.T., 1973, The use of microwave heating to inactivate cholinesterase in rat brain prior to analysis for acetylcholine, J. Neurochem. 20: 361.PubMedCrossRefGoogle Scholar
  92. Suszkiw, J.B., and Pilar, G., 1976, Selective localization of a high affinity choline uptake system and its role in ACh formation in cholinergic nerve terminals, J. Neurochem. 26: 1133.PubMedCrossRefGoogle Scholar
  93. Tucek, S., 1970, The use of choline acetyltransferase for measuring the synthesis of acetyl-coenzyme A and its release from brain mitochondria, Biochem. J. 104: 749.Google Scholar
  94. Vaca, K., and Pilar, G., 1977, Mechanisms regulating acetylcholine synthesis at the neuromuscular junction, Soc. Neurosci. Abs. III:378, Abs. No. 1211.Google Scholar
  95. Whittaker, V.P., 1959, The isolation and characterization of acetylcholine containing particles from brain, Biochem. J. 72: 694.PubMedGoogle Scholar
  96. Whittaker, V.P., 1969, The synaptosome, in “Handbook of Neurochemistry”, Vol. II, ( A. Lajtha, ed.), pp. 327–364, Plenum Press, New York-London.Google Scholar
  97. Whittaker, V.P., Michaelson, I.A., and Kirkland, R.J.A., 1964, The separation of synaptic vesicles from nerve ending particles (synaptosomes), Biochem. J. 90: 293.PubMedGoogle Scholar
  98. Wurtman, R.J., Hirsch, M.J., and Growdon, J.H., 1977, Lecithin consumption raises serum-free-choline levels, Lancet 1: 68.CrossRefGoogle Scholar
  99. Yamamura, H.I., and Snyder, S., 1973, High affinity transport of choline into synaptosomes of rat brain, J. Neurochem. 21: 1355.CrossRefGoogle Scholar
  100. Yamamura, H.I., Kuhar, M.J., Greenberg, D., and Snyder, S., 1974, Muscarinic cholinergic receptor binding: regional distribution in monkey brain, Brain Res. 66: 541.CrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1979

Authors and Affiliations

  • L. A. Barker
    • 1
  1. 1.Department of PharmacologyMt. Sinai School of Medicine, City University of New YorkNew YorkUSA

Personalised recommendations