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Regulation of Choline Phosphorylation in Rat Striatum

  • R. R. Reinhardt
  • L. Wecker

Abstract

In cholinergic nerve terminals, choline is an important precursor molecule for the synthesis of both acetylcholine (ACh) and phosphorylcholine (PCh) through reactions catalyzed by choline acetyltransferase (CAT) and choline kinase (CK), respectively. While studies have indicated that CAT exists in both soluble and membrane associated forms which may subserve different primary functions in the nerve terminal (Smith and Carroll, 1980; Benishin and Carroll, 1983), little similar information has been available for CK. This enzyme catalyzes the first and possibly rate-limiting step (infante, 1977) in the cytidine pathway (Kennedy and Weiss, 1956) which is the major pathway for the incorporation of choline into phosphatidylcholine in brain (Ansell and Spanner, 1968). Since choline serves as a substrate for both CAT and CK, it might be expected that the nerve terminal has regulatory mechanisms to channel choline through the pathway that requires the precursor most at any given instant. Indeed, an association between the acetylation and phosphorylation pathways has been suggested (Ansell and Spanner, 1970; Collier, 1970). Therefore, to further our understanding of the utilization of choline by the cholinergic neuron, we studied the properties of CK and the modulation of choline phosphorylation by endogenous agents.

Keywords

Cholinergic Neuron Choline Uptake Total Enzyme Activity Choline Kinase 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.

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References

  1. Ansell, G.B. and Spanner, S. (1968) The metabolism of ( Me-C) choline in the brain of the rat in vivo, Biochem. J., 110: 201–206.PubMedGoogle Scholar
  2. Ansell, G.B. and Spanner, S. (1970) The origin and turnover of choline in the brain, in: Drugs and Cholinergic Mechanisms in the CNS, E. Heilbronn and A. Winter, eds., Forsvarets Forskningsanstalt, Stockholm, Sweden, pp. 143–159.Google Scholar
  3. Barker, L.A. and Mittag, T. (1975) Comparative studies of substrates and inhibitors of choline transport and choline acetyltransferase, J. Pharmacol. Exp. Ther., 192: 86–94.Google Scholar
  4. Benishin, C.G. and Carroll, P.T. (1983) Multiple forms of choline-acetyltransferase in mouse and rat brain: Solubilization and characterization, J. Neurochem., 41: 1030–1039.Google Scholar
  5. Bygrave, F.L. and Dawson, R.M.C. (1976) Phosphatidylcholine biosynthesis and choline transport in the anaerobic protozoon Entodinium caudatum, Biochem. J., 160: 481–490.Google Scholar
  6. Collier, B. (1970) Biosynthesis of acetylcholine in vitro and in vivo, in: Drugs and Cholinergic Mechanisms in the CNS, E. Heilbronn and A. Winter, eds., Forsvarets Forskningsanstalt, Stockholm, Sweden, pp. 163–172.Google Scholar
  7. Cook, P.F., Neville, M.E.,Jr., lrana, K.E., Hartl, T. and Roskoski,R., Jr., (1982) Adenosine cyclic 31, monophosphate dependent protein kinase: Kinetic mechanism for the bovine skeletal muscle catalytic subunit, Biochem., 21: 5794–5799.Google Scholar
  8. Daly, J. (1982) Adenosine receptors: Targets for future drugs, J. Med. Chem., 25: 197–207.Google Scholar
  9. Dowdle, E.B. and Maske, R. (1980) The effects of calcium concentration on the inhibition of cholinergic neurotransmission in the myenteric plexus of guinea-pig ileum by adenine nucleotides, Brit. J. Pharmacol., 71: 245–252.Google Scholar
  10. Harms, H.H., Wardeh, G. and Mulder, A.H. (1979) Effects of adenosine on depolarization-induced release of various radiolabelled neurotransmitters from slices of rat corpus striatum, Neuropharmacol., 18: 577–580.CrossRefGoogle Scholar
  11. Haubrich, D.R., Williams, M., Yarbrough, G.G. and Wood, P.L. (1981) 2- Chloroadenosine inhibits brain acetylcholine turnover in vivo, Can. J. Physiol. Pharmacol., 59: 1196–1198.Google Scholar
  12. Infante, J.P. (1977) Rate-limiting steps in the cytidine pathway for the synthesis of phosphatidylcholine and phosphatidylethanolamine, Biochem. J., 167: 847–849.Google Scholar
  13. Jackisch, R., Strittmatter, H., Kasakov, L. and Hertting, G. (1984) Endogenous adenosine as a modulator of hippocampal acetylcholine release. Naunyn-5chmiedeberqTs Arch. Pharmacol., 327: 319–325.Google Scholar
  14. Kennedy, E.P. and Weiss, S.B. (1956) The function of cytidine coenzymes in the biosynthesis of phospholipids, J. Biol. Chem., 222: 193–214.Google Scholar
  15. Kuhar, M.J. and Murrin, L.C. (1978) Sodium-dependent high affinity choline uptake, J. Neurochem., 30: 15–21.PubMedCrossRefGoogle Scholar
  16. Massarelli, R. and Wong, T.Y. (1981) Choline uptake in nerve cultures and in synaptosomal preparation is regulated by the endogenous pool of choline, in: Cholinergic Mechanisms. Pepeu, G. and Ladinsky, H., eds., Vol. 25, Plenum Press, New York, pp. 511–520.Google Scholar
  17. McCaman, R.E. and Cook, K. (1966) Intermediary metabolism of phospholipids in brain tissue. III. Phosphocholine-glyceride transferase, J. Biol. Chem., 241: 3390–3394.Google Scholar
  18. Meyer, E.M., Jr., Engel, D.A. and Cooper, J.R. (1982) Acetylation and phosphorylation of choline following high or low affinity uptake by rat cortical synaptosomes, Neurochem. Res., 7: 749–759.Google Scholar
  19. Millington, UJR and Ulurtman, R.J, (1982) Choline administration elevates brain phosphorylcholine concentrations, J. Neurochem, 38: 1748–1752.PubMedCrossRefGoogle Scholar
  20. Murray, T.F., Blaker, UJ.D., Cheney, D.L. and Costa, E. (1982) Inhibition of acetylcholine turnover rate in rat hippocampus and cortex by intraventricular injection of adenosine analogs, J. Pharmacol. Exp. Ther., 222: 550–554.Google Scholar
  21. Pedata, F., Antonelli, T., Lambertini, L., Beani, L. and Pepeu, G. (1983) Effect of adenosine, adenosine triphosphate, adenosine deaminase, dipyridamole and aminophylline on acetylcholine release from electrically-stimulated brain slices, Neuropharmacol., 22: 609–614.CrossRefGoogle Scholar
  22. Reinhardt, R.R. and Uecker, L. (1983) Evidence for membrane-associated choline kinase activity in rat striatum, J. Neurochem., 41: 623–629.PubMedCrossRefGoogle Scholar
  23. Reinhardt, R.R., Ujecker, L. and Cook, P.F. (1984) Kinetic mechanism of choline kinase from rat striata, J. Biol. Chem., 259: 7446–7452.PubMedGoogle Scholar
  24. Schmidt, D.E. and iiiecker, L. (1981) CNS effects of choline administration: Evidence for temporal dependence, Neuropharmacol., 20: 535–539.Google Scholar
  25. Smith, C.P. and Carroll, P.T. (1980) A comparison of solubilized and membrane-bound forms of choline-O-acetyltransferase (EC 2.3.1.6) in mouse brain nerve endings, Brain Research, 185: 363–371.PubMedCrossRefGoogle Scholar
  26. Spanner, S. and Ansell, G.B. (1978) Choline and ethanolamine kinase activity in the cytoplasm of nerve endings from rat forebrain, Adv. Exp. Med. Biol., 101: 237–245.Google Scholar
  27. Spanner, S. and Ansell, G.B. (1979) Choline kinase and ethanolamine kinase activity in the cytosol of nerve endings from rat forebrain, Biochem. J., 178: 753–760.Google Scholar
  28. Stone, T.UJ (1981) Physiological roles for adenosine and adenosine 5-triphosphate in the nervous system, Neurosci., 6: 523–555.CrossRefGoogle Scholar
  29. Upreti, R.K., Sanual, G.G. and Krishnan, P.S. (1976) Likely individuality of the enzymes catalyzing the phosphorylation of choline and ethanolamine, Arch. Biochem. Biophys., 174: 658–665.Google Scholar
  30. Yavin, E. (1976) Regulation of phospholipid metabolism in differentiating cells from rat brain cerebral hemispheres in culture: Patterns of acetylcholine, phosphocholine and choline phosphoglycerides labeling from (methyl- C)choline, J. Biol. Chem., 25: 1392–1397.Google Scholar

Copyright information

© Plenum Press, New York 1987

Authors and Affiliations

  • R. R. Reinhardt
    • 1
  • L. Wecker
    • 1
  1. 1.Department of PharmacologyLouisiana State University Medical CenterNew OrleansUSA

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