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Cytidine and Uridine Increase Striatal CDP-Choline Levels Without Decreasing Acetylcholine Synthesis or Release

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Summary

Aims: Treatments that increase acetylcholine release from brain slices decrease the synthesis of phosphatidylcholine by, and its levels in, the slices. We examined whether adding cytidine or uridine to the slice medium, which increases the utilization of choline to form phospholipids, also decreases acetylcholine levels and release.

Methods: We incubated rat brain slices with or without cytidine or uridine (both 25–400 μM), and with or without choline (20–40 μM), and measured the spontaneous and potassium-evoked release of acetylcholine.

Results: Striatal slices stimulated for 2 h released 2650±365 pmol of acetylcholine per mg protein when incubated without choline, or 4600±450 pmol/mg protein acetylcholine when incubated with choline (20 μM). Adding cytidine or uridine (both 25–400 μM) to the media failed to affect acetylcholine release whether or not choline was also added, even though the pyrimidines (400 μM) did enhance choline`s utilization to form CDP-choline by 89 or 61%, respectively. The pyrimidines also had no effect on acetylcholine release from hippocampal and cortical slices. Cytidine or uridine also failed to affect acetylcholine levels in striatal slices, nor choline transport into striatal synaptosomes.

Conclusion: These data show that cytidine and uridine can stimulate brain phosphatide synthesis without diminishing acetylcholine synthesis or release.

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REFERENCES

  • Ando, M., Iwata, M., Takahama, K., and Nagata, Y. (1987). Effects of extracellular choline concentrations and K+ depolarization on choline kinase and choline acetyltransferase activities in superior cervical sympathetic ganglia excised from rats. J. Neurochem. 48:1448–1453.

    Article  PubMed  CAS  Google Scholar 

  • Araki, W., and Wurtman, R. J. (1997). Control of membrane phosphatidylcholine biosynthesis by diacylglycerol levels in neuronal cells undergoing neurite outgrowth. Proc. Natl. Acad. Sci. USA 94:11946–11950.

    Article  PubMed  CAS  Google Scholar 

  • Araki, W., and Wurtman, R. J. (1998). How is membrane phospholipid biosynthesis controlled in neural tissue? J. Neurosci. Res. 51:667–674.

    Article  PubMed  CAS  Google Scholar 

  • Cansev, M., Watkins, C. J., van der Beek, E. M., and Wurtman, R. J. (2005). Oral uridine-5′-monophosphate (UMP) increases brain CDP-choline levels in gerbils. Brain Res. 1058:101–108.

    Article  PubMed  CAS  Google Scholar 

  • Choy, P. C., Paddon, D. E., and Vance, D. E. (1980). An increase in cytoplasmic CTP accelerates the reaction catalyzed by CTP:phosphocholine cytidylyltransferase in poliovirus-infected HeLa cells. J. Biol. Chem. 255:1070–1073.

    PubMed  CAS  Google Scholar 

  • Farber, S. A., Savci, V., Wei, A., Slack, B. E., and Wurtman, R. J. (1996). Choline’s phosphorylation in rat striatal slices is regulated by the activity of cholinergic neurons. Brain Res. 723:90–99.

    Article  PubMed  CAS  Google Scholar 

  • Ferguson, S. M., and Blakely, R. D. (2004). The choline transporter resurfaces: New roles for synaptic vesicles. Mol. Interv. 4:22–37.

    Article  PubMed  CAS  Google Scholar 

  • Gilberstadt, M. L., and Russell, J. A. (1984). Determination of picomole quantities of acetylcholine and choline in physiological salt solutions. Anal. Biochem. 138:78–85.

    Article  PubMed  CAS  Google Scholar 

  • Kennedy, E. P., and Weiss, S. B. (1956). The function of cytidine coenzymes in the biosynthesis of phospholipids. J. Biol. Chem. 222:193–214.

    PubMed  CAS  Google Scholar 

  • Lopez-Coviella, I., and Wurtman, R. J. (1992). Enhancement by cytidine of membrane phospholipid synthesis. J. Neurochem. 59:338–343.

    Article  Google Scholar 

  • Maire, J.-C. E., and Wurtman, R. J. (1985). Effects of electrical stimulation and choline availability on the release and contents of acetylcholine and choline in superfused slices from rat striatum. J. Physiol. (Paris) 80:189–195.

    CAS  Google Scholar 

  • Millington, W. R., and Wurtman, R. J. (1982). Choline administration elevates brain phosphorylcholine concentrations. J. Neurochem. 38:1748–1752.

    Article  PubMed  CAS  Google Scholar 

  • Richardson, U. I., Watkins, C. J., Pierre, C., Ulus, I., and Wurtman, R. J. (2003). Stimulation of CDP-choline synthesis by uridine or cytidine in PC12 rat pheochromocytoma cells. Brain Res. 971:161–167.

    Article  PubMed  CAS  Google Scholar 

  • Savci, V., and Wurtman, R. J. (1995). Effect of cytidine on membrane phospholipid synthesis in rat striatal slices. J. Neurochem. 64:378–384.

    Article  PubMed  CAS  Google Scholar 

  • Simmonds, H. A., Duley, J. A., and Davies, P. M. (1991). Analysis of purines and pyrimidines in blood, urine, and other physiological fluids. In: Hommes, F. A. (ed.), Techniques in Diagnostic Human Biochemical Genetics: A Laboratory Manual, Wiley-Liss, New York, pp. 397–424.

    Google Scholar 

  • Touchstone, J. C., Chen, L. C., and Beaver, K. M. (1980). Improved separation of phospholipids on thin layer chromatography. Lipids 15:61–62.

    CAS  Google Scholar 

  • Ulus, I. H., Wurtman, R. J., Mauron, C., and Blusztajn, J. K. (1989). Choline increases acetylcholine release and protects against the stimulation-induced decrease in phosphatide levels within membranes of rat striatum. Brain Res. 484:217–227.

    Article  PubMed  CAS  Google Scholar 

  • Ulus, I. H., Buyukuysal, R. L., and Wurtman, R. J. (1992). N-Methyl-d-aspartate increases acetylcholine release from rat striatum and cortex: Its effect is augmented by choline. J. Pharmacol. Exp. Ther. 261:1122–1128.

    PubMed  CAS  Google Scholar 

  • Wecker, L., Cawley, G., and Rothermel, S. (1989). Acute choline supplementation in vivo enhances acetylcholine synthesis in vitro when neurotransmitter release is increased by potassium. J. Neurochem. 52:568–575.

    Article  PubMed  CAS  Google Scholar 

  • Weiler, M. H., Misgeld, U., Bak, I. J., and Jenden, D. J. (1979). Acetylcholine synthesis in rat neostriatal slices. Brain Res. 176:401–406.

    Article  PubMed  CAS  Google Scholar 

  • Wurtman, R. J., Regan, M., Ulus, I., and Yu, L. (2000). Effect of oral CDP-choline on plasma choline and uridine levels in humans. Biochem. Pharmacol. 60:989–992.

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Richard J. Wurtman.

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Ulus, I.H., Watkins, C.J., Cansev, M. et al. Cytidine and Uridine Increase Striatal CDP-Choline Levels Without Decreasing Acetylcholine Synthesis or Release. Cell Mol Neurobiol 26, 561–575 (2006). https://doi.org/10.1007/s10571-006-9004-5

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