Skip to main content
Log in

Regional brain monoamines and their metabolites after portacaval shunting

  • Original Contributions
  • Published:
Metabolic Brain Disease Aims and scope Submit manuscript

Abstract

Disturbances in brain monoamine neurotransmitter metabolism have been implicated in the development of hepatic encephalopathy produced by portacaval shunting or liver disease. We have measured the content of serotonin, norepinephrine and dopamine, as well as their metabolites 5-hydroxyindoleacetic acid, dihydroxyphenylacetic acid and homovanillic acid in nine selected brain areas of rats with portacaval shunts and sham-operated control rats. All substances were measured in single samples using high performance liquid chromatography with electrochemical detection, after a simple extraction procedure. In shunted rats serotonin content was 26% higher in the raphe nuclei area, and 5-hydroxyindoleacetic acid throughout the brain (by 51 to 137%), suggesting increased serotonin turnover. Norepinephrine content was higher by 26% in the frontal cortex. Dopamine content was unaffected; however its metabolites were higher in a few areas including the caudate and ventral tegmentum. Brain content of the monoamine precursor amino acids tryptophan, tyrosine and phenylalanine was higher throughout the brain in the shunted rats. The results suggest that serotonin metabolism is altered throughout the brain after portacaval shunting, which could be related to some of the characteristic behavioral abnormalities found in this condition. Catecholamine metabolism appears to be more selectively and less extensively affected.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Alsasua, P. A., and Arias, J. (1979). Niveles de catecolaminas en distintas estructuras del cerebro de rata tras anastomosia portocava.Arch. Farmacol. Toxicol. V: 97–102.

    Google Scholar 

  • Angevine, T. B., and Cotman, C. W. (1981).Principles of Neuroanatomy, Oxford University Press, New York, pp. 314–353.

    Google Scholar 

  • Baldessarini, R. J., and Fischer, J. E. (1973). Serotonin metabolism in rat brain after surgical diversion of the portal venous circulation.Nature (London) 245: 25–27.

    Google Scholar 

  • Beaubernard, C., Salomon, F., Grange, D., Thangapregassam, M. T., and Bismuth, T. (1977). Experimental hepatic encephalopathy. Changes in the level of wakefulness in the rat with portacaval shunt.Biomedicine 27: 169–171.

    Google Scholar 

  • Bengtsson, F., Gage, F. H., Jeppsson, B., Nobin, A., and Rosengren, E. (1985). Brain monoamine metabolism and behavior in portacaval-shunted rats.Exp. Neurol. 90: 21–35.

    Google Scholar 

  • Bloch, P., Delorme, M. L., Rapin, J. R., Granger, A., Boschat, M., and Opolon, P. (1978). Reversible modifications of neurotransmitters of the brain in experimental acute hepatic coma.Surg. Gynecol. Obstet. 146: 551–558.

    Google Scholar 

  • Bradbury, M. (1979).The Concept of a Blood-Brain Barrier, John Wiley and Sons, New York, pp. 194–197, 204–209.

    Google Scholar 

  • Campbell, A., Jeppsson, B., James, J. H., Ziparo, V., and Fischer, J. E. (1984). Spontaneous motor activity increases after portacaval anastomosis in rats.Pharmacol. Biochem. Behav. 20: 875–878.

    Google Scholar 

  • Commissiong, J. W. (1985). Monoamine metabolites: Their relationship and lack of relationship to monoaminergic neuronal activity.Biochem. Pharmacol. 34: 1127–1131.

    Google Scholar 

  • Cummings, M. G., Soeters, P. B., James, J. H., Keane, J. M., and Fischer, J. E. (1976). Regional brain indoleamine metabolism following chronic portacaval anastomosis in the rats.J. Neurochem. 27: 501–509.

    Google Scholar 

  • Curzon, G. (1986). Critique. Serotonin neurochemistry revisited: A new look at some old axioms.Neurochemistry Int. 8: 155–159.

    Google Scholar 

  • Curzon, G., Kantamaneni, B. D., Fernando, J. C., Woods, M. S., and Cavanagh, J. B. (1975). Effect of chronic porta-caval anastomosis on brain tryptophan, tyrosine and 5-hydroxytryptamine.J. Neurochem. 24: 1065–1070.

    Google Scholar 

  • Deguchi, T., Sinha, A. K., and Barchas, J. D. (1973). Biosynthesis of serotonin in raphe nuclei of rat brain: Effect of p-chlorophenylalanine.J. Neurochem. 20: 1329–1336.

    Google Scholar 

  • Dodsworth, J. M., James, J. H., Cummings, M. C., and Fischer, J. E. (1974). Depletion of brain noradrenaline in acute hepatic coma.Surgery 75: 811–820.

    Google Scholar 

  • Eccleston, E. G. (1973). A method for the estimation of free and total acid-soluble plasma tryptophan using an ultrafiltration technique.Clin. Chim. Acta. 48: 269–272.

    Google Scholar 

  • Erickson, C. K. (1978). Functional relationships among central neurotransmitters. In Ehrenpreis, S., and Kopin, I. J. (eds.),Reviews of Neuroscience, Raven Press, New York, pp. 1–34.

    Google Scholar 

  • Fischer, J. E., and Baldessarini, R. J. (1971). False neurotransmitters and hepatic failure.Lancet 2: 75–79.

    Google Scholar 

  • Glowinsky, J., and Iversen, L. L. (1966). Regional studies of catecholamines in the rat brain. I.J. Neurochem. 13: 655–669.

    Google Scholar 

  • Hawkins, R. A., Mans, A. M., and Biebuyck, J. F. (1981). Regional blood-brain barrier permeability in hepatic encephalopathy.J. Cereb. Blood Flow Metab. 1: 385–386.

    Google Scholar 

  • Heffner, T. G., Hartman, J. A., and Seiden, L. S. (1980). A rapid method for the regional dissection of the rat brain.Pharmacol. Biochem. Behav. 13: 453–456.

    Google Scholar 

  • Hughes, M. J., Light, K. E., and Redington, T. (1983). Alterations in CNS amine levels by acclimitization to hypobaric hypoxia.Brain Res. Bull. 11: 255–258.

    Google Scholar 

  • Jouvet, M. (1974). Monoaminergic regulation of the sleep-waking cycle in the cat. In Schmitt, F. O., and Worden, F. G. (eds.),The Neurosciences, Third Study Program, MIT Press, Cambridge, Mass., pp. 499–508.

    Google Scholar 

  • Kuhn, D. M., Wolf, W. A., and Youdim, M. B. H. (1986). Serotonin neurochemistry revisited: A new look at some old axioms.Neurochem. Int. 8: 141–154.

    Google Scholar 

  • Kwok, R. P. S., Walls, E. K., and Juorio, A. V. (1985). The concentration of dopamine, 5-hydroxytryptamine, and some of their acid metabolites in the brain of genetically diabetic rats.Neurochem. Res. 10: 611–616.

    Google Scholar 

  • Lytie, L. D., Messing, R. B., Fisher, L., and Phebus, L. (1975). Effects of long-term corn consumption on brain serotonin and the response to electric shock.Science 190: 692–694.

    Google Scholar 

  • Mans, A. M., and Hawkins, R. A. (1986). Brain monoamines after portacaval anastomosis.Metab. Brain Dis. 1: 45–52.

    Google Scholar 

  • Mans, A. M., Biebuyck, J. F., Shelly, K., and Hawkins, R. A. (1982). Regional blood-brain barrier permeability to amino acids after portacaval anastomosis.J. Neurochem. 38: 705–717.

    Google Scholar 

  • Mans, A. M., Biebuyck, J. F., Davis, D. W., and Hawkins, R. A. (1984). Portacaval anastomosis: Brain and plasma amino acid metabolite abnormalities and the effect of nutritional therapy.J. Neurochem. 43: 697–705.

    Google Scholar 

  • Mans, A. M., Davis, D. W., Biebuyck, J. F., and Hawkins, R. A. (1986). Failure of glucose and branchedchain amino acids to normalize brain glucose use in portacaval shunted rats.J. Neurochem. 47: 1434–1443.

    Google Scholar 

  • Martin, J. R., Baettig, K., and Bircher, J. (1980). Maze patrolling, open-field behavior and runway activity following experimental portacaval anastomosis in rats.Physiol. Behav. 25: 713–719.

    Google Scholar 

  • McKay, L., Bradberry, C., and Oke, A. (1984). Ascorbic acid oxidase speeds up analysis for catecholamines, indoleamines and their metabolites in brain tissue using high-performance liquid chromatography with electrochemical detection.J. Chromatogr. 311: 167–169.

    Google Scholar 

  • Munro, H. N., Fernstrom, J. D., and Wurtman, R. J. (1975). Insulin, plasma amino acid imbalance and hepatic coma.Lancet 1: 722–724.

    Google Scholar 

  • Reinhard, J. F., and Wurtman, R. J. (1977). Relation between brain 5-HIAA levels and release of serotonin into brain synapses.Life Sci. 21: 1741–1746.

    Google Scholar 

  • Reinstein, D. K., Lehnert, H., Scott, N. A., and Wurtman, R. J. (1984). Tyrosine prevents behavioral and neurochemical correlates of an acute stress in rats.Life Sci. 34: 2225–2231.

    Google Scholar 

  • Sarna, G. S., Bradbury, M. W. B., Cremer, J. E., Lai, J. C. V., and Teal, H. M. (1979). Brain metabolism and specific transport at the blood-brain barrier after portacaval anastomosis in the rat.Brain Res. 160: 69–83.

    Google Scholar 

  • Simert, G., Nobin, A., Rosengren, E., and Vang, J. (1978). Neurotransmitter changes in the rat brain after portacaval anastomosis.Eur. Surg. Res. 10: 73–85.

    Google Scholar 

  • Tenen, S. S. (1967). The effects of p-chlorophenylalanine, a serotonin depletor, on avoidance acquisition, pain sensitivity, and related behaviors in the rat.Psychopharmacology 10: 204–219.

    Google Scholar 

  • Yuwiler, A., Bennett, B. L., and Geller, E. (1982). Is there a probeneoid sensitive transport system for monoamine catabolites at the level of the brain capillary plexus?Neurochem. Res.7: 1277–1285.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mans, A.M., Consevage, M.W., DeJoseph, M.R. et al. Regional brain monoamines and their metabolites after portacaval shunting. Metabolic Brain Disease 2, 183–193 (1987). https://doi.org/10.1007/BF00999609

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00999609

Key words

Navigation