Ontogenesis of Tryptophan Transport in the Rat Brain

  • M. Hamon
  • S. Bourgoin
Conference paper
Part of the Journal of Neural Transmission book series (NEURAL SUPPL, volume 15)


During the first three postnatal weeks, the levels of tryptophan in the brain are exceptionally high, 2–4 times those found in adult rats. This is related to two main peculiarities concerning tryptophan transport in young animals: 1. the lack of tryptophan binding onto serum albumin which makes its diffusion from plasma to tissues easier for the early life period; 2. the greater capacity of synaptosomes from neonates to accumulate tryptophan.

Experiments consisting of electrolytic lesioning of the midbrain raphé or 5, 7-dihydroxytryptamine treatment clearly demonstrate that the uptake of tryptophan during postnatal development is not more active in serotoninergic than in other types of nerve terminals.

In adult rats, changing the concentration of tryptophan induces parallel modifications in the rate of 5-HT synthesis in the brain since the rate limiting enzyme, tryptophan hydroxylase, is not saturated by its substrate. In contrast, neither tryptophan loading, nor parachlorophenylalanine administration (resulting in a marked decrease in brain tryptophan levels) alters the rate of 5-HT synthesis in the CNS of neonates, indicating that tryptophan hydroxylase is saturated during the early life period. These results are discussed in relation to the possible non-transmitter role of 5-HT during brain growth.


Tryptophan Hydroxylase Electrolytic Lesion Tryptophan Level Free Tryptophan Amino Acid Carrier 
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.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Baker, P. C, Quay, W. B.: 5-Hydroxytryptamine metabolism in early embryogenesis and the development of brain and retinal tissues. A review. Brain Res. 12, 273–295 (1969).CrossRefGoogle Scholar
  2. Barondes, S. H.: Do tryptophan concentrations limit protein synthesis at specific sites in the brain? In: Aromatic amino acids in the brain, Ciba Found. Symp. (Wolstenholme, G. E., Fitzsimons, D. W., eds.), 22, pp. 265–274. Amsterdam-London-New York: Elsevier, Excerpta Medica, North Holland. 1974.Google Scholar
  3. Bauman, A., Bourgoin, S., Benda, P., Glowinski, J., Hamon, M.: Characteristics of tryptophan accumulation by glial cells. Brain Res. 66, 253–263 (1974).CrossRefGoogle Scholar
  4. Bourgoin, S.: Evolution du métabolisme cerebral de la sérotonine chez le rat au cours du développement. Thèse de Doctorat ès Sciences Naturelles, Université de Paris VII, 1-303 (1976).Google Scholar
  5. Bourgoin, S., Enjalbert, A., Adrien, J., Héry, F., Hamon, M.: Midbrain raphe lesion in the new born rat: II. Biochemical alterations in serotoninergic innervation. Brain Res. 127, 111–126 (1977 a).CrossRefGoogle Scholar
  6. Bourgoin, S., Faivre-Bauman, A., Benda, P., Glowinski, J., Hamon, M.: Plasma tryptophan and 5-HT metabolism in the CNS of the new born rat. J. Neurochem. 23, 319–327 (1974).PubMedCrossRefGoogle Scholar
  7. Bourgoin, S., Faivre-Bauman, A., Héry, F., Ternaux, J. P., Hamon, M.: Characteristics of tryptophan binding in the serum of the new born rat. Biol. Neonate 31, 141–154 (1977 b).PubMedCrossRefGoogle Scholar
  8. Chanez-Bel, C.: Retard de croissance intrautérine chez le rat. Thèse, Paris VI, 1972.Google Scholar
  9. Curzon, G., Knott, P. J.: Environmental, toxicological and related aspects of tryptophan metabolism with particular reference to the central nervous system. CRC Critical Rev. Toxicol. 1977, 145-187.Google Scholar
  10. De Montis, M. G., Olianas, M. C, Mulas, G., Tagliamonte, A.: Evidence that only free serum tryptophan exchanges with the brain. Pharmacol. Res. Comm. 9, 215–220 (1977).CrossRefGoogle Scholar
  11. Denizeau, F., Sourkes, T. L.: Regional transport of tryptophan in rat brain. J. Neurodiem. 28, 951–959 (1977).Google Scholar
  12. Etienne, P., Young, S. N., Sourkes, T. L.: Inhibition by albumin of tryptophan uptake by brain. Nature 262, 144–145 (1976).PubMedCrossRefGoogle Scholar
  13. Fernstrom, J. D., Wurtman, R. J.: Brain serotonin content: physiological regulation by plasma neutral amino acids. Science 178, 414–416 (1972).PubMedCrossRefGoogle Scholar
  14. Gessa, G. L., Tagliamonte, A.: Serum free tryptophan: control of brain concentrations of tryptophan and of synthesis of 5-hydroxytryptamine. In: Aromatic amino acids in the brain, Ciba Found. Symp. (Wolstenholme, G. E., Fitzsimons, D. W., eds.), 22, pp. 207–216. Amsterdam-London-New York: Elsevier, Excerpta Medica, North Holland. 1974.Google Scholar
  15. Hamon, M., Bourgoin, S., Morot-Gaudry, Y., Héry, F., Glowinski, J.: Role of active transport of tryptophan in the control of 5-hydroxytryptamine biosynthesis. In: Advances in Biochemical Psychopharmacology Costa, E., Gessa, G. L., Sandler, M., eds.), 11, pp. 153–162. New York: Raven Press. 1Google Scholar
  16. Hamon, M., Glowinski, J.: Regulation of serotonin synthesis. Life Sci. 15, 1533–1548 (1974).PubMedCrossRefGoogle Scholar
  17. Hoff, K. M., Baker, P. C., Buda, R.: Free tryptophan levels in regions of the maturing mouse brain. Brain Res. 73, 376–379 (1974).PubMedCrossRefGoogle Scholar
  18. Hoff, K. M., Baker, P. C., Buda, R. E.: Precursor and end product effects upon indoleamine maturation in mouse brain. Biol. Neonate 29, 360–367 (1976).PubMedCrossRefGoogle Scholar
  19. Hoff, K. M., Baker, P. C, Buda, R. E.: Effects of parachlorophenylalanine on indoleamines in maturing mouse brain. Gen. Pharmacol. 8, 213–215 (1977).PubMedCrossRefGoogle Scholar
  20. Hole, K.: Reduced 5-hydroxyindole synthesis reduces postnatal brain growth in rats. Eur. J. Pharmacol. 18, 361–366 (1972).PubMedCrossRefGoogle Scholar
  21. Knott, P. J., Joseph, M. H., Curzon, G.: Effects of food deprivation and immobilization on tryptophan and other amino acids in the rat brain. J. Neurochem. 20, 249–251 (1973).PubMedCrossRefGoogle Scholar
  22. Korpi, E. R., Oja, S. S.: Tryptophan influx into rat brain slices in different buffers and in the presence of other amino acids and albumin. J. Neurochem. 30, 925–927 (1978).PubMedCrossRefGoogle Scholar
  23. Kuhar, M. J., Aghajanian, G. K.: Selective accumulation of 3H-serotonin by nerve terminals of raphe neurons: an autoradiographic study. Nature (New Biol.) 241, 187–189 (1973).Google Scholar
  24. Miller, M., Leahy, J.P., Stern, W.C., Morgane, P. J., Resnick, O.: Tryptophan availability: relation to elevated brain serotonin in developmentally protein-malnourished rats. Exp. Neurol. 57, 142–157 (1977).PubMedCrossRefGoogle Scholar
  25. Pérez-Cruet, J., Chase, T. N., Murphy, D. L.: Dietary regulation of brain tryptophan metabolism by plasma ratio of free tryptophan and neutral amino acids in humans. Nature 248, 693–695 (1974).PubMedCrossRefGoogle Scholar
  26. Sidransky, H., Sarma, D. S. R., Bongiorno, M., Verney, E.: Effect of dietary tryptophan on hepatic polyribosomes and protein synthesis in fasted mice. J. Biol. Chem. 243, 1123–1132 (1968).PubMedGoogle Scholar
  27. Tyce, G. M., Flock, E. V., Owen, C. A., jr.: Tryptophan metabolism in the brain of the developing rat. In: Progress in Brain Research (Himwich, W. A., Himwich, H. E., eds.), 9, pp. 198–203. Amsterdam: Elsevier. 1964.Google Scholar
  28. Wigglesworth, J. S.: Experimental growth retardation in the fetal rat. J. Path. Bact. 88, 1 (1964).PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Wien 1979

Authors and Affiliations

  • M. Hamon
    • 1
  • S. Bourgoin
    • 1
  1. 1.Groupe NB-INSERM U 114Collège de FranceParis Cedex 05France

Personalised recommendations