Journal of Inherited Metabolic Disease

, Volume 11, Issue 3, pp 285–290

Serotonin and noradrenaline concentrations and serotonin uptake in platelets from hyperphenylalaninaemic patients

  • M. Giovannini
  • R. Valsasina
  • R. Longhi
  • A. M. Cesura
  • M. D. Galva
  • E. Riva
  • G. P. Bondiolotti
  • G. B. Picotti
Article

Summary

In three untreated patients with phenylketonuria (PKU), three PKU and six hyperphenylalaninaemic (HPA) patients in good metabolic control, the kinetic constants of plateletin vitro uptake of [14C]serotonin (5HT) did not significantly differ from those in 12 control subjects matched for age. The platelet concentrations of endogenous 5HT and noradrenaline (NA), taken as long-term indices of the amount of these amines circulating in plasma, were lower than normal in PKU and HPA patients, whether or not they were kept on a diet. However, a reduction in plasma NA concentrations at the moment of blood collection was seen only in untreated PKU patients. These data indicate that there may be a chronic inhibition of 5HT and possibly of NA synthesis even in PKU or HPA subjects in good metabolic control, with normal psychomotor development and only slightly raised plasma phenylalanine levels.

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References

  1. Bondiolotti, G. P., Galva, M. D. and Picotti, G. B. Simultaneous determination of catecholamines,l-dopa and DOPAC in human plasma by high-performance liquid chromatography with electrochemical detection. 6th Int. Catecholamine Symposium, Jerusalem, abstr. (1987) p. 116Google Scholar
  2. Bondiolotti, G. P., Picotti, G. B., Galva, M. D., Cesura, A. M. and Da Prada, M. Stress-induced changes in platelet catecholamine concentrations in rats. In Usdin, E., Kvetnansky, R. and Axelrod, J. (eds.)Stress: The Role of Catecholamines and Other Neurotransmitters, Gordon & Breach, New York, 1984, pp. 577–586Google Scholar
  3. Buhler, H. U., Da Prada, M., Haefely, W. and Picotti, G. B. Plasma adrenaline, noradrenaline and dopamine in man and different animal species.J. Physiol. 276 (1978) 311–320Google Scholar
  4. Butler, I. J., O'Flinn, M. E., Seifert, W. E. and Rodney Howell, R. Neurotransmitter defect and treatment of disorders of hyperphenylalaninemia.J. Pediatr. 98 (1981) 729–733Google Scholar
  5. Buus-Lassen, J. Potent and long-lasting potentiation of two 5-hydroxytryptophan-induced effects in mice by three selective 5-HT uptake inhibitors.Eur. J. Pharmacol. 47 (1978) 352–358Google Scholar
  6. Curtius, H. C., Wiederwieser, A., Viscontini, M., Leimbacher, W., Wegman, H., Blehova, B., Rey, F., Schaut, J. and Schmidt, H. Serotonin and dopamine synthesis in phenylketonuria.Adv. Exp. Med. Biol. 133 (1981) 277–291Google Scholar
  7. Da Prada, M. and Picotti, G. B. Content and subcellular localization of catecholamines and 5-hydroxytryptamine in human and animal blood platelets: monoamine distribution between platelets and plasma.Br. J. Pharmacol. 65 (1979) 653–662Google Scholar
  8. Guttler, F. Hyperphenylalaninemia: diagnosis and classification of the various types of phenylalanine hydroxylase deficiency in childhood.Acta Pediatr. Scand. Supp. 280 (1980) 1–80Google Scholar
  9. Guttler, F. and Lou, H. Dietary problems of phenylketonuria: effect on CNS transmitters and their possible role in behaviour and neuropsychological function.J. Inher. Metab. Dis. 9 Suppl. 2 (1986) 169–177Google Scholar
  10. Herrero, E., Aragon, M. C., Gimenez, C. and Valdivieso, E. Inhibition byl-phenylalanine of tryptophan transport by synaptosomal plasma membrane vesicles: implications in the pathogenesis of phenylketonuria.J. Inher. Metab. Dis. 6 (1983) 32–35Google Scholar
  11. Hommes, F. A. Myelin turnover at later stages of brain development in experimental hyperphenylalaninemia. In Bickel, H. and Wachtel, U. (eds.)Inherited Disease of Amino Acid Metabolism. Georg Thieme Verlag, New York, 1985, pp. 67–85Google Scholar
  12. Lowry, O. H., Rosenbrough, N. J., Farr, A. L. and Randall, R. J. Protein measurements with the Folin phenol reagent.J. Biol. Chem. 193 (1951) 265–275Google Scholar
  13. Malmgren, R. Platelets and biogenic amines. Indications for a discrete low affinity uptake mechanism shared by norepinephrine and 5-hydroxytryptamine in human platelets.Psychopharmacology 90 (1986) 384–389Google Scholar
  14. McKean, C. M. The effect of high phenylalanine concentrations on serotonin and catecholamine metabolism in the human brain.Brain Res. 47 (1972) 469–476Google Scholar
  15. McKean, C. M., Boggs, D. E. and Peterson, N. A. The influence of high phenylalanine and tyrosine on the concentration of essential amino acids in brain.J. Neurochem. 15 (1968) 235–241Google Scholar
  16. Pare, C. M. B., Sandler, M. and Stacey, R. S. 5-hydroxytryptamine deficiency in phenylketonuria.Lancet 2 (1958) 1099–1101Google Scholar
  17. Picotti, G. B., Bondiolotti, G. P., Cesura, A. M., Ravazzani, C., Galva, M. D. and Mantegazza, P. Free (unconjugated) catecholamine concentrations in platelets: biological significance and clinical implications. In Strano, A. (ed.)Thrombosis and Cardiovascular Diseases. Plenum Press, New York, 1984, pp. 257–268Google Scholar
  18. Picotti, G. B., Carruba, M. O., Zambotti, F. and Mantegazza, P. Effects of mazindol and fenfluramine on 5-hydroxytryptamine uptake, storage and metabolism in blood platelets.Eur. J. Pharmacol. 42 (1977) 217–224Google Scholar
  19. Pletscher, A. Platelets as models for monoaminergic neurons. In Youdim, M. B. H., Lovenberg, W., Sharman, D. F. and Lagnado, J. R. (eds.)Essay in Neurochemistry and Neuropharmacology. John Wiley and Sons, Chichester, 1978, pp. 49–101Google Scholar
  20. Sandler, M. Inborn errors and disturbances of central neurotransmission (with special reference to phenylketonuria).J. Inher. Metab. Dis. 5 Suppl. 2 (1982) 65–70Google Scholar

Copyright information

© SSIEM and MTP Press Limited 1988

Authors and Affiliations

  • M. Giovannini
    • 1
  • R. Valsasina
    • 1
  • R. Longhi
    • 1
  • A. M. Cesura
    • 2
  • M. D. Galva
    • 2
  • E. Riva
    • 1
  • G. P. Bondiolotti
    • 2
  • G. B. Picotti
    • 3
  1. 1.5th Pediatric DepartmentUniversity ofMilan
  2. 2.Department of PharmacologyUniversity ofMilan
  3. 3.Institute of PharmacologyUniversity of GenoaItaly
  4. 4.5th Pediatric Department, Institute of Biomedical SciencesSan Paolo HospitalMilanoItaly

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