Advertisement

Molecular and Cellular Biochemistry

, Volume 267, Issue 1–2, pp 39–46 | Cite as

Effect of orally administered l-tryptophan on serotonin, melatonin, and the innate immune response in the rat

  • Susana Esteban
  • Cristina Nicolaus
  • Antonio Garmundi
  • Rubén Victor Rial
  • Ana Beatriz Rodríguez
  • Eduardo Ortega
  • Carmen Barriga Ibars
Article

Abstract

To assess the effects of external administration of L-tryptophan on the synthesis of serotonin and melatonin as well as on the immune function of Wistar rats, 300 mg of the amino acid were administered through an oral cannula either during daylight (08:00) or at night (20:00) for 5 days. Brain, plasma, and peritoneal macrophage samples were collected 4 h after the administration. The accumulation of 5-hydroxytryptophan (5-HTP) after decarboxylase inhibition was used to measure the rate of tryptophan hydroxylation in vivo. Circulating melatonin levels were determined by radioimmunoassay, and the phagocytic activity of macrophages was measured by counting, under oil-immersion phase-contrast microscopy, the number of particles ingested. The results showed a diurnal increase (p < 0.05) in the brain 5-HTP, serotonin (5-hydroxytryptamine, 5-HT), and 5-hydroxyindolacetic acid (5-HIAA) of the animals which had received tryptophan at 08:00 and were killed 4 h later. In the animals which received tryptophan during the dark period, the 5-HT declined but the 5-HT/5-HIAA ratio remained unchanged. There was also a significant increase (p < 0.05) in nocturnal circulating melatonin levels and in the innate immune response of the peritoneal macrophages in the animals which had received tryptophan at 20:00. The results indicated that the synthesis of serotonin and melatonin, as well as the innate immune response, can be modulated by oral ingestion of tryptophan. (Mol Cell Biochem 267: 39–46, 2004)

tryptophan serotonin 5-HT serotonin synthesis melatonin phagocytosis macrophages 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Sugden D: Melatonin biosynthesis in the mammalian pineal gland. Experientia 45: 922–932, 1989PubMedGoogle Scholar
  2. 2.
    Reiter RJ: Neuroendocrine effects of light. Int J Biometeorol 35: 169–175, 1991PubMedGoogle Scholar
  3. 3.
    Klein DC, Coon SL, Roseboom PH, Weller JL, Bernard M, Gastel JA, Zatz M, Iuvone PM, Rodriguez IR, Begay V, Falcon J, Cahill GM, Cassone V, Baler R: The melatonin rhythm-generating enzyme: Molecular regulation of serotonin N-acetyltransferase in the pineal gland. Recent Prog Horm Res 52: 307–358, 1997PubMedGoogle Scholar
  4. 4.
    Wehr TA: Melatonin and seasonal rhythms. J Biol Rhythms 12: 518–527, 1997PubMedGoogle Scholar
  5. 5.
    Huether G: The contribution of extrapineal sites of melatonin synthesis to circulating melatonin levels in higher vertebrates. Experientia 49: 665–670, 1993PubMedGoogle Scholar
  6. 6.
    Roseboom PH, Coon SL, Baler R, McCune SK, Weller JL, Klein DC: Melatonin synthesis: Analysis of the more than 150-fold nocturnal increase in serotonin N-acetyltransferase messenger ribonucleic acid in the rat pineal gland. Endocrinology 137: 3033–3044, 1996PubMedGoogle Scholar
  7. 7.
    Huether G, Poeggeler B, Adler L, Ruther E: Effects of indirectly acting 5-HT receptor agonists on circulating melatonin levels in rats. Eur J Pharmacol 238: 249–255, 1993PubMedGoogle Scholar
  8. 8.
    Sugden D: 5-Hydroxytryptamine amplifies ß adrenergic stimulation of N-acetyltransferase activity in rat pinealocytes. J Neurochem 55: 1655–1658, 1990PubMedGoogle Scholar
  9. 9.
    Miguez JM, Simonneaux V, Pevet P: Evidence for regulatory role of melatonin on serotonin release and uptake in the pineal gland. J Neuroendocrinol 7: 949–956, 1995PubMedGoogle Scholar
  10. 10.
    Miguez JM, Simonneaux V, Pevet P: The role of the intracellular and extracellular serotonin in the regulation of melatonin production in rat pinealocytes. J Pineal Res 23: 63–71, 1997PubMedGoogle Scholar
  11. 11.
    Steardo L, Monteleone P, Trabace L, Cannizzaro C, Maj M, Cuomo V: Serotonergic modulation of rat pineal gland activity: in vivo evidence for hydroxytryptamine (2C) receptor involvement. J Pharmacol Exp Ther 295: 266–273, 2000PubMedGoogle Scholar
  12. 12.
    Cavallo A, Richards GE, Meyer WJ, Waldrop RD: Evaluation of 5-hydroxytryptophan administration as a test of pineal function in humans. Horm Res 27: 69–73, 1987.PubMedGoogle Scholar
  13. 13.
    Rodríguez AB, Marchena JM, Nogales G, Durhán J, Barriga C: Correlation between circadian rhythm of melatonin and the phagocytosis and superoxide anion levels in ring dove heterophils. J Pineal Res 26: 35–42, 1999PubMedGoogle Scholar
  14. 14.
    Rodríguez AB, Terrón MP, Durán J, Ortega E, Barriga C: Physiological concentrations of melatonin and corticosterone effect phagocytosis and oxidative metabolism of ring dove heterophils. J Pineal Res 31: 31–38, 2001PubMedGoogle Scholar
  15. 15.
    Skwarlo-Sonta K: Melatonin in immunity: Comparative aspects. Neuroendocrin Lett 23: 61–66, 2002Google Scholar
  16. 16.
    Reiter RJ, Tan DX, Qi W, Manchester LC, Karbownik M, Calvo JR: Pharmacology and physiology of melatonin in the reduction of oxidative stress in vivo. Biol Signals Recept 9: 160–171, 2000PubMedGoogle Scholar
  17. 17.
    Barriga C, Martín MI, Tabla R, Ortega E, Rodríguez AB: Circadian rhythm of melatonin, corticosterone and phagocytosis: Effect of stress. J Pineal Res 30: 180–187, 2001PubMedGoogle Scholar
  18. 18.
    Karlsson A, Davis JN, Kehr W, Lindqvist M, Atack CV: Simultaneous measurement of tyrosine and tryptophan hydroxylase activities in brain in vivo using an inhibitor of the aromatic amino acid decar-boxylase. Naunyn-Schmiedeberg's Arch Pharmacol 275: 153–168, 1972Google Scholar
  19. 19.
    Nissbrandt H, Engberg G, Wikstrom H, Magnusson T, Carlsson A: NSD 1034: An amino acid decarboxylase inhibitor with a stimulatory action on dopamine synthesis not mediated by classical dopamine receptors. Arch Pharmacol 338: 148–161, 1988Google Scholar
  20. 20.
    Sastre-Coll A, Esteban S, Garcia-Sevilla JA: Effects of imidazoline receptor ligands on monoamine synthesis in the rat brain in vivo. Arch Pharmacol 360: 50–62, 1999Google Scholar
  21. 21.
    Ortega E, Rodríguez AB, Barriga C, Forner MA: Corticosterone, prolactin and thyroid hormones as mediators of stimulated phagocytic capacity of peritoneal macrophages after high-intensity exercise. Int J Sports Med 17: 149–155, 1996PubMedGoogle Scholar
  22. 22.
    Wurtman RJ, Hefti F, Melamed E: Precursor control of neurotransmitter synthesis. Pharmacol Rev 32: 315–335, 1980PubMedGoogle Scholar
  23. 23.
    Hajak G, Huether G, Blanke J, Blomer M, Freyer C, Poeggeler B, Reimer A, Rodenbeck A: The influence of intravenous L-tryptophan on plasma melatonin and sleep in men. Pharmacopsychiatry 244: 17–20, 1991Google Scholar
  24. 24.
    Miguez JM, Martin FJ, Aldegunde M: Melatonin effects on serotonin synthesis and metabolism in the striatum, nucleus accumbens, and dorsal and median raphe nucleus of rats. Neurochem Res 22: 87–92, 1977Google Scholar
  25. 25.
    Sun X, Deng J, Liu T, Borjigin J: Circadian 5-HT production regulated by adrenergic signaling. Neurobiology 99: 4686–4691, 2002Google Scholar
  26. 26.
    Falcón J: Cellular circadian clocks in the pineal: Prog Neurobiol 58: 121–162, 1999PubMedGoogle Scholar
  27. 27.
    Brzozowski T, Konturek P, Konturek S, Pajdon R, Bielanski W, Brzo-zowka I, Stachura J, Hahn E: The role of melatonin and L-tryptophan in prevention of acute gastric lesions induced by stress, ethanol, ischemia and aspirin. J Pineal Res 23: 79–89, 1997PubMedGoogle Scholar
  28. 28.
    Azekawa T, Sano A, Sei H, Morita Y: Diurnal changes in pineal extracellular indoles of freely moving rats. Neurosci 132: 93–96, 1991Google Scholar
  29. 29.
    Brown AP, Dinger N, Levine BS: Stress produced by gavage administration in the rat. Contemp Top Lab Anim Sci 39: 17–21, 2000PubMedGoogle Scholar
  30. 30.
    Plytycz B, Seljelid R: Rhythms of immunity. Arch Imm Ther Exper 45: 157–162, 1997Google Scholar
  31. 31.
    Reiter RJ, King TS, Steinlechner S, Steger RW, Richardson BA: Tryptophan administration inhibits nocturnal N-acetyltransferase activity and melatonin content in the rat pineal gland. Neuroendocrinology 52: 291–296, 1990PubMedGoogle Scholar
  32. 32.
    Forner MA, Barriga C, Rodríguez AB, Ortega E: A study of the role of corticosterone as a mediator in exercise-induced stimulations of murine macrophage phagocytosis. J Physiol 488: 789–794, 1995PubMedGoogle Scholar
  33. 33.
    Ortega E, Forner MA, Barriga C: Exercise-induced stimulation of murine macrophage chemotaxis. Role of corticosterone and prolactin as mediators. J. Physiol 498: 729–734, 1997PubMedGoogle Scholar
  34. 34.
    Rodríguez AB, Nogales G, Marchena JM, Ortega E, Barriga C: Suppression of both basal and antigen-induced lipid peroxidation in ring dove heterophils by melatonin. Bioch Pharmacol 58: 1301–1306, 1999Google Scholar

Copyright information

© Kluwer Academic Publishers 2004

Authors and Affiliations

  • Susana Esteban
    • 1
  • Cristina Nicolaus
    • 1
  • Antonio Garmundi
    • 1
  • Rubén Victor Rial
    • 1
  • Ana Beatriz Rodríguez
    • 2
  • Eduardo Ortega
    • 2
  • Carmen Barriga Ibars
    • 2
  1. 1.Laboratori de Fisiologia, Departament de Biologia Fonamental i Ciències de la SalutUniversitat de les Illes BalearsSpain
  2. 2.Department of Animal PhysiologyFaculty of Science, University of ExtremaduraSpain

Personalised recommendations