Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1991 Dec 15;280(Pt 3):727–731. doi: 10.1042/bj2800727

Melatonin biosynthesis and metabolism in peripheral blood mononuclear leucocytes.

L M Finocchiaro 1, V E Nahmod 1, J M Launay 1
PMCID: PMC1130514  PMID: 1764037

Abstract

Cultured human peripheral blood mononuclear leucocytes (PBML) were able to synthesize indoleamines, including melatonin, and were also able to convert melatonin taken up from the incubation medium into N-acetyl-5-hydroxytryptamine (NAHT) and 5-hydroxytryptamine (5-HT). These compounds were analysed by h.p.l.c., and melatonin was additionally characterized by two-dimensional t.l.c., mass spectrometry and radioimmunoassay. Only hydroxyindoles were detected by h.p.l.c. in unstimulated PBML culture. Sustained stimulation by melatonin or interferon-gamma (IFN-gamma) increased markedly the basal production of 5-HT. IFN-gamma- or 5-HT-stimulated (but not resting) cells produced NAHT and melatonin. Furthermore, the addition of melatonin to the culture medium strongly enhanced NAHT and 5-HT production without affecting tryptophan hydroxylation, suggesting the possibility of direct or indirect transformation of melatonin into NAHT and 5-HT.

Full text

PDF
727

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arzt E. S., Fernández-Castelo S., Finocchiaro L. M., Criscuolo M. E., Díaz A., Finkielman S., Nahmod V. E. Immunomodulation by indoleamines: serotonin and melatonin action on DNA and interferon-gamma synthesis by human peripheral blood mononuclear cells. J Clin Immunol. 1988 Nov;8(6):513–520. doi: 10.1007/BF00916958. [DOI] [PubMed] [Google Scholar]
  2. Beck O., Jonsson G. In vivo formation of 5-methoxytryptamine from melatonin in rat. J Neurochem. 1981 Jun;36(6):2013–2018. doi: 10.1111/j.1471-4159.1981.tb10827.x. [DOI] [PubMed] [Google Scholar]
  3. Bensinger R. E., Klein D. C., Weller J. L., Lovenberg W. Radiometric assay of total tryptophan hydroxylation by intact cultured pineal glands. J Neurochem. 1974 Jul;23(1):111–117. doi: 10.1111/j.1471-4159.1974.tb06923.x. [DOI] [PubMed] [Google Scholar]
  4. Byrne G. I., Lehmann L. K., Kirschbaum J. G., Borden E. C., Lee C. M., Brown R. R. Induction of tryptophan degradation in vitro and in vivo: a gamma-interferon-stimulated activity. J Interferon Res. 1986 Aug;6(4):389–396. doi: 10.1089/jir.1986.6.389. [DOI] [PubMed] [Google Scholar]
  5. Chan A., Ebadi M. Reciprocal relationship between the concentrations of serotonin and the activity of serotonin-N-acetyltransferase in rat pineal glands in culture. Endocr Res Commun. 1981;8(1):25–44. doi: 10.1080/07435808109065981. [DOI] [PubMed] [Google Scholar]
  6. Dedenkov A. N., Raikhlin N. T., Kvetnoi I. M., Kurilets E. S., Balmasova I. P. Immunogistokhimicheskaia i élektronno-mikroskopicheskaia identifikatsiia serotonina, melatonina i beta-éndorfina v granulakh estestvennykh killerov. Biull Eksp Biol Med. 1986 Oct;102(10):491–493. [PubMed] [Google Scholar]
  7. Finocchiaro L. M., Arzt E. S., Fernández-Castelo S., Criscuolo M., Finkielman S., Nahmod V. E. Serotonin and melatonin synthesis in peripheral blood mononuclear cells: stimulation by interferon-gamma as part of an immunomodulatory pathway. J Interferon Res. 1988 Dec;8(6):705–716. doi: 10.1089/jir.1988.8.705. [DOI] [PubMed] [Google Scholar]
  8. Finocchiaro L. M., Scheucher A., Finkielman S., Nahmod V. E., Pirola C. J. Muscarinic effects on the hydroxy- and methoxyindole pathway in the rat pineal gland. J Endocrinol. 1989 Nov;123(2):205–211. doi: 10.1677/joe.0.1230205. [DOI] [PubMed] [Google Scholar]
  9. Finocchiaro L., Callebert J., Launay J. M., Jallon J. M. Melatonin biosynthesis in Drosophila: its nature and its effects. J Neurochem. 1988 Feb;50(2):382–387. doi: 10.1111/j.1471-4159.1988.tb02923.x. [DOI] [PubMed] [Google Scholar]
  10. Fiske V. M., Huppert L. C. Melatonin action on pineal varies with photoperiod. Science. 1968 Oct 11;162(3850):279–279. doi: 10.1126/science.162.3850.279. [DOI] [PubMed] [Google Scholar]
  11. Fraser S., Cowen P., Franklin M., Franey C., Arendt J. Direct radioimmunoassay for melatonin in plasma. Clin Chem. 1983 Feb;29(2):396–397. [PubMed] [Google Scholar]
  12. Hellstrand K., Hermodsson S. Monocyte-mediated suppression of IL-2-induced NK-cell activation. Regulation by 5-HT1A-type serotonin receptors. Scand J Immunol. 1990 Aug;32(2):183–192. doi: 10.1111/j.1365-3083.1990.tb02908.x. [DOI] [PubMed] [Google Scholar]
  13. Hellstrand K., Hermodsson S. Role of serotonin in the regulation of human natural killer cell cytotoxicity. J Immunol. 1987 Aug 1;139(3):869–875. [PubMed] [Google Scholar]
  14. Hirata F., Hayaishi O. New degradative routes of 5-hydroxytryptophan and serotonin by intestinal tryptophan 2,3-dioxygenase. Biochem Biophys Res Commun. 1972 Jun 9;47(5):1112–1119. doi: 10.1016/0006-291x(72)90949-7. [DOI] [PubMed] [Google Scholar]
  15. Hirata F., Hayaishi O., Tokuyama T., Seno S. In vitro and in vivo formation of two new metabolites of melatonin. J Biol Chem. 1974 Feb 25;249(4):1311–1313. [PubMed] [Google Scholar]
  16. Jackson J. C., Cross R. J., Walker R. F., Markesbery W. R., Brooks W. H., Roszman T. L. Influence of serotonin on the immune response. Immunology. 1985 Mar;54(3):505–512. [PMC free article] [PubMed] [Google Scholar]
  17. Launay J. M., Lamaître B. J., Husson H. P., Dreux C., Hartmann L., Da Prada M. Melatonin synthesis by rabbit platelets. Life Sci. 1982 Oct 4;31(14):1487–1494. doi: 10.1016/0024-3205(82)90010-8. [DOI] [PubMed] [Google Scholar]
  18. Leone R. M., Silman R. E. Melatonin can be differentially metabolized in the rat to produce N-acetylserotonin in addition to 6-hydroxy-melatonin. Endocrinology. 1984 May;114(5):1825–1832. doi: 10.1210/endo-114-5-1825. [DOI] [PubMed] [Google Scholar]
  19. Maestroni G. J., Conti A., Pierpaoli W. Role of the pineal gland in immunity: II. Melatonin enhances the antibody response via an opiatergic mechanism. Clin Exp Immunol. 1987 May;68(2):384–391. [PMC free article] [PubMed] [Google Scholar]
  20. Maestroni G. J., Conti A., Pierpaoli W. The pineal gland and the circadian, opiatergic, immunoregulatory role of melatonin. Ann N Y Acad Sci. 1987;496:67–77. doi: 10.1111/j.1749-6632.1987.tb35747.x. [DOI] [PubMed] [Google Scholar]
  21. Ozaki Y., Edelstein M. P., Duch D. S. The actions of interferon and antiinflammatory agents of induction of indoleamine 2,3-dioxygenase in human peripheral blood monocytes. Biochem Biophys Res Commun. 1987 May 14;144(3):1147–1153. doi: 10.1016/0006-291x(87)91431-8. [DOI] [PubMed] [Google Scholar]
  22. Reiter R. J., King T. S., Steinlechner S., Steger R. W., Richardson B. A. Tryptophan administration inhibits nocturnal N-acetyltransferase activity and melatonin content in the rat pineal gland. Evidence that serotonin modulates melatonin production via a receptor-mediated mechanism. Neuroendocrinology. 1990 Sep;52(3):291–296. doi: 10.1159/000125600. [DOI] [PubMed] [Google Scholar]
  23. Schoedon G., Troppmair J., Adolf G., Huber C., Niederwieser A. Interferon-gamma enhances biosynthesis of pterins in peripheral blood mononuclear cells by induction of GTP-cyclohydrolase I activity. J Interferon Res. 1986 Dec;6(6):697–703. doi: 10.1089/jir.1986.6.697. [DOI] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES