Melatonin biosynthesis and metabolism in peripheral blood mononuclear leucocytes

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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.