Melatonin biosynthesis and metabolism in peripheral blood mononuclear leucocytes

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.