Effect of serotonin and related tryptamines on the functional activity of murine phagocytes

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VAŠÍČEK Ondřej ČÍŽ Milan

Rok publikování 2011
Druh Konferenční abstrakty
Citace
Popis Serotonin (5-hydroxytryptamine, 5-HT) is a biogenic monoamine. It is produced by the hydroxylation and decarboxylation of the amino acid tryptophan. The highest concentration of 5-HT in the body (about 95%) is found in the cells of the gastrointestinal tract, of which 90% are within enterochromaffin cells and 10% within enteric neurons. Serotonin is metabolized to N-acetylserotonin (NAS) and then to melatonin (MLT) by the enzymes N-acetyl transferase and 5-hydroxyindole-O-methyltransferase. The aim of the present study was to evaluate the antioxidant properties of 5-HT, NAS and MLT and their effects on functional activity of murine macrophages. Tested tryptamines were used in the concentrations of 10-8M, 10-6M and 10-3M. These cover the concentrations that may occur in the body (10-3M only locally in the areas of inflammation). Non-stimulated murine RAW264.7 macrophages and cells stimulated by lipopolysaccharide (LPS) were cultured with tested tryptamines for 24h and subsequently their chemiluminescence (ROS production) was measured. At the same time, cytokine levels (using commercially available array kit) and NO production (indirectly as the accumulation of nitrites) were measured in the medium medium. iNOS protein expression was measured in lysed cells. Our results showed that 5-HT and NAS were better antioxidants than MLT, which was confirmed by chemiluminescence, TRAP measurements and NO-scavanging evaluation. Production of nitrites and iNOS expression significantly decreased with increasing concentration of tested tryptamines. A significant impact of tested tryptamines on cytokine production in murine macrophages induced by LPS was also proven. It can be concluded that serotonergic system interacts with the immune system, especially with phagocytes. The results suggest that the increase in local concentrations of tryptamines significantly reduces oxidative and nitrative stress.

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