Delta9-tetrahydrocannabinol and cannabidiol modulate mitogen-induced tryptophan degradation and neopterin formation in peripheral blood mononuclear cells in vitro.
Nanomolar concentrations of Delta9-tetrahydrocannabinol or cannabidiol are demonstrated to enhance mitogen-induced degradation of tryptophan in human peripheral blood mononuclear cells in dependence of CB1- or CB2-receptor activation. In contrast, suppression of this pathway by cannabinoids in the micromolar concentration range was achieved independent of cannabinoid receptor activation. Both cannabinoids also suppressed tryptophan degradation in myelomonocytic THP-1 cells stimulated with lipopolysaccharide. We conclude, that suppression of tryptophan degradation by cannabinoids via indoleamine-2,3-dioxygenase, which is independent of cannabinoid receptor activation, might enhance the availability of tryptophan for serotonin biosynthesis and consequently can be important in the action of cannabinoids to improve mood disturbances.
Jenny
Marcel
M
Division of Biological Chemistry, Biocenter, Innsbruck Medical University, 6020 Innsbruck, Austria.
Santer
Elisabeth
E
Pirich
Eberhard
E
Schennach
Harald
H
Fuchs
Dietmar
D
D002185:Cannabidiol / Q000494:pharmacology*; D063387:Cannabinoid Receptor Antagonists; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000494:pharmacology*; D004347:Drug Interactions; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D016898:Interferon-alpha / Q000235:genetics / Q000378:metabolism; D007737:Kynurenine / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008934:Mitogens / Q000378:metabolism / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D019798:Neopterin / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D018709:Statistics, Nonparametric; D014364:Tryptophan / Q000378:metabolism*
D063387:Cannabinoid Receptor Antagonists; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007211:Indoles; D016898:Interferon-alpha; D008070:Lipopolysaccharides; D008934:Mitogens; D009025:Morpholines; D011720:Pyrazoles; D002185:Cannabidiol; D007737:Kynurenine; D019798:Neopterin; D013759:Dronabinol; D014364:Tryptophan; C109925:AM 281; C094023:iodopravadoline