title: Tryptamine serves as a proligand of the AhR transcriptional pathway whose activation is dependent of monoamine oxidases.
abstract: The function of the aryl hydrocarbon receptor (AhR) in mediating the biological effect to environmental pollutants is well established. However, accumulated evidence indicates a wide range of physiological and pathological functions mediated by the AhR, suggesting the existence of endogenous AhR ligand(s). The nature of an AhR ligand remain elusive; however, it is known that the AhR is activated by several compounds, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin or the tryptophan photoproduct 6-formylindolo[3,2-b]carbazole. In this study, we show that physiological concentrations of tryptamine (TA) lead to induction of cytochrome P4501A1 transcription through an AhR-dependent mechanism. In addition, we show that activation of the AhR by TA requires a functional monoamino oxidase system, suggesting that TA acts as an AhR proligand possibly by converting to a high-affinity AhR ligand. Taken together, we show a possible mechanism, through which AhR signaling is activated by endogenous conversion of TA involving monoamine oxidases.
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, SE-14183 Huddinge, Sweden. linda.bergander@ki.se
authors.forename: Linda
authors.initials: L
authors.lastname: Vikström Bergander
authors.forename: Wen
authors.initials: W
authors.lastname: Cai
authors.forename: Bernward
authors.initials: B
authors.lastname: Klocke
authors.forename: Martin
authors.initials: M
authors.lastname: Seifert
authors.forename: Ingemar
authors.initials: I
authors.lastname: Pongratz
mesh_terms: D041721:3T3-L1 Cells; D000818:Animals; D002227:Carbazoles / Q000494:pharmacology; D047369:Chromatin Immunoprecipitation; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D051379:Mice; D008995:Monoamine Oxidase / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D014363:Tryptamines / Q000494:pharmacology*
chemical_list: C111855:6-formylindolo(3,2-b)carbazole; D002227:Carbazoles; D018336:Receptors, Aryl Hydrocarbon; D014363:Tryptamines; D019363:Cytochrome P-450 CYP1A1; D008995:Monoamine Oxidase