Tryptamine serves as a proligand of the AhR transcriptional pathway whose activation is dependent of monoamine oxidases

Mol Endocrinol. 2012 Sep;26(9):1542-51. doi: 10.1210/me.2011-1351. Epub 2012 Aug 3.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Animals
  • Carbazoles / pharmacology
  • Chromatin Immunoprecipitation
  • Cytochrome P-450 CYP1A1 / genetics
  • HT29 Cells
  • Humans
  • Mice
  • Monoamine Oxidase / genetics
  • Monoamine Oxidase / metabolism*
  • Protein Binding
  • RNA Interference
  • Real-Time Polymerase Chain Reaction
  • Receptors, Aryl Hydrocarbon / genetics
  • Receptors, Aryl Hydrocarbon / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics
  • Tryptamines / pharmacology*


  • 6-formylindolo(3,2-b)carbazole
  • Carbazoles
  • Receptors, Aryl Hydrocarbon
  • Tryptamines
  • Cytochrome P-450 CYP1A1
  • Monoamine Oxidase