Tryptamine CAS 61-54-1

Tryptamine can weakly activate the trace amine related receptor TAAR1 (hTAAR1 in humans). Limited research suggests that tryptamine is a kind of micro neuromodulator, which can regulate the activity of neuronal cell response without binding to relevant postsynaptic receptors.

Tryptamine promotes intestinal peristalsis by activating serotonin receptors in the intestine and increasing colon secretions.

HTAAR1 is a stimulatory G protein coupled receptor (GPCR), which is weakly expressed in the intracellular compartments of presynaptic and postsynaptic neurons. Tryptamine and other hTAAR1 agonists can increase neuronal firing by inhibiting neurotransmitter recycling through cAMP dependent phosphorylation of monoamine reuptake transporters. This mechanism increases the number of neurotransmitters in the synaptic space, and subsequently increases postsynaptic receptor binding and neuronal activation. In contrast, when hTAAR1 co locates with G protein coupled inward rectifier potassium channels (GIRKs), receptor activation promotes membrane hyperpolarization through the outflow of potassium ions to reduce neuronal discharge. The balance between inhibitory and excitatory activities of hTAAR1 activation highlights the role of tryptamine in regulating neural activity.

The activation of hTAAR1 is being studied as a new method to treat depression, addiction and schizophrenia. HTAAR1 is mainly expressed in brain structures related to dopamine system, such as serotonin system in ventral tegmental area (VTA) and dorsal raphe nucleus (DRN). In addition, hTAAR1 gene is located on 6q23.2 of human chromosome, which is the susceptible locus of emotional disorders and schizophrenia. The activation of TAAR1 indicates a potential therapeutic approach for neuropsychiatric diseases, because TAAR1 agonists produce antidepressant activity, increased cognition, reduced stress and anti addiction effects.

The tryptamine produced by symbiotic bacteria in the human intestine activates the serotonin GPCR, which is commonly expressed in colon epithelial cells. After tryptamine binding, the conformation of activated 5-HT 4 receptor changes, allowing its G s α Subunits exchange GDP to GTP, and βγ The subunits are released. GTP binding Gs activate adenylate cyclase, which catalyzes the conversion of ATP to cyclic adenosine monophosphate (cAMP). CAMP opens chloride and potassium channels to drive colonic electrolyte secretion and promote intestinal peristalsis.